Trial Outcomes & Findings for A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Prophylactic Emicizumab Versus no Prophylaxis in Hemophilia A Participants With Inhibitors (NCT NCT02622321)

NCT ID: NCT02622321

Last Updated: 2021-06-24

Results Overview

The number of treated bleeds over the efficacy period was assessed as an annualized bleed rate (ABR) using a negative binomial (NB) regression model, which accounts for different follow-up times. Treated bleeds were defined as a bleed that was directly followed by a hemophilia medication reported to be a "treatment for bleed". The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 113 participants
• Primary outcome timeframe: From Baseline up to 24 weeks (median [min-max] efficacy observation periods in Arm A vs. Arm B: 29.29 [0.1-48.9] weeks vs. 24.14 [23.0-26.0] weeks)
• Results posted on: 2021-06-24

Participant Flow

A total of 113 participants were enrolled in this study: 109 participants prior to the primary completion date plus a further 4 participants to Arm D of the study after the primary completion date. Participants in Arm A and Arm B were randomized in a 2:1 ratio; participants in Arm C and Arm D were enrolled without randomization.

Participant milestones

Measure	Arm A: 1.5 mg/kg Emicizumab QW Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis, Then Emicizumab Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm C: 1.5 mg/kg Emicizumab QW Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm D: 1.5 mg/kg Emicizumab QW Participants who were either: 1) Receiving episodic bypassing agents prior to study entry but were unable to enroll in Arms A or B; or 2) Receiving bypassing agent prophylaxis prior to study entry but were unable to enroll in Arm C, were enrolled in Arm D to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.
Overall Study STARTED	35	18	49	11
Overall Study Received at Least One Dose of Treatment	34	18	49	11
Overall Study Completed 24 Weeks in the Study	31	18	49	11
Overall Study Dose Up-Titrated to 3 mg/kg QW	2	0	3	2
Overall Study COMPLETED	32	18	48	11
Overall Study NOT COMPLETED	3	0	1	0

Reasons for withdrawal

Measure	Arm A: 1.5 mg/kg Emicizumab QW Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis, Then Emicizumab Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm C: 1.5 mg/kg Emicizumab QW Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm D: 1.5 mg/kg Emicizumab QW Participants who were either: 1) Receiving episodic bypassing agents prior to study entry but were unable to enroll in Arms A or B; or 2) Receiving bypassing agent prophylaxis prior to study entry but were unable to enroll in Arm C, were enrolled in Arm D to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.
Overall Study Withdrawal by Subject	2	0	0	0
Overall Study Death	0	0	1	0
Overall Study Physician Decision	1	0	0	0

Baseline Characteristics

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Prophylactic Emicizumab Versus no Prophylaxis in Hemophilia A Participants With Inhibitors

Baseline characteristics by cohort

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=35 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis, Then Emicizumab n=18 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm C: 1.5 mg/kg Emicizumab QW n=49 Participants Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm D: 1.5 mg/kg Emicizumab QW n=11 Participants Participants who were either: 1) Receiving episodic bypassing agents prior to study entry but were unable to enroll in Arms A or B; or 2) Receiving bypassing agent prophylaxis prior to study entry but were unable to enroll in Arm C, were enrolled in Arm D to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Total n=113 Participants Total of all reporting groups
Age, Continuous	35.8 years STANDARD_DEVIATION 13.9 • n=5 Participants	37.2 years STANDARD_DEVIATION 13.7 • n=7 Participants	25.6 years STANDARD_DEVIATION 16.8 • n=5 Participants	39.0 years STANDARD_DEVIATION 16.1 • n=4 Participants	31.9 years STANDARD_DEVIATION 16.2 • n=21 Participants
Age, Customized Adolescents (12-17 years)	4 Participants n=5 Participants	2 Participants n=7 Participants	26 Participants n=5 Participants	0 Participants n=4 Participants	32 Participants n=21 Participants
Age, Customized Adults (18-64 years)	30 Participants n=5 Participants	15 Participants n=7 Participants	21 Participants n=5 Participants	10 Participants n=4 Participants	76 Participants n=21 Participants
Age, Customized Elderly (65-84 years)	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Sex: Female, Male Male	35 Participants n=5 Participants	18 Participants n=7 Participants	49 Participants n=5 Participants	11 Participants n=4 Participants	113 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	1 Participants n=7 Participants	12 Participants n=5 Participants	1 Participants n=4 Participants	18 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	31 Participants n=5 Participants	17 Participants n=7 Participants	37 Participants n=5 Participants	10 Participants n=4 Participants	95 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Asian	10 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants	0 Participants n=4 Participants	21 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	0 Participants n=4 Participants	11 Participants n=21 Participants
Race (NIH/OMB) White	21 Participants n=5 Participants	10 Participants n=7 Participants	33 Participants n=5 Participants	11 Participants n=4 Participants	75 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants	0 Participants n=4 Participants	4 Participants n=21 Participants
Number of Participants by the Number of Bleeds (<9 or ≥9) in the Last 24 Weeks Prior to Study Entry <9 Bleeds	11 Participants n=5 Participants	5 Participants n=7 Participants	23 Participants n=5 Participants	6 Participants n=4 Participants	45 Participants n=21 Participants
Number of Participants by the Number of Bleeds (<9 or ≥9) in the Last 24 Weeks Prior to Study Entry ≥9 Bleeds	24 Participants n=5 Participants	13 Participants n=7 Participants	26 Participants n=5 Participants	5 Participants n=4 Participants	68 Participants n=21 Participants

PRIMARY outcome

Timeframe: From Baseline up to 24 weeks (median [min-max] efficacy observation periods in Arm A vs. Arm B: 29.29 [0.1-48.9] weeks vs. 24.14 [23.0-26.0] weeks)

Population: Intent-to-treat (ITT) population defined as all participants who were randomized to Arm A or Arm B.

The number of treated bleeds over the efficacy period was assessed as an annualized bleed rate (ABR) using a negative binomial (NB) regression model, which accounts for different follow-up times. Treated bleeds were defined as a bleed that was directly followed by a hemophilia medication reported to be a "treatment for bleed". The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose.

Outcome measures

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=35 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis n=18 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Emi): 1.5 mg/kg Emicizumab QW This arm includes Arm B participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. After Week 24, emicizumab was administered at a loading dose of 3 mg/kg once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study.	Arm C: 1.5 mg/kg Emicizumab QW Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	All Participants: 1.5 mg/kg Emicizumab QW This analysis set included all enrolled participants on the study. For Arm B, it only all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Participants continued to receive bypassing agent therapy to treat breakthrough bleeds, with rFVIIa and/or aPCC.
Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis	2.9 treated bleeds per year Interval 1.69 to 5.02	23.3 treated bleeds per year Interval 12.33 to 43.89	—	—	—

SECONDARY outcome

Timeframe: From Baseline up to 24 weeks (median [min-max] efficacy observation periods in Arm A vs. Arm B: 29.29 [0.1-48.9] weeks vs. 24.14 [23.0-26.0] weeks)

Population: ITT population: all participants who were randomized to Arm A or Arm B.

The number of all bleeds over the efficacy period was assessed as an annualized bleed rate (ABR) using a negative binomial (NB) regression model, which accounts for different follow-up times. All bleeds included both treated bleeds (with coagulation factors) and non-treated bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose.

Outcome measures

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=35 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis n=18 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Emi): 1.5 mg/kg Emicizumab QW This arm includes Arm B participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. After Week 24, emicizumab was administered at a loading dose of 3 mg/kg once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study.	Arm C: 1.5 mg/kg Emicizumab QW Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	All Participants: 1.5 mg/kg Emicizumab QW This analysis set included all enrolled participants on the study. For Arm B, it only all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Participants continued to receive bypassing agent therapy to treat breakthrough bleeds, with rFVIIa and/or aPCC.
Model-Based Annualized Bleed Rate (ABR) for All Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis	5.5 all bleeds per year Interval 3.58 to 8.6	28.3 all bleeds per year Interval 16.79 to 47.76	—	—	—

SECONDARY outcome

Timeframe: Median [min-max] efficacy observation periods: for Arm A, 1.5 mg/kg Emicizumab QW: 30.86 [0.1-48.9] weeks; for Arm A (NIS), Previous Episodic Bypassing Agents: 21.14 [10.6-33.9] weeks

Population: Arm A NIS population included all Arm A participants who participated in NIS BH29768 before study entry and received episodic bypassing agents during NIS BH29768.

This was an intra-participant comparison of the annualized bleed rates (ABRs) for all bleeds in Arm A participants who had previously received episodic bypassing agents during the non-interventional study (NIS) BH29768 (NCT02476942) (Arm A NIS) prior to entry in this study versus emicizumab prophylaxis during this study (Arm A). The number of all bleeds over the efficacy period was assessed as an ABR using a negative binomial (NB) regression model, which accounts for different follow-up times. All bleeds included both treated bleeds (with coagulation factors) and non-treated bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose.

Outcome measures

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=24 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis n=24 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Emi): 1.5 mg/kg Emicizumab QW This arm includes Arm B participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. After Week 24, emicizumab was administered at a loading dose of 3 mg/kg once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study.	Arm C: 1.5 mg/kg Emicizumab QW Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	All Participants: 1.5 mg/kg Emicizumab QW This analysis set included all enrolled participants on the study. For Arm B, it only all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Participants continued to receive bypassing agent therapy to treat breakthrough bleeds, with rFVIIa and/or aPCC.
Intra-Participant Comparison of the Model-Based Annualized Bleed Rate (ABR) for All Bleeds in Arm A: Emicizumab Versus Previous Episodic Bypassing Agents	4.1 all bleeds per year Interval 2.1 to 8.02	37.7 all bleeds per year Interval 28.4 to 50.04	—	—	—

SECONDARY outcome

Timeframe: Median [min-max] efficacy observation periods: for Arm A, 1.5 mg/kg Emicizumab QW: 30.86 [0.1-48.9] weeks; for Arm A (NIS), Previous Episodic Bypassing Agents: 21.14 [10.6-33.9] weeks

Population: Arm A NIS population included all Arm A participants who participated in NIS BH29768 before study entry and received episodic bypassing agents during NIS BH29768.

This was an intra-participant comparison of the ABRs for treated bleeds in Arm A participants who had previously received episodic bypassing agents during the non-interventional study (NIS) BH29768 (NCT02476942) (Arm A NIS) prior to entry in this study versus emicizumab prophylaxis during this study (Arm A). The number of treated bleeds over the efficacy period was assessed as an ABR using a negative binomial (NB) regression model, which accounts for different follow-up times. Treated bleeds were defined as a bleed that was directly followed by a hemophilia medication reported to be a "treatment for bleed". The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, efficacy period ended the day before the first day on the up-titrated dose.

Outcome measures

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=24 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis n=24 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Emi): 1.5 mg/kg Emicizumab QW This arm includes Arm B participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. After Week 24, emicizumab was administered at a loading dose of 3 mg/kg once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study.	Arm C: 1.5 mg/kg Emicizumab QW Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	All Participants: 1.5 mg/kg Emicizumab QW This analysis set included all enrolled participants on the study. For Arm B, it only all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Participants continued to receive bypassing agent therapy to treat breakthrough bleeds, with rFVIIa and/or aPCC.
Intra-Participant Comparison of the Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds in Arm A: Emicizumab Versus Previous Episodic Bypassing Agents	1.7 treated bleeds per year Interval 0.71 to 4.06	21.6 treated bleeds per year Interval 15.4 to 30.22	—	—	—

SECONDARY outcome

Timeframe: From Baseline up to 24 weeks (median [min-max] efficacy observation periods in Arm A vs. Arm B: 29.29 [0.1-48.9] weeks vs. 24.14 [23.0-26.0] weeks)

Population: ITT population: all participants who were randomized to Arm A or Arm B.

The number of treated joint bleeds over the efficacy period was assessed as an ABR using a negative binomial (NB) regression model, which accounts for different follow-up times. Treated joint bleeds were defined as treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Bleeds due to surgery/procedure were excluded.

Outcome measures

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=35 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis n=18 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Emi): 1.5 mg/kg Emicizumab QW This arm includes Arm B participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. After Week 24, emicizumab was administered at a loading dose of 3 mg/kg once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study.	Arm C: 1.5 mg/kg Emicizumab QW Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	All Participants: 1.5 mg/kg Emicizumab QW This analysis set included all enrolled participants on the study. For Arm B, it only all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Participants continued to receive bypassing agent therapy to treat breakthrough bleeds, with rFVIIa and/or aPCC.
Model-Based Annualized Bleed Rate (ABR) for Treated Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis	0.8 treated joint bleeds per year Interval 0.26 to 2.2	6.7 treated joint bleeds per year Interval 1.99 to 22.42	—	—	—

SECONDARY outcome

Timeframe: Median [min-max] efficacy observation periods: for Arm C, 1.5 mg/kg Emicizumab QW: 30.14 [6.9-45.3] weeks; for Arm C (NIS), Previous Prophylactic Bypassing Agents: 32.14 [8.1-49.3] weeks

Population: Arm C NIS population included all Arm C participants who participated in NIS BH29768 before study entry and received prophylactic bypassing agents during NIS BH29768.

This was an intra-participant comparison of the annualized bleed rates (ABRs) for all bleeds in Arm C participants who had previously received prophylactic bypassing agents during the non-interventional study (NIS) BH29768 (NCT02476942) (Arm C NIS) prior to entry in this study versus emicizumab prophylaxis during this study (Arm C). The number of all bleeds over the efficacy period was assessed as an ABR using a negative binomial (NB) regression model, which accounts for different follow-up times. All bleeds included both treated bleeds (with coagulation factors) and non-treated bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose.

Outcome measures

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=24 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis n=24 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Emi): 1.5 mg/kg Emicizumab QW This arm includes Arm B participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. After Week 24, emicizumab was administered at a loading dose of 3 mg/kg once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study.	Arm C: 1.5 mg/kg Emicizumab QW Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	All Participants: 1.5 mg/kg Emicizumab QW This analysis set included all enrolled participants on the study. For Arm B, it only all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Participants continued to receive bypassing agent therapy to treat breakthrough bleeds, with rFVIIa and/or aPCC.
Intra-Participant Comparison of the Model-Based Annualized Bleed Rate (ABR) for All Bleeds in Arm C: Emicizumab Versus Previous Prophylactic Bypassing Agents	5.5 all bleeds per year Interval 2.98 to 10.26	24.3 all bleeds per year Interval 18.11 to 32.67	—	—	—

SECONDARY outcome

Timeframe: Median [min-max] efficacy observation periods: for Arm C, 1.5 mg/kg Emicizumab QW: 30.14 [6.9-45.3] weeks; for Arm C (NIS), Previous Prophylactic Bypassing Agents: 32.14 [8.1-49.3] weeks

Population: Arm C NIS population included all Arm C participants who participated in NIS BH29768 before study entry and received prophylactic bypassing agents during NIS BH29768.

This was an intra-participant comparison of the ABRs for treated bleeds in Arm C participants who had previously received bypassing agent prophylaxis during the non-interventional study (NIS) BH29768 (NCT02476942) (Arm C NIS) prior to entry in this study versus emicizumab prophylaxis during this study (Arm C). The number of treated bleeds over the efficacy period was assessed as an ABR using a negative binomial (NB) regression model, which accounts for different follow-up times. Treated bleeds were defined as a bleed that was directly followed by a hemophilia medication reported to be a "treatment for bleed". The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, efficacy period ended the day before the first day on the up-titrated dose.

Outcome measures

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=24 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis n=24 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Emi): 1.5 mg/kg Emicizumab QW This arm includes Arm B participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. After Week 24, emicizumab was administered at a loading dose of 3 mg/kg once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study.	Arm C: 1.5 mg/kg Emicizumab QW Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	All Participants: 1.5 mg/kg Emicizumab QW This analysis set included all enrolled participants on the study. For Arm B, it only all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Participants continued to receive bypassing agent therapy to treat breakthrough bleeds, with rFVIIa and/or aPCC.
Intra-Participant Comparison of the Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds in Arm C: Emicizumab Versus Previous Prophylactic Bypassing Agents	3.3 treated bleeds per year Interval 1.33 to 8.08	15.7 treated bleeds per year Interval 11.08 to 22.29	—	—	—

SECONDARY outcome

Timeframe: From Baseline up to 24 weeks (median [min-max] efficacy observation periods in Arm A vs. Arm B: 29.29 [0.1-48.9] weeks vs. 24.14 [23.0-26.0] weeks)

Population: ITT population: all participants who were randomized to Arm A or Arm B.

The number of treated spontaneous bleeds over the efficacy period was assessed as an annualized bleed rate (ABR) using a negative binomial (NB) regression model, which accounts for different follow-up times. Treated spontaneous bleeds were defined as treated (with coagulation factors) bleeds with no known contributing factor (e.g., trauma, surgery). The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose.

Outcome measures

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=35 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis n=18 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Emi): 1.5 mg/kg Emicizumab QW This arm includes Arm B participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. After Week 24, emicizumab was administered at a loading dose of 3 mg/kg once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study.	Arm C: 1.5 mg/kg Emicizumab QW Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	All Participants: 1.5 mg/kg Emicizumab QW This analysis set included all enrolled participants on the study. For Arm B, it only all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Participants continued to receive bypassing agent therapy to treat breakthrough bleeds, with rFVIIa and/or aPCC.
Model-Based Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis	1.3 treated spontaneous bleeds per year Interval 0.73 to 2.19	16.8 treated spontaneous bleeds per year Interval 9.94 to 28.3	—	—	—

SECONDARY outcome

Timeframe: From Baseline up to 24 weeks (median [min-max] efficacy observation periods in Arm A vs. Arm B: 29.29 [0.1-48.9] weeks vs. 24.14 [23.0-26.0] weeks)

Population: ITT population: all participants who were randomized to Arm A or Arm B.

The number of treated target joint bleeds over the efficacy period was assessed as an annualized bleed rate (ABR) using a negative binomial (NB) regression model, which accounts for different follow-up times. Treated target joint bleeds included treated (with coagulation factors) joint bleeds in a target joint, defined as a joint in which greater than or equal to (>/=) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose.

Outcome measures

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=35 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis n=18 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Emi): 1.5 mg/kg Emicizumab QW This arm includes Arm B participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. After Week 24, emicizumab was administered at a loading dose of 3 mg/kg once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study.	Arm C: 1.5 mg/kg Emicizumab QW Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	All Participants: 1.5 mg/kg Emicizumab QW This analysis set included all enrolled participants on the study. For Arm B, it only all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Participants continued to receive bypassing agent therapy to treat breakthrough bleeds, with rFVIIa and/or aPCC.
Model-Based Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis	0.1 treated target joint bleeds per year Interval 0.03 to 0.58	3.0 treated target joint bleeds per year Interval 0.96 to 9.13	—	—	—

SECONDARY outcome

Timeframe: From Baseline up to 24 weeks (median [min-max] efficacy observation periods in Arm A vs. Arm B: 29.29 [0.1-48.9] weeks vs. 24.14 [23.0-26.0] weeks)

Population: ITT population: all participants who were randomized to Arm A or Arm B.

The number of bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (>/=) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration were excluded.

Outcome measures

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=35 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis n=18 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Emi): 1.5 mg/kg Emicizumab QW This arm includes Arm B participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. After Week 24, emicizumab was administered at a loading dose of 3 mg/kg once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study.	Arm C: 1.5 mg/kg Emicizumab QW Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	All Participants: 1.5 mg/kg Emicizumab QW This analysis set included all enrolled participants on the study. For Arm B, it only all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Participants continued to receive bypassing agent therapy to treat breakthrough bleeds, with rFVIIa and/or aPCC.
Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis Treated Bleeds	3.5 bleeds per year Interval 0.83 to 9.46	26.2 bleeds per year Interval 17.17 to 38.37	—	—	—
Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis All Bleeds	6.3 bleeds per year Interval 2.37 to 13.45	30.8 bleeds per year Interval 20.89 to 43.76	—	—	—
Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis Treated Spontaneous Bleeds	1.5 bleeds per year Interval 0.11 to 6.42	18.1 bleeds per year Interval 10.74 to 28.57	—	—	—
Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis Treated Joint Bleeds	1.0 bleeds per year Interval 0.03 to 5.57	8.1 bleeds per year Interval 3.55 to 15.95	—	—	—
Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis Treated Target Joint Bleeds	0.4 bleeds per year Interval 0.0 to 4.48	6.2 bleeds per year Interval 2.32 to 13.34	—	—	—

SECONDARY outcome

Timeframe: From Baseline up to 24 weeks (median [min-max] efficacy observation periods in Arm A vs. Arm B: 29.29 [0.1-48.9] weeks vs. 24.14 [23.0-26.0] weeks)

Population: ITT population: all participants who were randomized to Arm A or Arm B.

The number of bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (>/=) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration were excluded.

Outcome measures

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=35 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis n=18 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Emi): 1.5 mg/kg Emicizumab QW This arm includes Arm B participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. After Week 24, emicizumab was administered at a loading dose of 3 mg/kg once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study.	Arm C: 1.5 mg/kg Emicizumab QW Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	All Participants: 1.5 mg/kg Emicizumab QW This analysis set included all enrolled participants on the study. For Arm B, it only all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Participants continued to receive bypassing agent therapy to treat breakthrough bleeds, with rFVIIa and/or aPCC.
Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis Treated Bleeds	0.0 bleeds per year Interval 0.0 to 3.73	18.8 bleeds per year Interval 12.97 to 35.08	—	—	—
Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis All Bleeds	2.0 bleeds per year Interval 0.0 to 9.87	30.2 bleeds per year Interval 18.26 to 39.37	—	—	—
Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis Treated Spontaneous Bleeds	0.0 bleeds per year Interval 0.0 to 3.28	15.2 bleeds per year Interval 6.64 to 30.44	—	—	—
Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis Treated Joint Bleeds	0.0 bleeds per year Interval 0.0 to 0.0	1.0 bleeds per year Interval 0.0 to 14.44	—	—	—
Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis Treated Target Joint Bleeds	0.0 bleeds per year Interval 0.0 to 0.0	1.0 bleeds per year Interval 0.0 to 6.52	—	—	—

SECONDARY outcome

Timeframe: From Baseline up to 24 weeks (median [min-max] efficacy observation periods in Arm A vs. Arm B: 29.29 [0.1-48.9] weeks vs. 24.14 [23.0-26.0] weeks)

Population: ITT population: all participants who were randomized to Arm A or Arm B.

Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (>/=) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration were excluded.

Outcome measures

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=35 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis n=18 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Emi): 1.5 mg/kg Emicizumab QW This arm includes Arm B participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. After Week 24, emicizumab was administered at a loading dose of 3 mg/kg once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study.	Arm C: 1.5 mg/kg Emicizumab QW Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	All Participants: 1.5 mg/kg Emicizumab QW This analysis set included all enrolled participants on the study. For Arm B, it only all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Participants continued to receive bypassing agent therapy to treat breakthrough bleeds, with rFVIIa and/or aPCC.
Percentage of Participants With 0 Bleeds for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis All Bleeds	37.1 Percentage of participants Interval 21.5 to 55.1	5.6 Percentage of participants Interval 0.1 to 27.3	—	—	—
Percentage of Participants With 0 Bleeds for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis Treated Bleeds	62.9 Percentage of participants Interval 44.9 to 78.5	5.6 Percentage of participants Interval 0.1 to 27.3	—	—	—
Percentage of Participants With 0 Bleeds for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis Treated Spontaneous Bleeds	68.6 Percentage of participants Interval 50.7 to 83.1	11.1 Percentage of participants Interval 1.4 to 34.7	—	—	—
Percentage of Participants With 0 Bleeds for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis Treated Joint Bleeds	85.7 Percentage of participants Interval 69.7 to 95.2	50.0 Percentage of participants Interval 26.0 to 74.0	—	—	—
Percentage of Participants With 0 Bleeds for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, Arm A: Emicizumab Versus Arm B: No Prophylaxis Treated Target Joint Bleeds	94.3 Percentage of participants Interval 80.8 to 99.3	50.0 Percentage of participants Interval 26.0 to 74.0	—	—	—

SECONDARY outcome

Timeframe: Week 25

Population: ITT population: all participants who were randomized to Arm A or Arm B. The number of participants analyzed is the number of adult participants (≥18 years old) in Arms A and B who responded to the questionnaire at Week 25.

Haem-A-QoL questionnaire has been developed and used in hemophilia A participants. As a hemophilia-specific questionnaire, this measure assesses very specific aspects of dealing with hemophilia. This questionnaire consists of items pertaining to 10 domains specific to living with hemophilia. The 10 domains are: physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feeling, relationships, treatment, view of yourself, and outlook for the future. The total score for each domain range from 0 to 100 with lower scores reflective of better quality of life. Physical Health domain score is reported (range 0 to 100, with lower scores reflective of better physical health).

Outcome measures

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=26 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis n=14 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Emi): 1.5 mg/kg Emicizumab QW This arm includes Arm B participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. After Week 24, emicizumab was administered at a loading dose of 3 mg/kg once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study.	Arm C: 1.5 mg/kg Emicizumab QW Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	All Participants: 1.5 mg/kg Emicizumab QW This analysis set included all enrolled participants on the study. For Arm B, it only all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Participants continued to receive bypassing agent therapy to treat breakthrough bleeds, with rFVIIa and/or aPCC.
Hemophilia-Specific Quality of Life (Haem-A-QoL) Questionnaire Physical Health Score at Week 25 in Adult Participants (>/=18 Years Old), Arm A: Emicizumab Versus Arm B: No Prophylaxis	30.19 score on a scale Standard Deviation 26.59	57.14 score on a scale Standard Deviation 23.35	—	—	—

SECONDARY outcome

Timeframe: Week 25

Population: ITT population: all participants who were randomized to Arm A or Arm B. The number of participants analyzed is the number of adult participants (≥18 years old) in Arms A and B who responded to the questionnaire at Week 25.

Haem-A-QoL questionnaire has been developed and used in hemophilia A participants. As a hemophilia-specific questionnaire, this measure assesses very specific aspects of dealing with hemophilia. This questionnaire consists of items pertaining to 10 domains specific to living with hemophilia. The 10 domains are: physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feeling, relationships, treatment, view of yourself, and outlook for the future. The total score for each domain range from 0 to 100 with lower scores reflective of better quality of life. Haem-A-QoL Questionnaire Total Score is the average of the all domain scores and range from 0 to 100, with lower scores reflective of better quality of life.

Outcome measures

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=26 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis n=14 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Emi): 1.5 mg/kg Emicizumab QW This arm includes Arm B participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. After Week 24, emicizumab was administered at a loading dose of 3 mg/kg once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study.	Arm C: 1.5 mg/kg Emicizumab QW Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	All Participants: 1.5 mg/kg Emicizumab QW This analysis set included all enrolled participants on the study. For Arm B, it only all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Participants continued to receive bypassing agent therapy to treat breakthrough bleeds, with rFVIIa and/or aPCC.
Haem-A-QoL Questionnaire Total Score at Week 25 in Adult Participants (>/=18 Years Old), Arm A: Emicizumab Versus Arm B: No Prophylaxis	26.465 score on a scale Standard Deviation 18.666	47.504 score on a scale Standard Deviation 17.435	—	—	—

SECONDARY outcome

Timeframe: Week 25

Population: ITT population: all participants who were randomized to Arm A or Arm B. The number of participants analyzed is the number of participants in Arms A and B who responded to the questionnaire at Week 25.

EQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state profile (descriptive system) and the EQ-5D-5L Visual Analog Scale. The Visual Analogue Scale is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.

Outcome measures

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=30 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis n=16 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Emi): 1.5 mg/kg Emicizumab QW This arm includes Arm B participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. After Week 24, emicizumab was administered at a loading dose of 3 mg/kg once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study.	Arm C: 1.5 mg/kg Emicizumab QW Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	All Participants: 1.5 mg/kg Emicizumab QW This analysis set included all enrolled participants on the study. For Arm B, it only all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Participants continued to receive bypassing agent therapy to treat breakthrough bleeds, with rFVIIa and/or aPCC.
European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale Score at Week 25, Arm A: Emicizumab Versus Arm B: No Prophylaxis	83.8 score on a scale Standard Deviation 12.9	76.4 score on a scale Standard Deviation 15.7	—	—	—

SECONDARY outcome

Timeframe: Week 25

Population: ITT population: all participants who were randomized to Arm A or Arm B. The number of participants analyzed is the number of participants in Arms A and B who responded to the questionnaire at Week 25.

EQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state profile (descriptive system) and the EQ-5D-5L Visual Analog Scale. The EQ-5D-5L health state profile is designed to record the participant's current health state in 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Responses from the five domains are used to calculate a single utility index value ranging from 1 to 5, where 1 indicates better health state (no problems) and 5 indicates worst health state (confined to bed).

Outcome measures

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=30 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis n=16 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Emi): 1.5 mg/kg Emicizumab QW This arm includes Arm B participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. After Week 24, emicizumab was administered at a loading dose of 3 mg/kg once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study.	Arm C: 1.5 mg/kg Emicizumab QW Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	All Participants: 1.5 mg/kg Emicizumab QW This analysis set included all enrolled participants on the study. For Arm B, it only all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Participants continued to receive bypassing agent therapy to treat breakthrough bleeds, with rFVIIa and/or aPCC.
EQ-5D-5L Index Utility Score at Week 25, Arm A: Emicizumab Versus Arm B: No Prophylaxis	0.83 score on a scale Standard Deviation 0.22	0.60 score on a scale Standard Deviation 0.35	—	—	—

SECONDARY outcome

Timeframe: Baseline and Week 25 (for Arm B (Emi), Study Weeks are relative to first emicizumab dose)

Population: The number analyzed is the number of adolescent participants (12-17 years old) who responded to the questionnaire at baseline and Week 25. Arm D is excluded because no adolescents were enrolled in that arm.

The Haemo-QoL-SF contains 35 items, which cover nine domains considered relevant for the children's health-related quality of life (physical health, feelings, view of yourself, family, friends, other people, sports and school, dealing with hemophilia and treatment). Items are rated with five respective response options: never, seldom, sometimes, often, and always. Haemo-QoL-SF total score range from 0 to 100, where lower scores reflect better health-related quality of life. Baseline was defined as the last assessment prior to treatment. Because participants in Arm B switched from episodic bypassing agents to start receiving emicizumab prophylaxis after Week 24, the timepoints for Arm B (Emi) are expressed relative to first emicizumab dose; baseline for Arm B (Emi) is the same as Week 25 for Arm B (Control).

Outcome measures

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=4 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis n=2 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Emi): 1.5 mg/kg Emicizumab QW n=2 Participants This arm includes Arm B participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. After Week 24, emicizumab was administered at a loading dose of 3 mg/kg once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study.	Arm C: 1.5 mg/kg Emicizumab QW n=26 Participants Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	All Participants: 1.5 mg/kg Emicizumab QW This analysis set included all enrolled participants on the study. For Arm B, it only all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Participants continued to receive bypassing agent therapy to treat breakthrough bleeds, with rFVIIa and/or aPCC.
Hemophilia-Specific Quality of Life - Short Form (Haemo-Qol-SF) Questionnaire Total Score at Baseline and Week 25 in Adolescent Participants (12-17 Years Old) Baseline	34.643 units on a scale Standard Deviation 22.728	37.143 units on a scale Standard Deviation 12.122	30.000 units on a scale Standard Deviation 14.142	30.714 units on a scale Standard Deviation 15.625	—
Hemophilia-Specific Quality of Life - Short Form (Haemo-Qol-SF) Questionnaire Total Score at Baseline and Week 25 in Adolescent Participants (12-17 Years Old) Week 25	33.095 units on a scale Standard Deviation 17.559	30.000 units on a scale Standard Deviation 14.142	12.143 units on a scale Standard Deviation 7.071	19.286 units on a scale Standard Deviation 14.507	—

SECONDARY outcome

Timeframe: From start of emicizumab treatment to study completion (median [min-max] efficacy observation period for all participants: 109.29 [0.1-249.1] weeks)

Population: All enrolled participants; for Arm B, it only includes participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis.

The number of bleeds over the efficacy period was assessed as an ABR using a negative binomial (NB) regression model, which accounts for different follow-up times. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (>/=) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration were excluded.

Outcome measures

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=35 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis n=18 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Emi): 1.5 mg/kg Emicizumab QW n=49 Participants This arm includes Arm B participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. After Week 24, emicizumab was administered at a loading dose of 3 mg/kg once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study.	Arm C: 1.5 mg/kg Emicizumab QW n=11 Participants Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	All Participants: 1.5 mg/kg Emicizumab QW n=113 Participants This analysis set included all enrolled participants on the study. For Arm B, it only all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Participants continued to receive bypassing agent therapy to treat breakthrough bleeds, with rFVIIa and/or aPCC.
Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants Treated Bleeds	1.9 bleeds per year Interval 1.02 to 3.53	0.6 bleeds per year Interval 0.22 to 1.36	3.2 bleeds per year Interval 1.51 to 6.65	1.5 bleeds per year Interval 0.2 to 11.72	2.4 bleeds per year Interval 1.5 to 3.82
Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants All Bleeds	3.5 bleeds per year Interval 2.11 to 5.74	1.3 bleeds per year Interval 0.66 to 2.39	4.3 bleeds per year Interval 2.43 to 7.77	2.3 bleeds per year Interval 0.79 to 6.77	3.6 bleeds per year Interval 2.55 to 5.13
Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants Treated Spontaneous Bleeds	0.6 bleeds per year Interval 0.33 to 1.26	0.1 bleeds per year Interval 0.06 to 0.29	2.1 bleeds per year Interval 0.89 to 4.8	0.8 bleeds per year Interval 0.07 to 9.16	1.3 bleeds per year Interval 0.76 to 2.18
Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants Treated Joint Bleeds	0.5 bleeds per year Interval 0.16 to 1.69	0.1 bleeds per year Interval 0.04 to 0.31	0.4 bleeds per year Interval 0.14 to 0.96	0.4 bleeds per year Interval 0.05 to 3.41	0.4 bleeds per year Interval 0.21 to 0.82
Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants Treated Target Joint Bleeds	0.1 bleeds per year Interval 0.01 to 0.31	0.01 bleeds per year Interval 0.01 to 0.18	0.3 bleeds per year Interval 0.09 to 0.84	0.3 bleeds per year Interval 0.04 to 2.36	0.2 bleeds per year Interval 0.1 to 0.57

SECONDARY outcome

Timeframe: From start of emicizumab treatment to study completion (median [min-max] efficacy observation period for all participants: 109.29 [0.1-249.1] weeks)

Population: All enrolled participants; for Arm B, it only includes participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis.

The number of bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (>/=) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration were excluded.

Outcome measures

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=35 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis n=18 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Emi): 1.5 mg/kg Emicizumab QW n=49 Participants This arm includes Arm B participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. After Week 24, emicizumab was administered at a loading dose of 3 mg/kg once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study.	Arm C: 1.5 mg/kg Emicizumab QW n=11 Participants Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	All Participants: 1.5 mg/kg Emicizumab QW n=113 Participants This analysis set included all enrolled participants on the study. For Arm B, it only all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Participants continued to receive bypassing agent therapy to treat breakthrough bleeds, with rFVIIa and/or aPCC.
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants Treated Bleeds	2.9 bleeds per year Interval 0.58 to 8.63	0.6 bleeds per year Interval 0.0 to 4.85	3.3 bleeds per year Interval 0.77 to 9.28	1.6 bleeds per year Interval 0.14 to 6.61	2.6 bleeds per year Interval 0.46 to 8.16
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants All Bleeds	4.8 bleeds per year Interval 1.49 to 11.33	1.3 bleeds per year Interval 0.07 to 6.11	4.6 bleeds per year Interval 1.4 to 11.09	2.5 bleeds per year Interval 0.42 to 8.02	3.9 bleeds per year Interval 1.05 to 10.13
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants Treated Spontaneous Bleeds	1.2 bleeds per year Interval 0.06 to 5.99	0.2 bleeds per year Interval 0.0 to 4.01	2.2 bleeds per year Interval 0.32 to 7.59	0.9 bleeds per year Interval 0.01 to 5.33	1.5 bleeds per year Interval 0.1 to 6.35
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants Treated Joint Bleeds	0.9 bleeds per year Interval 0.02 to 5.42	0.1 bleeds per year Interval 0.0 to 3.95	0.4 bleeds per year Interval 0.0 to 4.53	0.4 bleeds per year Interval 0.0 to 4.56	0.5 bleeds per year Interval 0.0 to 4.73
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants Treated Target Joint Bleeds	0.4 bleeds per year Interval 0.0 to 4.44	0.1 bleeds per year Interval 0.0 to 3.79	0.3 bleeds per year Interval 0.0 to 4.35	0.4 bleeds per year Interval 0.0 to 4.4	0.3 bleeds per year Interval 0.0 to 4.3

SECONDARY outcome

Timeframe: From start of emicizumab treatment to study completion (median [min-max] efficacy observation period for all participants: 109.29 [0.1-249.1] weeks)

Population: All enrolled participants; for Arm B, it only includes participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis.

The number of bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (>/=) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration were excluded.

Outcome measures

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=35 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis n=18 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Emi): 1.5 mg/kg Emicizumab QW n=49 Participants This arm includes Arm B participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. After Week 24, emicizumab was administered at a loading dose of 3 mg/kg once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study.	Arm C: 1.5 mg/kg Emicizumab QW n=11 Participants Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	All Participants: 1.5 mg/kg Emicizumab QW n=113 Participants This analysis set included all enrolled participants on the study. For Arm B, it only all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Participants continued to receive bypassing agent therapy to treat breakthrough bleeds, with rFVIIa and/or aPCC.
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants Treated Target Joint Bleeds	0.0 bleeds per year Interval 0.0 to 0.0	0.0 bleeds per year Interval 0.0 to 0.0	0.0 bleeds per year Interval 0.0 to 0.0	0.0 bleeds per year Interval 0.0 to 0.0	0.0 bleeds per year Interval 0.0 to 0.0
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants Treated Bleeds	0.3 bleeds per year Interval 0.0 to 2.05	0.0 bleeds per year Interval 0.0 to 0.48	0.0 bleeds per year Interval 0.0 to 1.13	0.0 bleeds per year Interval 0.0 to 0.67	0.0 bleeds per year Interval 0.0 to 1.09
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants All Bleeds	1.9 bleeds per year Interval 0.22 to 5.13	0.5 bleeds per year Interval 0.0 to 2.18	0.6 bleeds per year Interval 0.0 to 2.25	0.5 bleeds per year Interval 0.0 to 4.41	0.6 bleeds per year Interval 0.0 to 3.34
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants Treated Spontaneous Bleeds	0.0 bleeds per year Interval 0.0 to 0.87	0.0 bleeds per year Interval 0.0 to 0.24	0.0 bleeds per year Interval 0.0 to 0.47	0.0 bleeds per year Interval 0.0 to 0.0	0.0 bleeds per year Interval 0.0 to 0.51
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Enrolled Participants Treated Joint Bleeds	0.0 bleeds per year Interval 0.0 to 0.24	0.0 bleeds per year Interval 0.0 to 0.0	0.0 bleeds per year Interval 0.0 to 0.0	0.0 bleeds per year Interval 0.0 to 0.0	0.0 bleeds per year Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, and 229-240 weeks

Population: All enrolled participants; for Arm B, it only includes participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. The number analyzed includes participants with available data over each interval.

The number of treated bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose.

Outcome measures

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=113 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Emi): 1.5 mg/kg Emicizumab QW This arm includes Arm B participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. After Week 24, emicizumab was administered at a loading dose of 3 mg/kg once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study.	Arm C: 1.5 mg/kg Emicizumab QW Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	All Participants: 1.5 mg/kg Emicizumab QW This analysis set included all enrolled participants on the study. For Arm B, it only all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Participants continued to receive bypassing agent therapy to treat breakthrough bleeds, with rFVIIa and/or aPCC.
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 133 to 144 Weeks	0.5 treated bleeds per year Interval 0.0 to 4.62	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 1 to 12 Weeks	3.9 treated bleeds per year Interval 1.05 to 10.12	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 13 to 24 Weeks	2.2 treated bleeds per year Interval 0.31 to 7.53	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 25 to 36 Weeks	0.9 treated bleeds per year Interval 0.01 to 5.31	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 37 to 48 Weeks	0.3 treated bleeds per year Interval 0.0 to 4.38	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 49 to 60 Weeks	0.4 treated bleeds per year Interval 0.0 to 4.56	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 61 to 72 Weeks	0.5 treated bleeds per year Interval 0.0 to 4.73	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 73 to 84 Weeks	0.6 treated bleeds per year Interval 0.0 to 4.8	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 85 to 96 Weeks	0.4 treated bleeds per year Interval 0.0 to 4.46	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 97 to 108 Weeks	0.5 treated bleeds per year Interval 0.0 to 4.71	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 109 to 120 Weeks	0.0 treated bleeds per year Interval to 3.69 The lower limit of the 95% confidence interval could not be calculated because too few events had occurred.	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 121 to 132 Weeks	0.4 treated bleeds per year Interval 0.0 to 4.48	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 145 to 156 Weeks	0.4 treated bleeds per year Interval 0.0 to 4.53	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 157 to 168 Weeks	0.2 treated bleeds per year Interval 0.0 to 4.01	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 169 to 180 Weeks	0.2 treated bleeds per year Interval 0.0 to 4.08	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 181 to 192 Weeks	0.0 treated bleeds per year Interval to 3.69 The lower limit of the 95% confidence interval could not be calculated because too few events had occurred.	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 193 to 204 Weeks	0.0 treated bleeds per year Interval to 3.69 The lower limit of the 95% confidence interval could not be calculated because too few events had occurred.	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 205 to 216 Weeks	0.0 treated bleeds per year Interval to 3.69 The lower limit of the 95% confidence interval could not be calculated because too few events had occurred.	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 217 to 228 Weeks	0.0 treated bleeds per year Interval to 3.69 The lower limit of the 95% confidence interval could not be calculated because too few events had occurred.	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 229 to 240 Weeks	0.0 treated bleeds per year Interval to 3.69 The lower limit of the 95% confidence interval could not be calculated because too few events had occurred.	—	—	—	—

SECONDARY outcome

Timeframe: 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, and 229-240 weeks

Population: All enrolled participants; for Arm B, it only includes participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. The number analyzed includes participants with available data over each interval.

The number of treated bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose.

Outcome measures

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=113 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Emi): 1.5 mg/kg Emicizumab QW This arm includes Arm B participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. After Week 24, emicizumab was administered at a loading dose of 3 mg/kg once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study.	Arm C: 1.5 mg/kg Emicizumab QW Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	All Participants: 1.5 mg/kg Emicizumab QW This analysis set included all enrolled participants on the study. For Arm B, it only all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Participants continued to receive bypassing agent therapy to treat breakthrough bleeds, with rFVIIa and/or aPCC.
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 1 to 12 Weeks	0.0 treated bleeds per year Interval 0.0 to 4.35	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 13 to 24 Weeks	0.0 treated bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 25 to 36 Weeks	0.0 treated bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 37 to 48 Weeks	0.0 treated bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 49 to 60 Weeks	0.0 treated bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 61 to 72 Weeks	0.0 treated bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 73 to 84 Weeks	0.0 treated bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 85 to 96 Weeks	0.0 treated bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 97 to 108 Weeks	0.0 treated bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 109 to 120 Weeks	0.0 treated bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 121 to 132 Weeks	0.0 treated bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 133 to 144 Weeks	0.0 treated bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 145 to 156 Weeks	0.0 treated bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 157 to 168 Weeks	0.0 treated bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 169 to 180 Weeks	0.0 treated bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 181 to 192 Weeks	0.0 treated bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 193 to 204 Weeks	0.0 treated bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 205 to 216 Weeks	0.0 treated bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 217 to 228 Weeks	0.0 treated bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 229 to 240 Weeks	0.0 treated bleeds per year Interval 0.0 to 0.0	—	—	—	—

SECONDARY outcome

Timeframe: 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, and 229-240 weeks

Population: All enrolled participants; for Arm B, it only includes participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. The number analyzed includes participants with available data over each interval.

The number of all bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. All bleeds included both treated bleeds (with coagulation factors) and non-treated bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose.

Outcome measures

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=113 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Emi): 1.5 mg/kg Emicizumab QW This arm includes Arm B participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. After Week 24, emicizumab was administered at a loading dose of 3 mg/kg once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study.	Arm C: 1.5 mg/kg Emicizumab QW Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	All Participants: 1.5 mg/kg Emicizumab QW This analysis set included all enrolled participants on the study. For Arm B, it only all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Participants continued to receive bypassing agent therapy to treat breakthrough bleeds, with rFVIIa and/or aPCC.
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 1 to 12 Weeks	6.2 all bleeds per year Interval 2.35 to 13.4	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 13 to 24 Weeks	3.4 all bleeds per year Interval 0.78 to 9.29	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 25 to 36 Weeks	1.5 all bleeds per year Interval 0.11 to 6.4	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 37 to 48 Weeks	1.4 all bleeds per year Interval 0.09 to 6.29	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 49 to 60 Weeks	1.1 all bleeds per year Interval 0.04 to 5.74	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 61 to 72 Weeks	1.0 all bleeds per year Interval 0.02 to 5.53	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 73 to 84 Weeks	1.3 all bleeds per year Interval 0.07 to 6.12	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 85 to 96 Weeks	1.0 all bleeds per year Interval 0.02 to 5.56	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 97 to 108 Weeks	1.2 all bleeds per year Interval 0.05 to 5.86	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 109 to 120 Weeks	0.9 all bleeds per year Interval 0.01 to 5.34	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 121 to 132 Weeks	0.8 all bleeds per year Interval 0.01 to 5.2	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 133 to 144 Weeks	0.5 all bleeds per year Interval 0.0 to 4.62	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 145 to 156 Weeks	0.8 all bleeds per year Interval 0.01 to 5.29	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 157 to 168 Weeks	0.3 all bleeds per year Interval 0.0 to 4.31	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 169 to 180 Weeks	0.8 all bleeds per year Interval 0.01 to 5.14	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 181 to 192 Weeks	0.2 all bleeds per year Interval 0.0 to 4.15	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 193 to 204 Weeks	0.0 all bleeds per year Interval to 3.69 The lower limit of the 95% confidence interval could not be calculated because too few events had occurred.	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 205 to 216 Weeks	0.0 all bleeds per year Interval to 3.69 The lower limit of the 95% confidence interval could not be calculated because too few events had occurred.	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 217 to 228 Weeks	0.0 all bleeds per year Interval to 3.69 The lower limit of the 95% confidence interval could not be calculated because too few events had occurred.	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 229 to 240 Weeks	0.0 all bleeds per year Interval to 3.69 The lower limit of the 95% confidence interval could not be calculated because too few events had occurred.	—	—	—	—

SECONDARY outcome

Timeframe: 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, and 229-240 weeks

Population: All enrolled participants; for Arm B, it only includes participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. The number analyzed includes participants with available data over each interval.

The number of all bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. All bleeds included both treated bleeds (with coagulation factors) and non-treated bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose.

Outcome measures

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=113 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Emi): 1.5 mg/kg Emicizumab QW This arm includes Arm B participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. After Week 24, emicizumab was administered at a loading dose of 3 mg/kg once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study.	Arm C: 1.5 mg/kg Emicizumab QW Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	All Participants: 1.5 mg/kg Emicizumab QW This analysis set included all enrolled participants on the study. For Arm B, it only all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Participants continued to receive bypassing agent therapy to treat breakthrough bleeds, with rFVIIa and/or aPCC.
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 1 to 12 Weeks	0.0 all bleeds per year Interval 0.0 to 8.7	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 13 to 24 Weeks	0.0 all bleeds per year Interval 0.0 to 4.35	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 25 to 36 Weeks	0.0 all bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 37 to 48 Weeks	0.0 all bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 49 to 60 Weeks	0.0 all bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 61 to 72 Weeks	0.0 all bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 73 to 84 Weeks	0.0 all bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 85 to 96 Weeks	0.0 all bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 97 to 108 Weeks	0.0 all bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 109 to 120 Weeks	0.0 all bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 121 to 132 Weeks	0.0 all bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 133 to 144 Weeks	0.0 all bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 145 to 156 Weeks	0.0 all bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 157 to 168 Weeks	0.0 all bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 169 to 180 Weeks	0.0 all bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 181 to 192 Weeks	0.0 all bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 193 to 204 Weeks	0.0 all bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 205 to 216 Weeks	0.0 all bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 217 to 228 Weeks	0.0 all bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 229 to 240 Weeks	0.0 all bleeds per year Interval 0.0 to 0.0	—	—	—	—

SECONDARY outcome

Timeframe: 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, and 229-240 weeks

Population: All enrolled participants; for Arm B, it only includes participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. The number analyzed includes participants with available data over each interval.

The number of treated spontaneous bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated spontaneous bleeds were defined as treated (with coagulation factors) bleeds with no known contributing factor (e.g., trauma, surgery). The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose.

Outcome measures

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=113 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Emi): 1.5 mg/kg Emicizumab QW This arm includes Arm B participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. After Week 24, emicizumab was administered at a loading dose of 3 mg/kg once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study.	Arm C: 1.5 mg/kg Emicizumab QW Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	All Participants: 1.5 mg/kg Emicizumab QW This analysis set included all enrolled participants on the study. For Arm B, it only all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Participants continued to receive bypassing agent therapy to treat breakthrough bleeds, with rFVIIa and/or aPCC.
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 169 to 180 Weeks	0.2 treated spontaneous bleeds per year Interval 0.0 to 4.08	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 181 to 192 Weeks	0.0 treated spontaneous bleeds per year Interval to 3.69 The lower limit of the 95% confidence interval could not be calculated because too few events had occurred.	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 1 to 12 Weeks	2.2 treated spontaneous bleeds per year Interval 0.31 to 7.56	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 13 to 24 Weeks	1.3 treated spontaneous bleeds per year Interval 0.06 to 6.04	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 25 to 36 Weeks	0.4 treated spontaneous bleeds per year Interval 0.0 to 4.45	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 37 to 48 Weeks	0.2 treated spontaneous bleeds per year Interval 0.0 to 4.04	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 49 to 60 Weeks	0.1 treated spontaneous bleeds per year Interval 0.0 to 3.96	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 61 to 72 Weeks	0.2 treated spontaneous bleeds per year Interval 0.0 to 4.05	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 73 to 84 Weeks	0.2 treated spontaneous bleeds per year Interval 0.0 to 4.08	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 85 to 96 Weeks	0.1 treated spontaneous bleeds per year Interval 0.0 to 3.92	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 97 to 108 Weeks	0.3 treated spontaneous bleeds per year Interval 0.0 to 4.34	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 109 to 120 Weeks	0.0 treated spontaneous bleeds per year Interval to 3.69 The lower limit of the 95% confidence interval could not be calculated because too few events had occurred.	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 121 to 132 Weeks	0.1 treated spontaneous bleeds per year Interval 0.0 to 3.89	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 133 to 144 Weeks	0.0 treated spontaneous bleeds per year Interval to 3.69 The lower limit of the 95% confidence interval could not be calculated because too few events had occurred.	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 145 to 156 Weeks	0.4 treated spontaneous bleeds per year Interval 0.0 to 4.53	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 157 to 168 Weeks	0.2 treated spontaneous bleeds per year Interval 0.0 to 4.01	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 193 to 204 Weeks	0.0 treated spontaneous bleeds per year Interval to 3.69 The lower limit of the 95% confidence interval could not be calculated because too few events had occurred.	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 205 to 216 Weeks	0.0 treated spontaneous bleeds per year Interval to 3.69 The lower limit of the 95% confidence interval could not be calculated because too few events had occurred.	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 217 to 228 Weeks	0.0 treated spontaneous bleeds per year Interval to 3.69 The lower limit of the 95% confidence interval could not be calculated because too few events had occurred.	—	—	—	—
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 229 to 240 Weeks	0.0 treated spontaneous bleeds per year Interval to 3.69 The lower limit of the 95% confidence interval could not be calculated because too few events had occurred.	—	—	—	—

SECONDARY outcome

Timeframe: 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, and 229-240 weeks

Population: All enrolled participants; for Arm B, it only includes participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. The number analyzed includes participants with available data over each interval.

The number of treated spontaneous bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated spontaneous bleeds were defined as treated (with coagulation factors) bleeds with no known contributing factor (e.g., trauma, surgery). The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants whose dose was up-titrated, the efficacy period ended the day before the first day on the up-titrated dose.

Outcome measures

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=113 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Emi): 1.5 mg/kg Emicizumab QW This arm includes Arm B participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. After Week 24, emicizumab was administered at a loading dose of 3 mg/kg once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study.	Arm C: 1.5 mg/kg Emicizumab QW Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	All Participants: 1.5 mg/kg Emicizumab QW This analysis set included all enrolled participants on the study. For Arm B, it only all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Participants continued to receive bypassing agent therapy to treat breakthrough bleeds, with rFVIIa and/or aPCC.
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 1 to 12 Weeks	0.0 treated spontaneous bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 13 to 24 Weeks	0.0 treated spontaneous bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 25 to 36 Weeks	0.0 treated spontaneous bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 37 to 48 Weeks	0.0 treated spontaneous bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 49 to 60 Weeks	0.0 treated spontaneous bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 61 to 72 Weeks	0.0 treated spontaneous bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 73 to 84 Weeks	0.0 treated spontaneous bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 85 to 96 Weeks	0.0 treated spontaneous bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 97 to 108 Weeks	0.0 treated spontaneous bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 109 to 120 Weeks	0.0 treated spontaneous bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 121 to 132 Weeks	0.0 treated spontaneous bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 133 to 144 Weeks	0.0 treated spontaneous bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 145 to 156 Weeks	0.0 treated spontaneous bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 157 to 168 Weeks	0.0 treated spontaneous bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 169 to 180 Weeks	0.0 treated spontaneous bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 181 to 192 Weeks	0.0 treated spontaneous bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 193 to 204 Weeks	0.0 treated spontaneous bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 205 to 216 Weeks	0.0 treated spontaneous bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 217 to 228 Weeks	0.0 treated spontaneous bleeds per year Interval 0.0 to 0.0	—	—	—	—
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Enrolled Participants 229 to 240 Weeks	0.0 treated spontaneous bleeds per year Interval 0.0 to 0.0	—	—	—	—

SECONDARY outcome

Timeframe: From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks)

Population: Safety Population: All treated participants grouped by their assigned treatment. For Arm B, data collected while receiving episodic bypassing agents (no prophyalxis) for the first 24 weeks and 1.5 mg/kg emicizumab QW after Week 24 are reported separately under 'Arm B (Control): No Prophylaxis' and 'Arm B (Emi): 1.5 mg/kg Emicizumab QW', respectively.

Investigators sought information on adverse events (AEs) at each contact with participants. The WHO toxicity grading scale was used for assessing AE severity (i.e., intensity of an AE); any AEs not specifically listed in the WHO toxicity grading scale were assessed for severity according to the following grades: Grade 1 is mild; Grade 2 is moderate, Grade 3 is severe; Grade 4 is life-threatening; and Grade 5 is death. Regardless of severity, some AEs may have also met seriousness criteria. The terms "severe" and "serious" are not synonymous; severity and seriousness were independently assessed for each AE. For participants whose emicizumab dose was up-titrated, only data before up-titration is included. aPCC = activated prothrombin complex concentrate; Hypersens.= hypersensitivity

Outcome measures

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=34 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis n=18 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Emi): 1.5 mg/kg Emicizumab QW n=18 Participants This arm includes Arm B participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. After Week 24, emicizumab was administered at a loading dose of 3 mg/kg once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study.	Arm C: 1.5 mg/kg Emicizumab QW n=49 Participants Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	All Participants: 1.5 mg/kg Emicizumab QW n=11 Participants This analysis set included all enrolled participants on the study. For Arm B, it only all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Participants continued to receive bypassing agent therapy to treat breakthrough bleeds, with rFVIIa and/or aPCC.
Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale Any Adverse Event (AE)	34 Participants	9 Participants	15 Participants	46 Participants	9 Participants
Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale AE with Fatal Outcome	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale Serious AE	10 Participants	4 Participants	4 Participants	9 Participants	2 Participants
Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale AE Leading to Withdrawal from Treatment	2 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale AE Leading to Dose Mod./Interruption	1 Participants	0 Participants	0 Participants	5 Participants	0 Participants
Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale Grade ≥3 AE	10 Participants	4 Participants	3 Participants	7 Participants	3 Participants
Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale Related AE	15 Participants	0 Participants	4 Participants	13 Participants	4 Participants
Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale Local Injection Site Reaction	9 Participants	0 Participants	3 Participants	7 Participants	4 Participants
Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale Systemic Hypersens./Anaphylac(tic/toid) Reaction	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale Thrombotic Microangiopathy (TMA)	1 Participants	0 Participants	0 Participants	2 Participants	0 Participants
Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale TMA Event Related to aPCC and Emicizumab	1 Participants	0 Participants	0 Participants	2 Participants	0 Participants
Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale Thromboembolic Event (TE)	1 Participants	1 Participants	1 Participants	1 Participants	0 Participants
Safety Summary of the Overall Number and Percentage of Participants With at Least One Adverse Event, Severity Assessed According to the WHO Toxicity Grading Scale TE Event Related to aPCC and Emicizumab	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks)

Population: All emicizumab-treated participants included Arms A, C, and D and Arm B participants who switched to receive emicizumab (Arm B Emi). The overall number of participants analyzed is the number of participants with at least one post-baseline anti-drug antibody assessment.

'Total ADA Negative' is the sum of all subjects who tested negative for ADA in the 2 following categories: 'ADA Negative', those who are pre-dose ADA negative or are missing pre-dose ADA data and who have all negative post-dose ADA results; and 'ADA Negative (Treatment Unaffected)', a subset who are pre-dose ADA positive but do not have a ≥4-fold increase in post-dose ADA levels compared to baseline measurement. 'Total ADA Positive' is the sum of all subjects who tested positive for ADA in the 2 following categories: 'ADA Positive (Treatment Boosted)', those who are pre-dose ADA positive and have a ≥4-fold increase in post-dose ADA levels compared to baseline measurement; and 'ADA Positive (Treatment Induced)', those who are pre-dose ADA negative or missing data and who have at least one post-dose ADA positive sample. ADA-positive samples were further analyzed for neutralizing capacity using a modified FVIII chromogenic assay; if also positive, they were considered neutralizing ADAs.

Outcome measures

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=33 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis n=18 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Emi): 1.5 mg/kg Emicizumab QW n=49 Participants This arm includes Arm B participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. After Week 24, emicizumab was administered at a loading dose of 3 mg/kg once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study.	Arm C: 1.5 mg/kg Emicizumab QW n=11 Participants Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	All Participants: 1.5 mg/kg Emicizumab QW This analysis set included all enrolled participants on the study. For Arm B, it only all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Participants continued to receive bypassing agent therapy to treat breakthrough bleeds, with rFVIIa and/or aPCC.
Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study Total ADA Negative (Neg+Neg Unaffected)	33 Participants	18 Participants	47 Participants	11 Participants	—
Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study ADA Negative, Negative	33 Participants	17 Participants	46 Participants	11 Participants	—
Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study ADA Negative, Negative (Treatment Unaffected)	0 Participants	1 Participants	1 Participants	0 Participants	—
Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study Total ADA Positive (Boosted + Induced)	0 Participants	0 Participants	2 Participants	0 Participants	—
Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study ADA Positive, Positive (Treatment Boosted)	0 Participants	0 Participants	0 Participants	0 Participants	—
Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study ADA Positive, Positive (Treatment Induced)	0 Participants	0 Participants	2 Participants	0 Participants	—
Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study ADA Positive with Neutralizing ADAs	0 Participants	0 Participants	2 Participants	0 Participants	—

SECONDARY outcome

Timeframe: Pre-dose (0 hour [hr]) on Weeks 1-5, 7, 9, 13, 17, 21, 25, 33, 41, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, and 169 (For Arm B (Emi), Study Weeks are relative to first emicizumab dose)

Population: Pharmacokinetic (PK) evaluable population included all participants who received at least one dose of emicizumab and had at least one post-dose emicizumab concentration result. The number analyzed includes participants with PK samples at each timepoint.

Plasma concentrations of emicizumab were analyzed using a validated Enzyme Linked Immunosorbent Assay (ELISA). The lower limit of quantification (LLOQ) was 100 nanograms per milliliter (ng/mL). Because participants in Arm B switched from episodic bypassing agents to start receiving emicizumab prophylaxis after Week 24, the timepoints for Arm B (Emi) are expressed relative to first emicizumab dose.

Outcome measures

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=34 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis n=18 Participants Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Emi): 1.5 mg/kg Emicizumab QW n=49 Participants This arm includes Arm B participants who switched to emicizumab prophylaxis after having completed the first 24 weeks on study with no prophylaxis. After Week 24, emicizumab was administered at a loading dose of 3 mg/kg once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study.	Arm C: 1.5 mg/kg Emicizumab QW n=11 Participants Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	All Participants: 1.5 mg/kg Emicizumab QW n=112 Participants This analysis set included all enrolled participants on the study. For Arm B, it only all participants starting after Week 24 on study when they crossed over to first receive prophylactic treatment with emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Participants continued to receive bypassing agent therapy to treat breakthrough bleeds, with rFVIIa and/or aPCC.
Plasma Trough Concentrations of Emicizumab at Specified Timepoints Week 3	31.6 micrograms per milliliter (mcg/mL) Standard Deviation 7.3	32.3 micrograms per milliliter (mcg/mL) Standard Deviation 10.4	31.7 micrograms per milliliter (mcg/mL) Standard Deviation 8.3	32.7 micrograms per milliliter (mcg/mL) Standard Deviation 13.0	31.9 micrograms per milliliter (mcg/mL) Standard Deviation 8.8
Plasma Trough Concentrations of Emicizumab at Specified Timepoints Week 85	56.9 micrograms per milliliter (mcg/mL) Standard Deviation 18.3	42.5 micrograms per milliliter (mcg/mL) Standard Deviation 34.4	56.6 micrograms per milliliter (mcg/mL) Standard Deviation 22.7	50.9 micrograms per milliliter (mcg/mL) Standard Deviation 12.5	54.5 micrograms per milliliter (mcg/mL) Standard Deviation 22.7
Plasma Trough Concentrations of Emicizumab at Specified Timepoints Week 1	NA micrograms per milliliter (mcg/mL) Standard Deviation NA No data available because all of the measurements were below the LLOQ.	NA micrograms per milliliter (mcg/mL) Standard Deviation NA No data available because all of the measurements were below the LLOQ.	NA micrograms per milliliter (mcg/mL) Standard Deviation NA No data available because all of the measurements were below the LLOQ.	NA micrograms per milliliter (mcg/mL) Standard Deviation NA No data available because all of the measurements were below the LLOQ.	NA micrograms per milliliter (mcg/mL) Standard Deviation NA No data available because all of the measurements were below the LLOQ.
Plasma Trough Concentrations of Emicizumab at Specified Timepoints Week 2	16.2 micrograms per milliliter (mcg/mL) Standard Deviation 4.4	21.7 micrograms per milliliter (mcg/mL) Standard Deviation 10.6	15.8 micrograms per milliliter (mcg/mL) Standard Deviation 5.5	18.3 micrograms per milliliter (mcg/mL) Standard Deviation 6.5	17.1 micrograms per milliliter (mcg/mL) Standard Deviation 6.6
Plasma Trough Concentrations of Emicizumab at Specified Timepoints Week 4	43.8 micrograms per milliliter (mcg/mL) Standard Deviation 12.2	44.6 micrograms per milliliter (mcg/mL) Standard Deviation 18.6	44.7 micrograms per milliliter (mcg/mL) Standard Deviation 11.5	49.0 micrograms per milliliter (mcg/mL) Standard Deviation 13.5	44.9 micrograms per milliliter (mcg/mL) Standard Deviation 13.2
Plasma Trough Concentrations of Emicizumab at Specified Timepoints Week 5	53.5 micrograms per milliliter (mcg/mL) Standard Deviation 15.1	52.2 micrograms per milliliter (mcg/mL) Standard Deviation 14.2	54.0 micrograms per milliliter (mcg/mL) Standard Deviation 13.2	59.1 micrograms per milliliter (mcg/mL) Standard Deviation 14.6	54.1 micrograms per milliliter (mcg/mL) Standard Deviation 14.0
Plasma Trough Concentrations of Emicizumab at Specified Timepoints Week 7	52.8 micrograms per milliliter (mcg/mL) Standard Deviation 16.2	53.3 micrograms per milliliter (mcg/mL) Standard Deviation 18.0	53.6 micrograms per milliliter (mcg/mL) Standard Deviation 14.3	54.9 micrograms per milliliter (mcg/mL) Standard Deviation 9.2	53.4 micrograms per milliliter (mcg/mL) Standard Deviation 14.9
Plasma Trough Concentrations of Emicizumab at Specified Timepoints Week 9	50.4 micrograms per milliliter (mcg/mL) Standard Deviation 12.4	48.9 micrograms per milliliter (mcg/mL) Standard Deviation 16.7	52.6 micrograms per milliliter (mcg/mL) Standard Deviation 15.7	53.7 micrograms per milliliter (mcg/mL) Standard Deviation 13.8	51.5 micrograms per milliliter (mcg/mL) Standard Deviation 14.7
Plasma Trough Concentrations of Emicizumab at Specified Timepoints Week 13	49.3 micrograms per milliliter (mcg/mL) Standard Deviation 13.4	45.2 micrograms per milliliter (mcg/mL) Standard Deviation 16.2	52.6 micrograms per milliliter (mcg/mL) Standard Deviation 15.0	53.4 micrograms per milliliter (mcg/mL) Standard Deviation 14.0	50.5 micrograms per milliliter (mcg/mL) Standard Deviation 14.7
Plasma Trough Concentrations of Emicizumab at Specified Timepoints Week 17	50.7 micrograms per milliliter (mcg/mL) Standard Deviation 15.0	46.5 micrograms per milliliter (mcg/mL) Standard Deviation 17.4	51.2 micrograms per milliliter (mcg/mL) Standard Deviation 14.9	57.5 micrograms per milliliter (mcg/mL) Standard Deviation 16.9	51.0 micrograms per milliliter (mcg/mL) Standard Deviation 15.6
Plasma Trough Concentrations of Emicizumab at Specified Timepoints Week 21	52.6 micrograms per milliliter (mcg/mL) Standard Deviation 17.4	44.5 micrograms per milliliter (mcg/mL) Standard Deviation 15.4	51.6 micrograms per milliliter (mcg/mL) Standard Deviation 17.1	55.0 micrograms per milliliter (mcg/mL) Standard Deviation 13.7	51.1 micrograms per milliliter (mcg/mL) Standard Deviation 16.6
Plasma Trough Concentrations of Emicizumab at Specified Timepoints Week 25	54.6 micrograms per milliliter (mcg/mL) Standard Deviation 19.1	45.8 micrograms per milliliter (mcg/mL) Standard Deviation 18.6	50.4 micrograms per milliliter (mcg/mL) Standard Deviation 16.8	52.8 micrograms per milliliter (mcg/mL) Standard Deviation 14.1	51.2 micrograms per milliliter (mcg/mL) Standard Deviation 17.6
Plasma Trough Concentrations of Emicizumab at Specified Timepoints Week 33	50.7 micrograms per milliliter (mcg/mL) Standard Deviation 17.2	48.1 micrograms per milliliter (mcg/mL) Standard Deviation 21.1	54.8 micrograms per milliliter (mcg/mL) Standard Deviation 16.7	57.1 micrograms per milliliter (mcg/mL) Standard Deviation 15.2	52.7 micrograms per milliliter (mcg/mL) Standard Deviation 17.5
Plasma Trough Concentrations of Emicizumab at Specified Timepoints Week 41	45.3 micrograms per milliliter (mcg/mL) Standard Deviation 13.7	49.3 micrograms per milliliter (mcg/mL) Standard Deviation 25.9	54.8 micrograms per milliliter (mcg/mL) Standard Deviation 23.4	63.3 micrograms per milliliter (mcg/mL) Standard Deviation 19.4	52.0 micrograms per milliliter (mcg/mL) Standard Deviation 21.6
Plasma Trough Concentrations of Emicizumab at Specified Timepoints Week 49	48.0 micrograms per milliliter (mcg/mL) Standard Deviation 12.3	54.6 micrograms per milliliter (mcg/mL) Standard Deviation 27.6	56.1 micrograms per milliliter (mcg/mL) Standard Deviation 22.2	55.1 micrograms per milliliter (mcg/mL) Standard Deviation 18.7	53.3 micrograms per milliliter (mcg/mL) Standard Deviation 20.5
Plasma Trough Concentrations of Emicizumab at Specified Timepoints Week 61	52.2 micrograms per milliliter (mcg/mL) Standard Deviation 16.3	51.8 micrograms per milliliter (mcg/mL) Standard Deviation 33.4	60.9 micrograms per milliliter (mcg/mL) Standard Deviation 27.7	53.2 micrograms per milliliter (mcg/mL) Standard Deviation 13.8	56.0 micrograms per milliliter (mcg/mL) Standard Deviation 24.8
Plasma Trough Concentrations of Emicizumab at Specified Timepoints Week 73	55.5 micrograms per milliliter (mcg/mL) Standard Deviation 14.9	45.6 micrograms per milliliter (mcg/mL) Standard Deviation 26.2	62.9 micrograms per milliliter (mcg/mL) Standard Deviation 24.9	51.9 micrograms per milliliter (mcg/mL) Standard Deviation 13.0	57.1 micrograms per milliliter (mcg/mL) Standard Deviation 22.0
Plasma Trough Concentrations of Emicizumab at Specified Timepoints Week 97	53.2 micrograms per milliliter (mcg/mL) Standard Deviation 15.2	34.4 micrograms per milliliter (mcg/mL) Standard Deviation 26.4	54.6 micrograms per milliliter (mcg/mL) Standard Deviation 20.0	53.8 micrograms per milliliter (mcg/mL) Standard Deviation 16.9	51.3 micrograms per milliliter (mcg/mL) Standard Deviation 19.9
Plasma Trough Concentrations of Emicizumab at Specified Timepoints Week 109	49.6 micrograms per milliliter (mcg/mL) Standard Deviation 15.9	32.8 micrograms per milliliter (mcg/mL) Standard Deviation 31.4	47.4 micrograms per milliliter (mcg/mL) Standard Deviation 12.4	49.3 micrograms per milliliter (mcg/mL) Standard Deviation 12.8	46.7 micrograms per milliliter (mcg/mL) Standard Deviation 17.6
Plasma Trough Concentrations of Emicizumab at Specified Timepoints Week 121	53.8 micrograms per milliliter (mcg/mL) Standard Deviation 16.3	36.1 micrograms per milliliter (mcg/mL) Standard Deviation 33.6	46.3 micrograms per milliliter (mcg/mL) Standard Deviation 12.5	53.1 micrograms per milliliter (mcg/mL) Standard Deviation 5.0	48.5 micrograms per milliliter (mcg/mL) Standard Deviation 19.7
Plasma Trough Concentrations of Emicizumab at Specified Timepoints Week 133	50.5 micrograms per milliliter (mcg/mL) Standard Deviation 15.9	48.7 micrograms per milliliter (mcg/mL) Standard Deviation 29.4	49.0 micrograms per milliliter (mcg/mL) Standard Deviation 18.5	52.0 micrograms per milliliter (mcg/mL) Standard Deviation NA Standard deviation (SD) could not be calculated for single participant data.	49.8 micrograms per milliliter (mcg/mL) Standard Deviation 18.8
Plasma Trough Concentrations of Emicizumab at Specified Timepoints Week 145	51.3 micrograms per milliliter (mcg/mL) Standard Deviation 16.6	38.2 micrograms per milliliter (mcg/mL) Standard Deviation 19.0	44.0 micrograms per milliliter (mcg/mL) Standard Deviation 21.7	49.5 micrograms per milliliter (mcg/mL) Standard Deviation 10.3	47.4 micrograms per milliliter (mcg/mL) Standard Deviation 17.4
Plasma Trough Concentrations of Emicizumab at Specified Timepoints Week 157	58.0 micrograms per milliliter (mcg/mL) Standard Deviation 16.5	—	45.5 micrograms per milliliter (mcg/mL) Standard Deviation 17.0	55.4 micrograms per milliliter (mcg/mL) Standard Deviation 19.2	55.3 micrograms per milliliter (mcg/mL) Standard Deviation 16.7
Plasma Trough Concentrations of Emicizumab at Specified Timepoints Week 169	55.0 micrograms per milliliter (mcg/mL) Standard Deviation 19.3	—	43.2 micrograms per milliliter (mcg/mL) Standard Deviation 20.2	50.8 micrograms per milliliter (mcg/mL) Standard Deviation NA Standard deviation (SD) could not be calculated for single participant data.	52.5 micrograms per milliliter (mcg/mL) Standard Deviation 18.7

Adverse Events

Arm A: 1.5 mg/kg Emicizumab QW

Serious events: 11 serious events

Other events: 33 other events

Deaths: 0 deaths

Arm B (Control): No Prophylaxis

Serious events: 5 serious events

Other events: 9 other events

Deaths: 0 deaths

Arm B (Emi): 1.5 mg/kg Emicizumab QW

Serious events: 4 serious events

Other events: 15 other events

Deaths: 0 deaths

Arm C: 1.5 mg/kg Emicizumab QW

Serious events: 9 serious events

Other events: 42 other events

Deaths: 1 deaths

Arm D: 1.5 mg/kg Emicizumab QW

Serious events: 2 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=34 participants at risk Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis n=18 participants at risk Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. The safety data reported here represents data collected from all Arm B participants during the first 24 weeks of 'no prophylaxis'; safety data from Arm B participants who switched to emicizumab after Week 24 are reported separately under Arm B (Emi): 1.5 mg/kg Emicizumab QW.	Arm B (Emi): 1.5 mg/kg Emicizumab QW n=18 participants at risk This arm includes Arm B participants who switched to emicizumab prophylaxis after completing at least 24-week no prophylaxis. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks (after at least 24 weeks) followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Data reported represents data collected during emicizumab treatment only.	Arm C: 1.5 mg/kg Emicizumab QW n=49 participants at risk Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm D: 1.5 mg/kg Emicizumab QW n=11 participants at risk Participants who were either: 1) Receiving episodic bypassing agents prior to study entry but were unable to enroll in Arms A or B; or 2) Receiving bypassing agent prophylaxis prior to study entry but were unable to enroll in Arm C, were enrolled in Arm D to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.
Infections and infestations Meningitis bacterial	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Infections and infestations Vascular device infection	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Blood and lymphatic system disorders Iron deficiency anaemia	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Blood and lymphatic system disorders Thrombotic microangiopathy	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	4.1% 2/49 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Musculoskeletal and connective tissue disorders Muscle haemorrhage	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Skin and subcutaneous tissue disorders Skin necrosis	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Vascular disorders Thrombophlebitis superficial	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Gastrointestinal disorders Gastrointestinal haemorrhage	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Infections and infestations Device related infection	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Infections and infestations Urinary tract infection	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Musculoskeletal and connective tissue disorders Haemarthrosis	5.9% 2/34 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	11.1% 2/18 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	4.1% 2/49 • Number of events 3 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Infections and infestations Cavernous sinus thrombosis	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Infections and infestations Sepsis	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Nervous system disorders Headache	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Renal and urinary disorders Haematuria	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Musculoskeletal and connective tissue disorders Osteonecrosis	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Musculoskeletal and connective tissue disorders Soft tissue haemorrhage	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Vascular disorders Haematoma	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Vascular disorders Haemorrhage	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	4.1% 2/49 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Gastrointestinal disorders Large intestine polyp	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Gastrointestinal disorders Tooth development disorder	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	9.1% 1/11 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
General disorders Chest pain	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Infections and infestations Gastroenteritis viral	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Infections and infestations Device related sepsis	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Injury, poisoning and procedural complications Subdural haemorrhage	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Injury, poisoning and procedural complications Road traffic accident	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	9.1% 1/11 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Product Issues Device loosening	2.9% 1/34 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Psychiatric disorders Intentional self-injury	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Renal and urinary disorders Subcapsular renal haematoma	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Infections and infestations Gastroenteritis	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Psychiatric disorders Delirium	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.

Other adverse events

Measure	Arm A: 1.5 mg/kg Emicizumab QW n=34 participants at risk Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm B (Control): No Prophylaxis n=18 participants at risk Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. The safety data reported here represents data collected from all Arm B participants during the first 24 weeks of 'no prophylaxis'; safety data from Arm B participants who switched to emicizumab after Week 24 are reported separately under Arm B (Emi): 1.5 mg/kg Emicizumab QW.	Arm B (Emi): 1.5 mg/kg Emicizumab QW n=18 participants at risk This arm includes Arm B participants who switched to emicizumab prophylaxis after completing at least 24-week no prophylaxis. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks (after at least 24 weeks) followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. Data reported represents data collected during emicizumab treatment only.	Arm C: 1.5 mg/kg Emicizumab QW n=49 participants at risk Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.	Arm D: 1.5 mg/kg Emicizumab QW n=11 participants at risk Participants who were either: 1) Receiving episodic bypassing agents prior to study entry but were unable to enroll in Arms A or B; or 2) Receiving bypassing agent prophylaxis prior to study entry but were unable to enroll in Arm C, were enrolled in Arm D to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.
Ear and labyrinth disorders Ear discomfort	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Gastrointestinal disorders Abdominal pain upper	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	4.1% 2/49 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Gastrointestinal disorders Enteritis	5.9% 2/34 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Gastrointestinal disorders Large intestine polyp	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Gastrointestinal disorders Toothache	11.8% 4/34 • Number of events 4 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	11.1% 2/18 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	4.1% 2/49 • Number of events 3 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	18.2% 2/11 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
General disorders Chest pain	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
General disorders Fatigue	8.8% 3/34 • Number of events 4 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	11.1% 2/18 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	4.1% 2/49 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
General disorders Injection site reaction	26.5% 9/34 • Number of events 18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	16.7% 3/18 • Number of events 3 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	16.3% 8/49 • Number of events 21 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	36.4% 4/11 • Number of events 5 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
General disorders Pyrexia	5.9% 2/34 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	11.1% 2/18 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	16.3% 8/49 • Number of events 10 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	9.1% 1/11 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Infections and infestations Folliculitis	5.9% 2/34 • Number of events 3 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Infections and infestations Nasopharyngitis	32.4% 11/34 • Number of events 29 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	11.1% 2/18 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	38.9% 7/18 • Number of events 14 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	32.7% 16/49 • Number of events 27 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	18.2% 2/11 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Infections and infestations Upper respiratory tract infection	23.5% 8/34 • Number of events 21 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	11.1% 2/18 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	11.1% 2/18 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	14.3% 7/49 • Number of events 8 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	18.2% 2/11 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Injury, poisoning and procedural complications Post procedural constipation	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Injury, poisoning and procedural complications Procedural hypotension	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Injury, poisoning and procedural complications Procedural nausea	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Injury, poisoning and procedural complications Procedural pain	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	11.1% 2/18 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	4.1% 2/49 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Investigations Blood glucose increased	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Metabolism and nutrition disorders Dehydration	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Metabolism and nutrition disorders Electrolyte imbalance	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Musculoskeletal and connective tissue disorders Arthralgia	26.5% 9/34 • Number of events 17 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	33.3% 6/18 • Number of events 9 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	24.5% 12/49 • Number of events 33 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	27.3% 3/11 • Number of events 5 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Musculoskeletal and connective tissue disorders Myalgia	5.9% 2/34 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Nervous system disorders Headache	17.6% 6/34 • Number of events 9 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	22.2% 4/18 • Number of events 4 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	26.5% 13/49 • Number of events 22 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	27.3% 3/11 • Number of events 3 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Respiratory, thoracic and mediastinal disorders Cough	14.7% 5/34 • Number of events 5 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	6.1% 3/49 • Number of events 3 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	4.1% 2/49 • Number of events 3 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Skin and subcutaneous tissue disorders Hair growth abnormal	8.8% 3/34 • Number of events 3 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Skin and subcutaneous tissue disorders Rash	5.9% 2/34 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Eye disorders Vision blurred	5.9% 2/34 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Gastrointestinal disorders Abdominal pain	5.9% 2/34 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Gastrointestinal disorders Dental caries	5.9% 2/34 • Number of events 3 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	16.7% 3/18 • Number of events 4 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	9.1% 1/11 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Gastrointestinal disorders Diarrhoea	11.8% 4/34 • Number of events 4 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	10.2% 5/49 • Number of events 8 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Gastrointestinal disorders Nausea	11.8% 4/34 • Number of events 5 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	6.1% 3/49 • Number of events 3 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Gastrointestinal disorders Vomiting	8.8% 3/34 • Number of events 3 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	8.2% 4/49 • Number of events 4 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Gastrointestinal disorders Gastrooesophageal reflux disease	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
General disorders Device related thrombosis	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Infections and infestations Bronchitis	5.9% 2/34 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	4.1% 2/49 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	9.1% 1/11 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Infections and infestations Influenza	2.9% 1/34 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	11.1% 2/18 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	20.4% 10/49 • Number of events 10 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Infections and infestations Gastroenteritis	8.8% 3/34 • Number of events 3 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Infections and infestations Herpes virus infection	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Infections and infestations Rhinitis	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Infections and infestations Urinary tract infection	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Eye disorders Cataract	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	9.1% 1/11 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Blood and lymphatic system disorders Anaemia	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Blood and lymphatic system disorders Iron deficiency anaemia	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	6.1% 3/49 • Number of events 3 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Cardiac disorders Arrhythmia	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	9.1% 1/11 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Gastrointestinal disorders Food poisoning	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Gastrointestinal disorders Gastritis	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
General disorders Catheter site pain	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	4.1% 2/49 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
General disorders Influenza like illness	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	9.1% 1/11 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
General disorders Pain	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	4.1% 2/49 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
General disorders Peripheral swelling	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	9.1% 1/11 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Hepatobiliary disorders Drug-induced liver injury	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Immune system disorders Seasonal allergy	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	4.1% 2/49 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Infections and infestations Cellulitis	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	9.1% 1/11 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Infections and infestations Device related infection	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Infections and infestations Lower respiratory tract infection	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Infections and infestations Sinusitis	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	16.7% 3/18 • Number of events 3 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Injury, poisoning and procedural complications Contusion	5.9% 2/34 • Number of events 3 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Injury, poisoning and procedural complications Fall	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	9.1% 1/11 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Injury, poisoning and procedural complications Fibula fracture	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Injury, poisoning and procedural complications Incision site swelling	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Injury, poisoning and procedural complications Ligament sprain	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	9.1% 1/11 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Injury, poisoning and procedural complications Limb injury	5.9% 2/34 • Number of events 3 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	9.1% 1/11 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Injury, poisoning and procedural complications Rib fracture	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Injury, poisoning and procedural complications Skin abrasion	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	18.2% 2/11 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Injury, poisoning and procedural complications Skin laceration	5.9% 2/34 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Injury, poisoning and procedural complications Thermal burn	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	9.1% 1/11 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Injury, poisoning and procedural complications Tooth fracture	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	9.1% 1/11 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Investigations Blood creatine phosphokinase increased	5.9% 2/34 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	6.1% 3/49 • Number of events 4 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	9.1% 1/11 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Investigations Body temperature increased	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	9.1% 1/11 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Investigations C-reactive protein increased	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	9.1% 1/11 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Investigations Indeterminable ABO blood type	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	6.1% 3/49 • Number of events 3 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Investigations Prothrombin fragment 1.2 increased	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	9.1% 1/11 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Metabolism and nutrition disorders Decreased appetite	5.9% 2/34 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Metabolism and nutrition disorders Hypercholesterolaemia	5.9% 2/34 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Musculoskeletal and connective tissue disorders Arthropathy	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	9.1% 1/11 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Musculoskeletal and connective tissue disorders Back pain	5.9% 2/34 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	4.1% 2/49 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Musculoskeletal and connective tissue disorders Groin pain	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	9.1% 1/11 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	4.1% 2/49 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Musculoskeletal and connective tissue disorders Pain in extremity	5.9% 2/34 • Number of events 3 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	8.2% 4/49 • Number of events 4 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Musculoskeletal and connective tissue disorders Plantar fasciitis	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Musculoskeletal and connective tissue disorders Synovitis	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Nervous system disorders Dizziness	11.8% 4/34 • Number of events 4 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	9.1% 1/11 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Nervous system disorders Migraine	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	2.0% 1/49 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Nervous system disorders Neuropathy peripheral	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Product Issues Device occlusion	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	9.1% 1/11 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	9.1% 1/11 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Psychiatric disorders Insomnia	2.9% 1/34 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	4.1% 2/49 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	9.1% 1/11 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Renal and urinary disorders Pollakiuria	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	18.2% 2/11 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	11.8% 4/34 • Number of events 4 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Vascular disorders Hypertension	14.7% 5/34 • Number of events 5 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	6.1% 3/49 • Number of events 3 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	18.2% 2/11 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Skin and subcutaneous tissue disorders Ecchymosis	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	9.1% 1/11 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Skin and subcutaneous tissue disorders Eczema	8.8% 3/34 • Number of events 3 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	9.1% 1/11 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	9.1% 1/11 • Number of events 1 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Skin and subcutaneous tissue disorders Hand dermatitis	5.9% 2/34 • Number of events 3 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Skin and subcutaneous tissue disorders Neurodermatitis	0.00% 0/34 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	5.6% 1/18 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.
Skin and subcutaneous tissue disorders Urticaria	5.9% 2/34 • Number of events 2 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/18 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/49 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.	0.00% 0/11 • From Baseline until study completion (median [min-max] safety observation period for all participants: 133.97 [0.1-249.1] weeks) Safety Population: All treated subjects grouped by treatment (including after up-titration). For Arm B, data collected with episodic bypassing agents (no prophyalxis) for first 24 weeks and with 1.5 mg/kg emicizumab QW after Week 24 are reported separately under Arm B (Control): No Prophylaxis and Arm B (Emi): 1.5 mg/kg Emicizumab QW, respectively.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER