Trial Outcomes & Findings for Pivotal Study (Pharmacokinetics, Efficacy, Safety) of BAX 326 (rFIX) in Hemophilia B Patients (NCT NCT01174446)

NCT ID: NCT01174446

Last Updated: 2021-05-20

Results Overview

Computed using the linear trapezoidal method. The concentration at 72 hours was interpolated from the two nearest sampling time points or extrapolated using the last quantifiable concentration and the terminal rate constant λz. λz was estimated from the slope of natural log-linear fitting to latter quantifiable concentrations, with largest adjusted R\^2.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 86 participants
• Primary outcome timeframe: 72 hours
• Results posted on: 2021-05-20

Participant Flow

Enrollment was conducted at 29 clinical sites in South America, Europe, and Japan.

86 enrolled. 1 withdrew consent prior to randomization. -31 were enrolled and randomized in Parts 1-3. Prior to receiving study drug: 3 discontinued by participant. -Part 2 an additional 54 were enrolled. Prior to receiving study drug: 3 discontinued by participant, 1 withdrew due to an AE, 2 screen failures, and 3 withdrew due to site closure.

Participant milestones

Measure	PK (BAX326 Then BeneFIX) Then Prophylaxis Then PK BAX326 Only -Study Part 1: Pharmacokinetic (PK) Crossover with BAX326 (75 ± 5 IU/kg) then BeneFIX (75 ± 5 IU/kg). -Study Part 2: Open-label evaluation of prophylaxis and on-demand BAX326 only -Study Part 3: Open-label repeat of PK evaluation (repeat Study Part 1) with BAX326 (75 ± 5 IU/kg) only and same study participants as Study Part 1	PK (BeneFIX Then BAX326) Then Prophylaxis Then PK BAX326 Only -Study Part 1: Pharmacokinetic (PK) Crossover with BeneFIX (75 ± 5 IU/kg) then BAX326 (75 ± 5 IU/kg). -Study Part 2: Open-label evaluation of prophylaxis and on-demand BAX326 only -Study Part 3: Open-label repeat of PK evaluation (repeat Study Part 1) with BAX326 (75 ± 5 IU/kg) only and same study participants as Study Part 1	Study Part 2 Only: BAX326 Prophylaxis -Participants were only in Study Part 2 (i.e., did not participate in Study Parts 1 and 3)	Study Part 2 Only: BAX326 On-Demand -Participants were only in Study Part 2 (i.e., did not participate in Study Parts 1 and 3)
Part 1 -Pharmacokinetic Crossover STARTED	14	14	0	0
Part 1 -Pharmacokinetic Crossover COMPLETED	14	14	0	0
Part 1 -Pharmacokinetic Crossover NOT COMPLETED	0	0	0	0
Part 2 -BAX326 Prophylaxis and On-demand STARTED	14	14	31	14
Part 2 -BAX326 Prophylaxis and On-demand COMPLETED	14	14	29	14
Part 2 -BAX326 Prophylaxis and On-demand NOT COMPLETED	0	0	2	0
Part 3 -Pharmacokinetic BAX326 Only STARTED	14	14	0	0
Part 3 -Pharmacokinetic BAX326 Only COMPLETED	13	13	0	0
Part 3 -Pharmacokinetic BAX326 Only NOT COMPLETED	1	1	0	0

Reasons for withdrawal

Measure	PK (BAX326 Then BeneFIX) Then Prophylaxis Then PK BAX326 Only -Study Part 1: Pharmacokinetic (PK) Crossover with BAX326 (75 ± 5 IU/kg) then BeneFIX (75 ± 5 IU/kg). -Study Part 2: Open-label evaluation of prophylaxis and on-demand BAX326 only -Study Part 3: Open-label repeat of PK evaluation (repeat Study Part 1) with BAX326 (75 ± 5 IU/kg) only and same study participants as Study Part 1	PK (BeneFIX Then BAX326) Then Prophylaxis Then PK BAX326 Only -Study Part 1: Pharmacokinetic (PK) Crossover with BeneFIX (75 ± 5 IU/kg) then BAX326 (75 ± 5 IU/kg). -Study Part 2: Open-label evaluation of prophylaxis and on-demand BAX326 only -Study Part 3: Open-label repeat of PK evaluation (repeat Study Part 1) with BAX326 (75 ± 5 IU/kg) only and same study participants as Study Part 1	Study Part 2 Only: BAX326 Prophylaxis -Participants were only in Study Part 2 (i.e., did not participate in Study Parts 1 and 3)	Study Part 2 Only: BAX326 On-Demand -Participants were only in Study Part 2 (i.e., did not participate in Study Parts 1 and 3)
Part 2 -BAX326 Prophylaxis and On-demand Withdrawal by Subject	0	0	1	0
Part 2 -BAX326 Prophylaxis and On-demand Physician Decision	0	0	1	0
Part 3 -Pharmacokinetic BAX326 Only Protocol Violation	1	0	0	0
Part 3 -Pharmacokinetic BAX326 Only Required Emergency Surgery	0	1	0	0

Baseline Characteristics

Pivotal Study (Pharmacokinetics, Efficacy, Safety) of BAX 326 (rFIX) in Hemophilia B Patients

Baseline characteristics by cohort

Measure	All Study Participants Who Received Study Drug n=73 Participants BAX326 : -Study Part 1: Pharmacokinetic (PK) Crossover with BAX326 and BeneFIX -Study Part 2: Open-label evaluation of prophylaxis and on-demand BAX326 only -Study Part 3: Open-label repeat of PK evaluation (repeat Study Part 1) with BAX326 only and same study participants as Study Part 1
Age, Continuous	34.5 years STANDARD_DEVIATION 12.2 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	73 Participants n=5 Participants
Region of Enrollment Spain	1 Participants n=5 Participants
Region of Enrollment Ukraine	8 Participants n=5 Participants
Region of Enrollment Chile	4 Participants n=5 Participants
Region of Enrollment Russian Federation	12 Participants n=5 Participants
Region of Enrollment Colombia	5 Participants n=5 Participants
Region of Enrollment United Kingdom	2 Participants n=5 Participants
Region of Enrollment Czech Republic	2 Participants n=5 Participants
Region of Enrollment Argentina	2 Participants n=5 Participants
Region of Enrollment Brazil	1 Participants n=5 Participants
Region of Enrollment Poland	12 Participants n=5 Participants
Region of Enrollment Romania	8 Participants n=5 Participants
Region of Enrollment Bulgaria	10 Participants n=5 Participants
Region of Enrollment Japan	5 Participants n=5 Participants
Region of Enrollment Sweden	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 72 hours

Population: Pharmacokinetic Per Protocol Analysis Set (PKPPAS) -Participants who participated in Study Parts 1-3 and completed Study Part 1 without any major protocol deviations

Computed using the linear trapezoidal method. The concentration at 72 hours was interpolated from the two nearest sampling time points or extrapolated using the last quantifiable concentration and the terminal rate constant λz. λz was estimated from the slope of natural log-linear fitting to latter quantifiable concentrations, with largest adjusted R^2.

Outcome measures

Measure	On-Demand: End of Study	On-Demand: Change From Baseline	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=25 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=25 Participants	Prophylaxis: Change From Baseline	Part 2 or Part 3: Week 26	Bleeding Cause: Unknown
Study Part 1- Area Under the Plasma Concentration Versus Time Curve From 0 to 72 Hours Per Dose	—	—	14.30 (IU·hr/dL) / (IU/kg) Interval 11.2 to 15.95	13.42 (IU·hr/dL) / (IU/kg) Interval 11.08 to 15.1	—	—	—

SECONDARY outcome

Timeframe: 0-30 minutes before infusion up to 72 hours post-infusion

Population: Pharmacokinetic Per Protocol Analysis Set (PKPPAS) -Participants who participated in Study Parts 1-3 and completed Study Part 1 without any major protocol deviations

Defined as (AUC0-t + Ct)/ λz/ dose, where t is the time of last quantifiable concentration, Ct is the last quantifiable concentration. λz will be estimated from the slope of natural log-linear fitting to latter quantifiable concentrations, with largest adjusted R^2. The objective of Study Part 3 was to re-evaluate the Pharmacokinetic (PK) parameters for BAX 326 after a period of 6 months of treatment, in participants who accumulated at least 30 EDs to BAX 326, and to compare them with those determined in the same participants participating in Study Part 1.

Outcome measures

Measure	On-Demand: End of Study	On-Demand: Change From Baseline	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=25 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=25 Participants	Prophylaxis: Change From Baseline n=23 Participants	Part 2 or Part 3: Week 26	Bleeding Cause: Unknown
Study Parts 1 and 3: Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity Per Dose (AUC0-∞/ Dose)	—	—	16.07 (IU·hr)/ dL/ (IU/kg) Interval 13.43 to 17.48	15.26 (IU·hr)/ dL/ (IU/kg) Interval 13.71 to 17.05	17.38 (IU·hr)/ dL/ (IU/kg) Interval 14.17 to 20.7	—	—

SECONDARY outcome

Timeframe: 0-30 minutes before infusion up to 72 hours post-infusion

Population: Pharmacokinetic Per Protocol Analysis Set (PKPPAS) -Participants who participated in Study Parts 1-3 and completed Study Part 1 without any major protocol deviations

Computed as Area under the moment curve 0-∞ (AUMC0-∞) / AUC0-∞- TI/2, where AUMC0-∞ will be determined in a similar manner as AUC0-∞ and TI represents infusion duration [hr] The objective of Study Part 3 was to re-evaluate the Pharmacokinetic (PK) parameters for BAX 326 after a period of 6 months of treatment, in participants who accumulated at least 30 EDs to BAX 326, and to compare them with those determined in the same participants participating in Study Part 1.

Outcome measures

Measure	On-Demand: End of Study	On-Demand: Change From Baseline	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=25 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=25 Participants	Prophylaxis: Change From Baseline n=23 Participants	Part 2 or Part 3: Week 26	Bleeding Cause: Unknown
Study Parts 1 and 3: Mean Residence Time (MRT)	—	—	28.93 Hour Interval 26.45 to 31.5	30.59 Hour Interval 28.13 to 34.84	29.04 Hour Interval 28.0 to 32.31	—	—

SECONDARY outcome

Timeframe: 0-30 minutes before infusion up to 72 hours post-infusion

Population: Pharmacokinetic Per Protocol Analysis Set (PKPPAS) -Participants who participated in Study Parts 1-3 and completed Study Part 1 without any major protocol deviations

Computed as Dose/ AUC0-∞. The objective of Study Part 3 was to re-evaluate the Pharmacokinetic (PK) parameters for BAX 326 after a period of 6 months of treatment, in participants who accumulated at least 30 EDs to BAX 326, and to compare them with those determined in the same participants participating in Study Part 1.

Outcome measures

Measure	On-Demand: End of Study	On-Demand: Change From Baseline	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=25 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=25 Participants	Prophylaxis: Change From Baseline n=23 Participants	Part 2 or Part 3: Week 26	Bleeding Cause: Unknown
Study Parts 1 and 3: Clearance (CL)	—	—	0.0622 dL/(kg·hr) Interval 0.0572 to 0.0745	0.0655 dL/(kg·hr) Interval 0.0587 to 0.073	0.0576 dL/(kg·hr) Interval 0.0483 to 0.0706	—	—

SECONDARY outcome

Timeframe: 0-30 minutes before infusion up to 1 hour post-infusion

Population: Pharmacokinetic Per Protocol Analysis Set (PKPPAS) -Participants who participated in Study Parts 1-3 and completed Study Part 1 without any major protocol deviations

Defined as (Cmax - Cpre-infusion)/Dose, where maximum concentration (Cmax) will be determined as the highest concentration achieved within one hour after infusion. The objective of Study Part 3 was to re-evaluate the Pharmacokinetic (PK) parameters for BAX 326 after a period of 6 months of treatment, in participants who accumulated at least 30 EDs to BAX 326, and to compare them with those determined in the same participants participating in Study Part 1.

Outcome measures

Measure	On-Demand: End of Study	On-Demand: Change From Baseline	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=25 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=25 Participants	Prophylaxis: Change From Baseline n=23 Participants	Part 2 or Part 3: Week 26	Bleeding Cause: Unknown
Study Parts 1 and 3: Incremental Recovery at Cmax (IR at Cmax)	—	—	0.88 (IU/dL) / (IU/kg) Interval 0.79 to 0.98	0.73 (IU/dL) / (IU/kg) Interval 0.66 to 0.87	0.93 (IU/dL) / (IU/kg) Interval 0.76 to 1.18	—	—

SECONDARY outcome

Timeframe: 0-30 minutes before infusion and 30 minutes post-infusion

Population: Pharmacokinetic Per Protocol Analysis Set (PKPPAS) -Participants who participated in Study Parts 1-3 and completed Study Part 1 without any major protocol deviations

IR at 30 Minutes was measured at the following time points during the study: - Part 1 or Part 2, Exposure Day (ED) 1. (If participant was present for Study Part 1, then ED 1 from Part 1 was used. If Participant entered study in Study Part 2, then ED 1 from Part 2 was used.) - Part 2: Week 5 - Part 2: Week 13 - Part 2 or Part 3: Week 26 (Week 26 of study participation) - Study Completion or Termination Visit

Outcome measures

Measure	On-Demand: End of Study n=23 Participants	On-Demand: Change From Baseline	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=73 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=71 Participants	Prophylaxis: Change From Baseline n=68 Participants	Part 2 or Part 3: Week 26 n=55 Participants	Bleeding Cause: Unknown
Incremental Recovery (IR) at 30 Minutes Over Time	0.89 (IU/dL) / (IU/kg) Interval 0.73 to 0.96	—	0.78 (IU/dL) / (IU/kg) Interval 0.7 to 0.91	0.79 (IU/dL) / (IU/kg) Interval 0.68 to 0.96	0.83 (IU/dL) / (IU/kg) Interval 0.655 to 1.015	0.88 (IU/dL) / (IU/kg) Interval 0.75 to 1.04	—

SECONDARY outcome

Timeframe: 0-30 minutes before infusion and 30 minutes post-infusion

Population: Pharmacokinetic Per Protocol Analysis Set (PKPPAS) -Participants who participated in Study Parts 1-3 and completed Study Part 1 without any major protocol deviations

The median changes in IR at 30 Minutes, calculated as the change in IR value from exposure day 1 (ED1).

Outcome measures

Measure	On-Demand: End of Study	On-Demand: Change From Baseline	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=71 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=68 Participants	Prophylaxis: Change From Baseline n=55 Participants	Part 2 or Part 3: Week 26 n=23 Participants	Bleeding Cause: Unknown
Change in Incremental Recovery (IR) at 30 Minutes Over Time	—	—	0.03 (IU/dL) / (IU/kg) Interval -0.09 to 0.11	0.075 (IU/dL) / (IU/kg) Interval -0.07 to 0.17	0.06 (IU/dL) / (IU/kg) Interval 0.02 to 0.17	0.12 (IU/dL) / (IU/kg) Interval 0.0 to 0.21	—

SECONDARY outcome

Timeframe: 0-30 minutes before infusion up to 72 hours post-infusion

Population: Pharmacokinetic Per Protocol Analysis Set (PKPPAS) -Participants who participated in Study Parts 1-3 and completed Study Part 1 without any major protocol deviations

Elimination phase half-life will be determined as ln2/ λz. The objective of Study Part 3 was to re-evaluate the Pharmacokinetic (PK) parameters for BAX 326 after a period of 6 months of treatment, in participants who accumulated at least 30 EDs to BAX 326, and to compare them with those determined in the same participants participating in Study Part 1.

Outcome measures

Measure	On-Demand: End of Study	On-Demand: Change From Baseline	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=25 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=25 Participants	Prophylaxis: Change From Baseline n=23 Participants	Part 2 or Part 3: Week 26	Bleeding Cause: Unknown
Study Parts 1 and 3: Half Life (T 1/2)	—	—	24.58 Hour Interval 20.98 to 29.68	26.28 Hour Interval 22.51 to 29.46	24.59 Hour Interval 19.68 to 29.14	—	—

SECONDARY outcome

Timeframe: 0-30 minutes before infusion up to 72 hours post-infusion

Population: Pharmacokinetic Per Protocol Analysis Set (PKPPAS) -Participants who participated in Study Parts 1-3 and completed Study Part 1 without any major protocol deviations

Vss computed as CL·MRT. The objective of Study Part 3 was to re-evaluate the Pharmacokinetic (PK) parameters for BAX 326 after a period of 6 months of treatment, in participants who accumulated at least 30 EDs to BAX 326, and to compare them with those determined in the same participants participating in Study Part 1.

Outcome measures

Measure	On-Demand: End of Study	On-Demand: Change From Baseline	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=25 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=25 Participants	Prophylaxis: Change From Baseline n=23 Participants	Part 2 or Part 3: Week 26	Bleeding Cause: Unknown
Study Parts 1 and 3: Volume of Distribution at Steady State (Vss)	—	—	1.72 dL/kg Interval 1.56 to 2.3	1.98 dL/kg Interval 1.76 to 2.51	1.74 dL/kg Interval 1.49 to 2.05	—	—

SECONDARY outcome

Timeframe: Study Part 2 = 26 weeks ± 1 week (Note: Study Part 1 = 2-4 weeks)

Population: Full Analysis Set - Prophylactic cohort

ABR during prophylaxis (twice-weekly) in Part 2 was calculated as (Number of bleeding episodes/observed treatment period in days) * 365.25. The treatment period on prophylaxis was defined as time between the first and the last prophylactic infusions and ABR on prophylaxis was calculated for participants who received a minimum of 3 months of prophylactic treatment with BAX326.

Outcome measures

Measure	On-Demand: End of Study	On-Demand: Change From Baseline	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=56 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study	Prophylaxis: Change From Baseline	Part 2 or Part 3: Week 26	Bleeding Cause: Unknown
Study Part 2: Annualized Bleed Rate (ABR) During Treatment With BAX326 Joint bleeding episode	—	—	0.00 Bleeds per year Interval 0.0 to 4.5	—	—	—	—
Study Part 2: Annualized Bleed Rate (ABR) During Treatment With BAX326 Non-Joint bleeding episode	—	—	0.00 Bleeds per year Interval 0.0 to 2.0	—	—	—	—
Study Part 2: Annualized Bleed Rate (ABR) During Treatment With BAX326 Spontaneous bleeding episode	—	—	0.00 Bleeds per year Interval 0.0 to 2.0	—	—	—	—
Study Part 2: Annualized Bleed Rate (ABR) During Treatment With BAX326 Bleeding episode caused by injury	—	—	0.00 Bleeds per year Interval 0.0 to 2.1	—	—	—	—
Study Part 2: Annualized Bleed Rate (ABR) During Treatment With BAX326 Unknown cause of bleeding episode	—	—	0.00 Bleeds per year Interval 0.0 to 0.0	—	—	—	—
Study Part 2: Annualized Bleed Rate (ABR) During Treatment With BAX326 All bleeding episodes	—	—	1.99 Bleeds per year Interval 0.0 to 6.5	—	—	—	—

SECONDARY outcome

Timeframe: Study Part 2 = 26 weeks ± 1 week (Study Part 2 began at week 3-5)

Population: Full Analysis Set

The number of bleeding episodes treated with 1, 2, or ≥3 infusions of BAX326 to achieve adequate hemostasis. Only infusions required until resolution of bleed were considered.

Outcome measures

Measure	On-Demand: End of Study n=130 bleeding episodes	On-Demand: Change From Baseline n=90 bleeding episodes	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=107 bleeding episodes Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=90 bleeding episodes	Prophylaxis: Change From Baseline n=197 bleeding episodes	Part 2 or Part 3: Week 26 n=52 bleeding episodes	Bleeding Cause: Unknown n=29 bleeding episodes
Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326 by Bleeding Site and Cause 1 infusion	84 Bleeding episodes	50 Bleeding episodes	65 Bleeding episodes	57 Bleeding episodes	122 Bleeding episodes	31 Bleeding episodes	19 Bleeding episodes
Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326 by Bleeding Site and Cause 2 infusions	29 Bleeding episodes	24 Bleeding episodes	26 Bleeding episodes	21 Bleeding episodes	47 Bleeding episodes	11 Bleeding episodes	5 Bleeding episodes
Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326 by Bleeding Site and Cause 3 or more infusions	17 Bleeding episodes	16 Bleeding episodes	16 Bleeding episodes	12 Bleeding episodes	28 Bleeding episodes	10 Bleeding episodes	5 Bleeding episodes

SECONDARY outcome

Timeframe: At bleed resolution throughout the study period of 22 months (Study Parts 1, 2, and 3)

Population: Full Analysis Set

Rating Scale for Treatment of BEs (4-point ordinal scale): -Excellent: Full relief of pain and cessation of objective signs of bleeding (eg, swelling, tenderness, and decreased range of motion in the case of musculoskeletal hemorrhage) after a single infusion. No additional infusion required for the control of bleeding. Administration of further infusions to maintain hemostasis did not affect this scoring. -Good: Definite pain relief and/or improvement in signs of bleeding after a single infusion. Possibly requires more than 1 infusion for complete resolution. -Fair: Probable and/or slight relief of pain and slight improvement in signs of bleeding after single infusion. Required more than 1 infusion for complete resolution. -None: No improvement or condition worsens.

Outcome measures

Measure	On-Demand: End of Study n=130 Bleeding episodes	On-Demand: Change From Baseline n=90 Bleeding episodes	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=107 Bleeding episodes Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=90 Bleeding episodes	Prophylaxis: Change From Baseline n=197 Bleeding episodes	Part 2 or Part 3: Week 26 n=52 Bleeding episodes	Bleeding Cause: Unknown n=29 Bleeding episodes
Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause Excellent	51 Bleeding episodes	40 Bleeding episodes	53 Bleeding episodes	32 Bleeding episodes	85 Bleeding episodes	17 Bleeding episodes	11 Bleeding episodes
Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause Good	75 Bleeding episodes	45 Bleeding episodes	46 Bleeding episodes	57 Bleeding episodes	103 Bleeding episodes	34 Bleeding episodes	17 Bleeding episodes
Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause Fair	2 Bleeding episodes	2 Bleeding episodes	5 Bleeding episodes	0 Bleeding episodes	5 Bleeding episodes	0 Bleeding episodes	1 Bleeding episodes
Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause None	0 Bleeding episodes	0 Bleeding episodes	0 Bleeding episodes	0 Bleeding episodes	0 Bleeding episodes	0 Bleeding episodes	0 Bleeding episodes
Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause Not Reported	2 Bleeding episodes	3 Bleeding episodes	3 Bleeding episodes	1 Bleeding episodes	4 Bleeding episodes	1 Bleeding episodes	0 Bleeding episodes

SECONDARY outcome

Timeframe: Study Part 2 = 26 weeks ± 1 week (Note: Study Part 1 = 2-4 weeks)

Population: Full Analysis Set

Outcome measures

Measure	On-Demand: End of Study n=130 Bleeding Episodes	On-Demand: Change From Baseline n=90 Bleeding Episodes	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=107 Bleeding Episodes Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=90 Bleeding Episodes	Prophylaxis: Change From Baseline n=197 Bleeding Episodes	Part 2 or Part 3: Week 26 n=52 Bleeding Episodes	Bleeding Cause: Unknown n=29 Bleeding Episodes
Total Weight-adjusted Dose Per Bleeding Episode (BEs) of All BEs Treated With BAX326 by Bleeding Site and Cause	52.3 IU/kg Interval 45.0 to 92.0	70.0 IU/kg Interval 48.0 to 116.0	56.5 IU/kg Interval 48.0 to 97.0	59.0 IU/kg Interval 46.0 to 97.0	56.5 IU/kg Interval 47.0 to 97.0	68.7 IU/kg Interval 50.0 to 130.0	56.5 IU/kg Interval 51.0 to 108.0

SECONDARY outcome

Timeframe: Study Part 2 = 26 weeks ± 1 week (Note: Study Part 1 = 2-4 weeks)

Population: Full Analysis Set

Weight-adjusted consumption of BAX326 by event per participant, i.e., for prophylactic treatment and for treatment of bleeds until resolution of bleed.

Outcome measures

Measure	On-Demand: End of Study	On-Demand: Change From Baseline	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=59 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=47 Participants	Prophylaxis: Change From Baseline	Part 2 or Part 3: Week 26	Bleeding Cause: Unknown
Consumption of BAX326 Per Event Per Participant	—	—	50.5 IU/kg Interval 46.0 to 52.0	87.1 IU/kg Interval 56.0 to 125.0	—	—	—

SECONDARY outcome

Timeframe: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week (Prophylaxis and On-Demand period), Study Part 3 = 1 week (Total = 29-31 weeks)

Population: Full Analysis Set

Outcome measures

Measure	On-Demand: End of Study	On-Demand: Change From Baseline	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=59 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=14 Participants	Prophylaxis: Change From Baseline	Part 2 or Part 3: Week 26	Bleeding Cause: Unknown
Consumption of BAX326 Per Participant: Median Number of Infusions Per Month	—	—	6.7 Infusions Interval 6.0 to 7.0	2.7 Infusions Interval 2.0 to 4.0	—	—	—

SECONDARY outcome

Timeframe: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week (Prophylaxis and On-Demand period), Study Part 3 = 1 week (Total = 29-31 weeks)

Population: Full Analysis Set

Outcome measures

Measure	On-Demand: End of Study	On-Demand: Change From Baseline	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=59 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=14 Participants	Prophylaxis: Change From Baseline	Part 2 or Part 3: Week 26	Bleeding Cause: Unknown
Consumption of BAX326 Per Participant: Median Weight-adjusted Consumption Per Month	—	—	347.8 IU/kg Interval 320.0 to 396.0	167.3 IU/kg Interval 102.0 to 234.0	—	—	—

SECONDARY outcome

Timeframe: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

Population: Full Analysis Set

Outcome measures

Measure	On-Demand: End of Study	On-Demand: Change From Baseline	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=73 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study	Prophylaxis: Change From Baseline	Part 2 or Part 3: Week 26	Bleeding Cause: Unknown
Number of Participants Who Developed Inhibitory Antibodies to Factor IX (FIX)	—	—	0 participants	—	—	—	—

SECONDARY outcome

Timeframe: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

Population: Full Analysis Set

Occurrence of total binding antibodies of indeterminate specificity (within assay variability) to FIX, antibodies to CHO proteins and rFurin is defined by a dilution of 2 or less increase as compared to levels at screening visit (e.g. negative to 1:20 or 1:40).

Outcome measures

Measure	On-Demand: End of Study	On-Demand: Change From Baseline	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=73 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study	Prophylaxis: Change From Baseline	Part 2 or Part 3: Week 26	Bleeding Cause: Unknown
Occurrence of Total Binding Antibodies of Indeterminate Specificity (Within Assay Variability) Binding Antibody to Factor IX (FIX)	—	—	6 participants	—	—	—	—
Occurrence of Total Binding Antibodies of Indeterminate Specificity (Within Assay Variability) Antibody to Chinese hamster ovary (CHO) Protein	—	—	0 participants	—	—	—	—
Occurrence of Total Binding Antibodies of Indeterminate Specificity (Within Assay Variability) Antibody to recombinant Furin (rFurin)	—	—	9 participants	—	—	—	—

SECONDARY outcome

Timeframe: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

Population: Full Analysis Set

Occurrence of treatment related total binding antibodies to Factor IX (FIX), antibodies to Chinese hamster ovary (CHO) proteins, and recombinant furin (rFurin) is defined by more than 2-dilution increase as compared to levels at screening visit and confirmed specificity (e.g. negative to 1:80)

Outcome measures

Measure	On-Demand: End of Study	On-Demand: Change From Baseline	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=73 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study	Prophylaxis: Change From Baseline	Part 2 or Part 3: Week 26	Bleeding Cause: Unknown
Occurrence of Treatment Related Total Binding Antibodies Binding Antibody to Factor IX (FIX)	—	—	0 participants	—	—	—	—
Occurrence of Treatment Related Total Binding Antibodies Antibody to Chinese hamster ovary (CHO) Protein	—	—	0 participants	—	—	—	—
Occurrence of Treatment Related Total Binding Antibodies Antibody to recombinant Furin (rFurin)	—	—	0 participants	—	—	—	—

SECONDARY outcome

Timeframe: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

Population: Full Analysis Set

Outcome measures

Measure	On-Demand: End of Study	On-Demand: Change From Baseline	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=73 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study	Prophylaxis: Change From Baseline	Part 2 or Part 3: Week 26	Bleeding Cause: Unknown
Number of Participants Who Experienced Severe Allergic Reactions (e.g. Anaphylaxis)	—	—	0 participants	—	—	—	—

SECONDARY outcome

Timeframe: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

Population: Full Analysis Set

Outcome measures

Measure	On-Demand: End of Study	On-Demand: Change From Baseline	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=73 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study	Prophylaxis: Change From Baseline	Part 2 or Part 3: Week 26	Bleeding Cause: Unknown
Number of Participants Who Experienced Thrombotic Events	—	—	0 participants	—	—	—	—

SECONDARY outcome

Timeframe: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

Population: Full Analysis Set

Clinically significant changes in chemistry assessments for Alanine Aminotransferase, Albumin, Alkaline Phosphatase, Aspartate Aminotransferase, Bicarbonate, Bilirubin, Blood Urea Nitrogen, Chloride, Glucose, Potassium, Protein (Serum), Sodium. Clinically Significant (CS) defined as: -1. The abnormal value constitutes an adverse event (AE) and, -2. The abnormal value is a symptom of or related to a disease that is already recorded as an AE in Case Report Form (CRF).

Outcome measures

Measure	On-Demand: End of Study	On-Demand: Change From Baseline	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=73 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study	Prophylaxis: Change From Baseline	Part 2 or Part 3: Week 26	Bleeding Cause: Unknown
Number of Participants With Clinically Significant Changes in Laboratory Parameters: Clinical Chemistry	—	—	0 participants	—	—	—	—

SECONDARY outcome

Timeframe: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

Population: Full Analysis Set

Clinically significant changes in hematology assessments for Basophils, Basophils/Leukocytes, Eosinophils, Eosinophils/Leukocytes, Erythrocyte Mean Corpuscular Hemoglobin Concentration, Erythrocyte Mean Corpuscular Volume, Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Lymphocytes/Leukocytes, Monocytes, Monocytes/Leukocytes, Neutrophils, Neutrophils/Leukocytes, Platelets,

Outcome measures

Measure	On-Demand: End of Study	On-Demand: Change From Baseline	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=73 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study	Prophylaxis: Change From Baseline	Part 2 or Part 3: Week 26	Bleeding Cause: Unknown
Number of Participants With Clinically Significant Changes in Laboratory Parameters: Hematology	—	—	0 participants	—	—	—	—

SECONDARY outcome

Timeframe: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

Population: Full Analysis Set

Clinically significant changes in vital signs assessments for pulse rate, systolic/diastolic blood pressure, respiratory rate, body temperature

Outcome measures

Measure	On-Demand: End of Study	On-Demand: Change From Baseline	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=73 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study	Prophylaxis: Change From Baseline	Part 2 or Part 3: Week 26	Bleeding Cause: Unknown
Number of Participants With Clinically Significant Changes in Laboratory Parameters: Vital Signs	—	—	0 participants	—	—	—	—

SECONDARY outcome

Timeframe: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

Population: Full Analysis Set

Clinically significant changes in thrombogenic markers assessments for thrombin-antithrombin (TAT), prothrombin fragment 1.2, and D-dimer as evaluated by an independent Data Monitoring Committee (DMC)

Outcome measures

Measure	On-Demand: End of Study	On-Demand: Change From Baseline	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=73 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study	Prophylaxis: Change From Baseline	Part 2 or Part 3: Week 26	Bleeding Cause: Unknown
Number of Participants With Clinically Significant Changes in Laboratory Parameters: Thrombogenic Markers	—	—	0 participants	—	—	—	—

SECONDARY outcome

Timeframe: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, and Study Part 3 = 1 week (Total = 29-31 weeks)

Population: Full Analysis Set

Outcome measures

Measure	On-Demand: End of Study	On-Demand: Change From Baseline	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=73 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=73 Participants	Prophylaxis: Change From Baseline	Part 2 or Part 3: Week 26	Bleeding Cause: Unknown
Number of Adverse Events (AEs) After BAX326 Treatment Serious- Mild	—	—	1 adverse events	0 adverse events	—	—	—
Number of Adverse Events (AEs) After BAX326 Treatment Serious- Moderate	—	—	1 adverse events	0 adverse events	—	—	—
Number of Adverse Events (AEs) After BAX326 Treatment Serious- Severe	—	—	3 adverse events	0 adverse events	—	—	—
Number of Adverse Events (AEs) After BAX326 Treatment Serious- Unknown	—	—	0 adverse events	0 adverse events	—	—	—
Number of Adverse Events (AEs) After BAX326 Treatment Non-Serious- Mild	—	—	63 adverse events	2 adverse events	—	—	—
Number of Adverse Events (AEs) After BAX326 Treatment Non-Serious- Moderate	—	—	17 adverse events	0 adverse events	—	—	—
Number of Adverse Events (AEs) After BAX326 Treatment Non-Serious- Severe	—	—	1 adverse events	0 adverse events	—	—	—
Number of Adverse Events (AEs) After BAX326 Treatment Non-Serious- Unknown	—	—	1 adverse events	1 adverse events	—	—	—

SECONDARY outcome

Timeframe: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, and Study Part 3 = 1 week (Total = 29-31 weeks)

Outcome measures

Measure	On-Demand: End of Study	On-Demand: Change From Baseline	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=73 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=73 Participants	Prophylaxis: Change From Baseline	Part 2 or Part 3: Week 26	Bleeding Cause: Unknown
Number of Participants With Adverse Events (AEs) After BAX326 Treatment Serious- Severe	—	—	2 participants	0 participants	—	—	—
Number of Participants With Adverse Events (AEs) After BAX326 Treatment Serious- Unknown	—	—	0 participants	0 participants	—	—	—
Number of Participants With Adverse Events (AEs) After BAX326 Treatment Non-Serious- Mild	—	—	33 participants	1 participants	—	—	—
Number of Participants With Adverse Events (AEs) After BAX326 Treatment Non-Serious- Moderate	—	—	9 participants	0 participants	—	—	—
Number of Participants With Adverse Events (AEs) After BAX326 Treatment Non-Serious- Severe	—	—	1 participants	0 participants	—	—	—
Number of Participants With Adverse Events (AEs) After BAX326 Treatment Non-Serious- Unknown	—	—	1 participants	1 participants	—	—	—
Number of Participants With Adverse Events (AEs) After BAX326 Treatment Serious- Mild	—	—	1 participants	0 participants	—	—	—
Number of Participants With Adverse Events (AEs) After BAX326 Treatment Serious- Moderate	—	—	1 participants	0 participants	—	—	—

SECONDARY outcome

Timeframe: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

Population: Full Analysis Set

EQ-5D is a participant answered questionnaire scoring 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ-5D total score ranges from 0 (worst health state) to 1 (perfect health state) and 1 reflects the best outcome.

Outcome measures

Measure	On-Demand: End of Study n=14 Participants	On-Demand: Change From Baseline n=14 Participants	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=56 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=55 Participants	Prophylaxis: Change From Baseline n=55 Participants	Part 2 or Part 3: Week 26 n=14 Participants	Bleeding Cause: Unknown
EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) Total Index Scores	0.73 Score on a scale Standard Deviation 0.09	0.00 Score on a scale Standard Deviation 0.13	0.75 Score on a scale Standard Deviation 0.16 • Interval 0.7 to 0.8	0.75 Score on a scale Standard Deviation 0.16 • Interval 0.7 to 0.8	0.01 Score on a scale Standard Deviation 0.18 • Interval -0.1 to 0.1	0.72 Score on a scale Standard Deviation 0.14	—

SECONDARY outcome

Timeframe: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

Population: Full Analysis Set

Participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better quality of life.

Outcome measures

Measure	On-Demand: End of Study n=14 Participants	On-Demand: Change From Baseline n=14 Participants	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=56 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=54 Participants	Prophylaxis: Change From Baseline n=54 Participants	Part 2 or Part 3: Week 26 n=14 Participants	Bleeding Cause: Unknown
EuroQoL (Quality of Life)-5 Dimensions Visual Analogue Scale (EQ-5D VAS) Scores	62.07 Score on a scale Standard Deviation 19.00	5.43 Score on a scale Standard Deviation 24.02	58.75 Score on a scale Standard Deviation 24.89 • Interval 50.0 to 75.0	68.22 Score on a scale Standard Deviation 22.78 • Interval 60.0 to 85.0	9.98 Score on a scale Standard Deviation 25.41 • Interval -2.0 to 20.0	56.64 Score on a scale Standard Deviation 25.97	—

SECONDARY outcome

Timeframe: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

Population: Full Analysis Set

Participant rated assessment of health-related quality of life. The VAS Pain Scale rates current health state on a scale from 0 (no pain) to 100 (worst imaginable pain). For the pain scale, a higher score indicates worse pain.

Outcome measures

Measure	On-Demand: End of Study n=14 Participants	On-Demand: Change From Baseline n=14 Participants	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=55 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=55 Participants	Prophylaxis: Change From Baseline n=54 Participants	Part 2 or Part 3: Week 26 n=14 Participants	Bleeding Cause: Unknown
General Pain Assessment Through a Visual Analog Scale (VAS)	39.93 Score on a scale Standard Deviation 22.57	-7.64 Score on a scale Standard Deviation 33.58	32.67 Score on a scale Standard Deviation 26.62	33.09 Score on a scale Standard Deviation 25.90	0.35 Score on a scale Standard Deviation 21.77	47.57 Score on a scale Standard Deviation 30.82	—

SECONDARY outcome

Timeframe: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

Population: Full Analysis Set

The PCS is a summary scale of the dimensions physical functioning, role physical, bodily pain, and general health. The component score is normalized to a standard population. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores.

Outcome measures

Measure	On-Demand: End of Study n=13 Participants	On-Demand: Change From Baseline n=13 Participants	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=54 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=52 Participants	Prophylaxis: Change From Baseline n=52 Participants	Part 2 or Part 3: Week 26 n=13 Participants	Bleeding Cause: Unknown
Short Form (36) Health Survey (SF-36): HRQoL 'Physical Component Score' (PCS)	38.92 Score on a scale Standard Deviation 8.53	1.54 Score on a scale Standard Deviation 5.11	39.08 Score on a scale Standard Deviation 9.39	41.35 Score on a scale Standard Deviation 8.73	2.60 Score on a scale Standard Deviation 7.72	37.38 Score on a scale Standard Deviation 7.20	—

SECONDARY outcome

Timeframe: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

Population: Full Analysis Set

Quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores.

Outcome measures

Measure	On-Demand: End of Study n=13 Participants	On-Demand: Change From Baseline n=13 Participants	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=54 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=52 Participants	Prophylaxis: Change From Baseline n=52 Participants	Part 2 or Part 3: Week 26 n=13 Participants	Bleeding Cause: Unknown
SF-36: HRQoL 'Mental Health' (MH)	45.03 Score on a scale Standard Deviation 9.96	-2.21 Score on a scale Standard Deviation 8.28	47.53 Score on a scale Standard Deviation 9.46	49.67 Score on a scale Standard Deviation 9.30	2.01 Score on a scale Standard Deviation 11.17	47.24 Score on a scale Standard Deviation 8.80	—

SECONDARY outcome

Timeframe: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

Population: Full Analysis Set

Quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores.

Outcome measures

Measure	On-Demand: End of Study n=13 Participants	On-Demand: Change From Baseline n=13 Participants	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=54 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=53 Participants	Prophylaxis: Change From Baseline n=53 Participants	Part 2 or Part 3: Week 26 n=13 Participants	Bleeding Cause: Unknown
SF-36: HRQoL Physical Functioning' (PF)	39.87 Score on a scale Standard Deviation 10.55	-0.16 Score on a scale Standard Deviation 5.86	40.20 Score on a scale Standard Deviation 10.57	40.75 Score on a scale Standard Deviation 10.14	0.68 Score on a scale Standard Deviation 7.48	40.04 Score on a scale Standard Deviation 10.57	—

SECONDARY outcome

Timeframe: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

Population: Full Analysis Set

Quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores.

Outcome measures

Measure	On-Demand: End of Study n=13 Participants	On-Demand: Change From Baseline n=13 Participants	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=54 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=53 Participants	Prophylaxis: Change From Baseline n=53 Participants	Part 2 or Part 3: Week 26 n=13 Participants	Bleeding Cause: Unknown
SF-36: HRQoL Role-Physical (RP)	37.45 Score on a scale Standard Deviation 10.12	-1.70 Score on a scale Standard Deviation 5.86	40.39 Score on a scale Standard Deviation 10.70	43.82 Score on a scale Standard Deviation 8.67	3.47 Score on a scale Standard Deviation 10.15	39.15 Score on a scale Standard Deviation 8.13	—

SECONDARY outcome

Timeframe: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

Population: Full Analysis Set

Quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores.

Outcome measures

Measure	On-Demand: End of Study n=13 Participants	On-Demand: Change From Baseline n=13 Participants	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=54 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=53 Participants	Prophylaxis: Change From Baseline n=53 Participants	Part 2 or Part 3: Week 26 n=13 Participants	Bleeding Cause: Unknown
SF-36: HRQoL Role-Emotional	39.43 Score on a scale Standard Deviation 11.57	-1.50 Score on a scale Standard Deviation 8.91	44.22 Score on a scale Standard Deviation 11.45	44.80 Score on a scale Standard Deviation 10.15	0.37 Score on a scale Standard Deviation 11.74	40.93 Score on a scale Standard Deviation 9.10	—

SECONDARY outcome

Timeframe: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

Population: Full Analysis Set

Quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores.

Outcome measures

Measure	On-Demand: End of Study n=13 Participants	On-Demand: Change From Baseline n=13 Participants	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=54 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=53 Participants	Prophylaxis: Change From Baseline n=53 Participants	Part 2 or Part 3: Week 26 n=13 Participants	Bleeding Cause: Unknown
SF-36: HRQoL Bodily Pain	39.33 Score on a scale Standard Deviation 8.91	2.44 Score on a scale Standard Deviation 10.18	42.09 Score on a scale Standard Deviation 10.21	45.72 Score on a scale Standard Deviation 8.68	3.45 Score on a scale Standard Deviation 9.95	36.89 Score on a scale Standard Deviation 7.84	—

SECONDARY outcome

Timeframe: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

Population: Full Analysis Set

Quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores.

Outcome measures

Measure	On-Demand: End of Study n=13 Participants	On-Demand: Change From Baseline n=13 Participants	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=54 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=52 Participants	Prophylaxis: Change From Baseline n=52 Participants	Part 2 or Part 3: Week 26 n=13 Participants	Bleeding Cause: Unknown
SF-36: HRQoL Mental Health	42.64 Score on a scale Standard Deviation 10.63	-2.82 Score on a scale Standard Deviation 8.53	45.52 Score on a scale Standard Deviation 8.78	47.95 Score on a scale Standard Deviation 8.84	2.44 Score on a scale Standard Deviation 11.29	45.46 Score on a scale Standard Deviation 10.57	—

SECONDARY outcome

Timeframe: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

Population: Full Analysis Set

Quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores.

Outcome measures

Measure	On-Demand: End of Study n=13 Participants	On-Demand: Change From Baseline n=13 Participants	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=54 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=52 Participants	Prophylaxis: Change From Baseline n=52 Participants	Part 2 or Part 3: Week 26 n=13 Participants	Bleeding Cause: Unknown
SF-36: HRQoL Vitality	50.89 Score on a scale Standard Deviation 6.81	0.72 Score on a scale Standard Deviation 5.43	50.07 Score on a scale Standard Deviation 8.47	52.75 Score on a scale Standard Deviation 8.88	2.46 Score on a scale Standard Deviation 10.75	50.17 Score on a scale Standard Deviation 5.63	—

SECONDARY outcome

Timeframe: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

Population: Full Analysis Set

Quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores.

Outcome measures

Measure	On-Demand: End of Study n=13 Participants	On-Demand: Change From Baseline n=13 Participants	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=54 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=53 Participants	Prophylaxis: Change From Baseline n=53 Participants	Part 2 or Part 3: Week 26 n=13 Participants	Bleeding Cause: Unknown
SF-36: HRQoL Social Functioning	42.17 Score on a scale Standard Deviation 9.80	-1.26 Score on a scale Standard Deviation 6.36	41.80 Score on a scale Standard Deviation 10.54	44.60 Score on a scale Standard Deviation 8.94	2.78 Score on a scale Standard Deviation 10.78	43.42 Score on a scale Standard Deviation 9.61	—

SECONDARY outcome

Timeframe: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

Population: Full Analysis Set

Quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores.

Outcome measures

Measure	On-Demand: End of Study n=13 Participants	On-Demand: Change From Baseline n=13 Participants	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=54 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=53 Participants	Prophylaxis: Change From Baseline n=53 Participants	Part 2 or Part 3: Week 26 n=13 Participants	Bleeding Cause: Unknown
SF-36: HRQoL General Health	39.07 Score on a scale Standard Deviation 8.88	1.98 Score on a scale Standard Deviation 7.94	37.84 Score on a scale Standard Deviation 8.38	39.98 Score on a scale Standard Deviation 9.03	2.20 Score on a scale Standard Deviation 8.22	37.09 Score on a scale Standard Deviation 10.47	—

SECONDARY outcome

Timeframe: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

Population: Full Analysis Set

The Peds-QL is a generic Health-Related Quality of Life (HR QoL) instrument designed specifically for a pediatric population. It captures the following domains: general health/activities, feelings/emotional, social functioning, school functioning. For this study, the Peds-QL for 12 to 16-year-old subjects was used. Higher scores indicate better quality of life (QOL) for all domains of the Peds-QL. This modular instrument uses a 5-point scale: from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. 4 dimensions (physical, emotional, social, & school functioning) are scored.

Outcome measures

Measure	On-Demand: End of Study n=1 Participants	On-Demand: Change From Baseline n=1 Participants	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=2 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=2 Participants	Prophylaxis: Change From Baseline n=2 Participants	Part 2 or Part 3: Week 26 n=1 Participants	Bleeding Cause: Unknown
Pediatric Quality of Life Questionnaire (PedsQL) Physical Health Summary Score (Ages 12-16)	65.63 Score on a scale Standard Deviation NA Sample size = 1, therefore not possible to calculate a standard deviation.	0.00 Score on a scale Standard Deviation NA Sample size = 1, therefore not possible to calculate a standard deviation.	65.63 Score on a scale Standard Deviation 13.26	54.69 Score on a scale Standard Deviation 6.63	-10.94 Score on a scale Standard Deviation 19.89	65.63 Score on a scale Standard Deviation NA Sample size = 1, therefore not possible to calculate a standard deviation.	—

SECONDARY outcome

Timeframe: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

Population: Full Analysis Set

The Peds-QL is a generic Health-Related Quality of Life (HR QoL) instrument designed specifically for a pediatric population. It captures the following domains: general health/activities, feelings/emotional, social functioning, school functioning. For this study, the Peds-QL for 12 to 16-year-old subjects was used. Higher scores indicate better quality of life (QOL) for all domains of the Peds-QL. This modular instrument uses a 5-point scale: from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. 4 dimensions (physical, emotional, social, & school functioning) are scored.

Outcome measures

Measure	On-Demand: End of Study n=1 Participants	On-Demand: Change From Baseline n=1 Participants	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=2 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=2 Participants	Prophylaxis: Change From Baseline n=2 Participants	Part 2 or Part 3: Week 26 n=1 Participants	Bleeding Cause: Unknown
Pediatric Quality of Life Questionnaire (PedsQL) Psychosocial Health Summary Score (Ages 12-16)	86.67 Score on a scale Standard Deviation NA Sample size = 1, therefore not possible to calculate a standard deviation.	-1.67 Score on a scale Standard Deviation NA Sample size = 1, therefore not possible to calculate a standard deviation.	63.33 Score on a scale Standard Deviation 11.79	55.83 Score on a scale Standard Deviation 3.54	-7.50 Score on a scale Standard Deviation 8.25	88.33 Score on a scale Standard Deviation NA Sample size = 1, therefore not possible to calculate a standard deviation.	—

SECONDARY outcome

Timeframe: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

Population: Full Analysis Set

The Peds-QL is a generic Health-Related Quality of Life (HR QoL) instrument designed specifically for a pediatric population. It captures the following domains: general health/activities, feelings/emotional, social functioning, school functioning. For this study, the Peds-QL for 12 to 16-year-old subjects was used. Higher scores indicate better quality of life (QOL) for all domains of the Peds-QL. This modular instrument uses a 5-point scale: from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. 4 dimensions (physical, emotional, social, & school functioning) are scored.

Outcome measures

Measure	On-Demand: End of Study n=1 Participants	On-Demand: Change From Baseline n=1 Participants	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=2 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=2 Participants	Prophylaxis: Change From Baseline n=2 Participants	Part 2 or Part 3: Week 26 n=1 Participants	Bleeding Cause: Unknown
Pediatric Quality of Life Questionnaire (PedsQL) Total Score (Ages 12-16)	79.35 Score on a scale Standard Deviation NA Sample size = 1, therefore not possible to calculate a standard deviation.	-1.09 Score on a scale Standard Deviation NA Sample size = 1, therefore not possible to calculate a standard deviation.	64.13 Score on a scale Standard Deviation 12.30	55.43 Score on a scale Standard Deviation 0.00	-8.70 Score on a scale Standard Deviation 12.30	80.43 Score on a scale Standard Deviation NA Sample size = 1, therefore not possible to calculate a standard deviation.	—

SECONDARY outcome

Timeframe: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

Population: Full Analysis Set

The Haem-A-QOL instrument has been developed and used in hemophilia A patients. As a hemophilia-specific instrument, this measure assesses very specific aspects of dealing with hemophilia. The areas covered by this instrument are: physical health, sports/leisure, school/work, dealing with hemophilia, and outlook for the future. For the Haem-A-QOL, higher scores indicate a worse quality of life. Scores on a scale range between 0 and 100.

Outcome measures

Measure	On-Demand: End of Study n=13 Participants	On-Demand: Change From Baseline n=13 Participants	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=51 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=50 Participants	Prophylaxis: Change From Baseline n=48 Participants	Part 2 or Part 3: Week 26 n=13 Participants	Bleeding Cause: Unknown
Health-Related Quality of Life (HRQoL) Disease-specific: Haem-A-QoL	41.37 Score on a scale Standard Deviation 16.64	-0.28 Score on a scale Standard Deviation 12.18	40.68 Score on a scale Standard Deviation 15.33	37.85 Score on a scale Standard Deviation 16.57	-3.52 Score on a scale Standard Deviation 12.81	41.65 Score on a scale Standard Deviation 15.19	—

SECONDARY outcome

Timeframe: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

Population: Full Analysis Set

The Haemo-QoL is a quality of life (QoL) assessment instrument for children and adolescents with haemophilia. As a hemophilia-specific instrument, this measure assesses very specific aspects of dealing with hemophilia. For the Haemo-QoL, higher scores indicate a worse quality of life. Scores on a scale range between 0 and 100.

Outcome measures

Measure	On-Demand: End of Study	On-Demand: Change From Baseline	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=1 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=1 Participants	Prophylaxis: Change From Baseline n=1 Participants	Part 2 or Part 3: Week 26	Bleeding Cause: Unknown
Health-Related Quality of Life (HRQoL) Disease-specific: Haemo-QoL - Participants On-Demand (Ages 12-16)	—	—	40.00 Score on a scale Standard Deviation NA Sample size = 1, therefore not possible to calculate a standard deviation.	40.00 Score on a scale Standard Deviation NA Sample size = 1, therefore not possible to calculate a standard deviation.	0.00 Score on a scale Standard Deviation NA Sample size = 1, therefore not possible to calculate a standard deviation.	—	—

SECONDARY outcome

Timeframe: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

Population: Full Analysis Set

Outcome measures

Measure	On-Demand: End of Study	On-Demand: Change From Baseline	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=57 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=14 Participants	Prophylaxis: Change From Baseline	Part 2 or Part 3: Week 26	Bleeding Cause: Unknown
Health Resource Use - Number of Hospitalizations Part 1 - Pharmacokinetics (N= 28, NA)	—	—	0.0 Hospitalizations Interval 0.0 to 0.0	NA Hospitalizations There were no participants from the On-Demand arm in Study Part 1	—	—	—
Health Resource Use - Number of Hospitalizations Part 2: Exposure Day 1 (N= 31, 14)	—	—	0.0 Hospitalizations Interval 0.0 to 0.0	0.0 Hospitalizations Interval 0.0 to 0.0	—	—	—
Health Resource Use - Number of Hospitalizations Part 2: Week 5 (N= 57, 14)	—	—	0.0 Hospitalizations Interval 0.0 to 1.0	0.0 Hospitalizations Interval 0.0 to 0.0	—	—	—
Health Resource Use - Number of Hospitalizations Part 2: Week 13 (N= 56, 12)	—	—	0.0 Hospitalizations Interval 0.0 to 1.0	0.0 Hospitalizations Interval 0.0 to 0.0	—	—	—
Health Resource Use - Number of Hospitalizations Part 2: Week 26 (N= 30, NA)	—	—	0.0 Hospitalizations Interval 0.0 to 0.0	NA Hospitalizations There were no participants from the On-Demand arm in Study Part 2 at Week 26	—	—	—
Health Resource Use - Number of Hospitalizations Part 3 (N= 25, NA)	—	—	0.0 Hospitalizations Interval 0.0 to 3.0	NA Hospitalizations There were no participants from the On-Demand arm in Study Part 3	—	—	—
Health Resource Use - Number of Hospitalizations Completion/Termination (N= 20, 9)	—	—	0.0 Hospitalizations Interval 0.0 to 1.0	0.0 Hospitalizations Interval 0.0 to 0.0	—	—	—
Health Resource Use - Number of Hospitalizations Unscheduled Study Visit (N= 1, NA)	—	—	0.0 Hospitalizations Interval 0.0 to 0.0	NA Hospitalizations There were no participants from the On-Demand arm with an unscheduled Study Visit	—	—	—

SECONDARY outcome

Timeframe: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

Population: Full Analysis Set

Outcome measures

Measure	On-Demand: End of Study	On-Demand: Change From Baseline	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=4 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study	Prophylaxis: Change From Baseline	Part 2 or Part 3: Week 26	Bleeding Cause: Unknown
Health Resource Use - Total Days of Hospital Stay Part 2: Week 5 (N= 1)	—	—	46.0 Days Interval 46.0 to 46.0	—	—	—	—
Health Resource Use - Total Days of Hospital Stay Part 2: Week 13 (N= 1)	—	—	23.0 Days Interval 23.0 to 23.0	—	—	—	—
Health Resource Use - Total Days of Hospital Stay Part 3 (N= 3)	—	—	2.0 Days Interval 1.0 to 16.0	—	—	—	—
Health Resource Use - Total Days of Hospital Stay Completion/Termination (N= 2)	—	—	5.5 Days Interval 2.0 to 9.0	—	—	—	—

SECONDARY outcome

Timeframe: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

Population: Full Analysis Set

Outcome measures

Measure	On-Demand: End of Study	On-Demand: Change From Baseline	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=57 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=14 Participants	Prophylaxis: Change From Baseline	Part 2 or Part 3: Week 26	Bleeding Cause: Unknown
Health Resource Use - Emergency Room Visits Part 1 - Pharmacokinetics (N= 28, NA)	—	—	0.0 Visits Interval 0.0 to 0.0	NA Visits There were no participants from the On-Demand arm in Study Part 1	—	—	—
Health Resource Use - Emergency Room Visits Part 2: Exposure Day 1 (N= 31, 14)	—	—	0.0 Visits Interval 0.0 to 10.0	0.0 Visits Interval 0.0 to 0.0	—	—	—
Health Resource Use - Emergency Room Visits Part 2: Week 5 (N= 57, 14)	—	—	0.0 Visits Interval 0.0 to 1.0	0.0 Visits Interval 0.0 to 0.0	—	—	—
Health Resource Use - Emergency Room Visits Part 2: Week 13 (N= 56, 12)	—	—	0.0 Visits Interval 0.0 to 1.0	0.0 Visits Interval 0.0 to 0.0	—	—	—
Health Resource Use - Emergency Room Visits Part 2: Week 26 (N= 30, NA)	—	—	0.0 Visits Interval 0.0 to 0.0	NA Visits There were no participants from the On-Demand arm in Study Part 2 at Week 26	—	—	—
Health Resource Use - Emergency Room Visits Part 3 (N= 25, NA)	—	—	0.0 Visits Interval 0.0 to 0.0	NA Visits There were no participants from the On-Demand arm in Study Part 3	—	—	—
Health Resource Use - Emergency Room Visits Completion/Termination (N= 20, 9)	—	—	0.0 Visits Interval 0.0 to 1.0	0.0 Visits Interval 0.0 to 0.0	—	—	—
Health Resource Use - Emergency Room Visits Unscheduled Study Visit (N= 1, NA)	—	—	0.0 Visits Interval 0.0 to 0.0	NA Visits There were no participants from the On-Demand arm with an unscheduled Study Visit	—	—	—

SECONDARY outcome

Timeframe: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

Population: Full Analysis Set

Outcome measures

Measure	On-Demand: End of Study	On-Demand: Change From Baseline	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=57 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=14 Participants	Prophylaxis: Change From Baseline	Part 2 or Part 3: Week 26	Bleeding Cause: Unknown
Health Resource Use - Unscheduled Doctor's Office Visits Part 1 - Pharmacokinetics (N= 28, NA)	—	—	0.0 Visits Interval 0.0 to 1.0	NA Visits There were no participants from the On-Demand arm in Study Part 1	—	—	—
Health Resource Use - Unscheduled Doctor's Office Visits Part 2: Exposure Day 1 (N= 31, 14)	—	—	0.0 Visits Interval 0.0 to 0.0	0.0 Visits Interval 0.0 to 0.0	—	—	—
Health Resource Use - Unscheduled Doctor's Office Visits Part 2: Week 5 (N= 57, 14)	—	—	0.0 Visits Interval 0.0 to 3.0	0.0 Visits Interval 0.0 to 0.0	—	—	—
Health Resource Use - Unscheduled Doctor's Office Visits Part 2: Week 13 (N= 56, 12)	—	—	0.0 Visits Interval 0.0 to 2.0	0.0 Visits Interval 0.0 to 0.0	—	—	—
Health Resource Use - Unscheduled Doctor's Office Visits Part 2: Week 26 (N= 30, NA)	—	—	0.0 Visits Interval 0.0 to 1.0	NA Visits There were no participants from the On-Demand arm in Study Part 2 at Week 26	—	—	—
Health Resource Use - Unscheduled Doctor's Office Visits Part 3 (N= 25, NA)	—	—	0.0 Visits Interval 0.0 to 1.0	NA Visits There were no participants from the On-Demand arm in Study Part 3	—	—	—
Health Resource Use - Unscheduled Doctor's Office Visits Completion/Termination (N= 20, 9)	—	—	0.0 Visits Interval 0.0 to 2.0	0.0 Visits Interval 0.0 to 1.0	—	—	—
Health Resource Use - Unscheduled Doctor's Office Visits Unscheduled Study Visit (N= 1, NA)	—	—	1.0 Visits Interval 1.0 to 1.0	NA Visits There were no participants from the On-Demand arm with an unscheduled Study Visit	—	—	—

SECONDARY outcome

Timeframe: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

Population: Full Analysis Set

Outcome measures

Measure	On-Demand: End of Study	On-Demand: Change From Baseline	Prophylaxis: Part 1 or Part 2, Exposure Day 1 (Baseline) n=57 Participants Prophylactic treatment of 50 IU/kg BAX326 twice weekly. The dose range is 40-60 IU/kg and may be increased up to 75 IU/kg, if required.	Prophylaxis: End of Study n=14 Participants	Prophylaxis: Change From Baseline	Part 2 or Part 3: Week 26	Bleeding Cause: Unknown
Health Resource Use - Days Lost From Work or School Unscheduled Study Visit (N= 1, NA)	—	—	0.0 Days Interval 0.0 to 0.0	NA Days There were no participants from the On-Demand arm with an unscheduled Study Visit	—	—	—
Health Resource Use - Days Lost From Work or School Part 1 - Pharmacokinetics (N= 28, NA)	—	—	0.0 Days Interval 0.0 to 10.0	NA Days There were no participants from the On-Demand arm in Study Part 1	—	—	—
Health Resource Use - Days Lost From Work or School Part 2: Exposure Day 1 (N= 31, 14)	—	—	0.0 Days Interval 0.0 to 2.0	0.0 Days Interval 0.0 to 0.0	—	—	—
Health Resource Use - Days Lost From Work or School Part 2: Week 5 (N= 57, 14)	—	—	0.0 Days Interval 0.0 to 8.0	0.0 Days Interval 0.0 to 4.0	—	—	—
Health Resource Use - Days Lost From Work or School Part 2: Week 13 (N= 56, 12)	—	—	0.0 Days Interval 0.0 to 7.0	0.0 Days Interval 0.0 to 0.0	—	—	—
Health Resource Use - Days Lost From Work or School Part 2: Week 26 (N= 30, NA)	—	—	0.0 Days Interval 0.0 to 5.0	NA Days There were no participants from the On-Demand arm in Study Part 2 at Week 26	—	—	—
Health Resource Use - Days Lost From Work or School Part 3 (N= 25, NA)	—	—	0.0 Days Interval 0.0 to 1.0	NA Days There were no participants from the On-Demand arm in Study Part 3	—	—	—
Health Resource Use - Days Lost From Work or School Completion/Termination (N= 20, 9)	—	—	0.0 Days Interval 0.0 to 24.0	0.0 Days Interval 0.0 to 0.0	—	—	—

Adverse Events

BAX326

Serious events: 4 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Measure	BAX326 n=73 participants at risk BAX326: -Study Part 1: Pharmacokinetic (PK) Crossover with BAX326 and BeneFIX •Study Part 2: Open-label evaluation of prophylaxis and on-demand BAX326 only •Study Part 3: Open-label repeat of PK evaluation (repeat Study Part 1) with BAX326 only and same study participants as Study Part 1
Gastrointestinal disorders Intestinal Obstruction	1.4% 1/73 • Number of events 1 • Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
Injury, poisoning and procedural complications Cervical Vertebral Fracture	1.4% 1/73 • Number of events 1 • Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
Injury, poisoning and procedural complications Traumatic Haematoma	1.4% 1/73 • Number of events 1 • Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
Investigations Hepatitis B Core Antibody Positive	1.4% 1/73 • Number of events 1 • Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
Nervous system disorders Convulsion	1.4% 1/73 • Number of events 1 • Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

Other adverse events

Measure	BAX326 n=73 participants at risk BAX326: -Study Part 1: Pharmacokinetic (PK) Crossover with BAX326 and BeneFIX •Study Part 2: Open-label evaluation of prophylaxis and on-demand BAX326 only •Study Part 3: Open-label repeat of PK evaluation (repeat Study Part 1) with BAX326 only and same study participants as Study Part 1
Infections and infestations Nasopharyngitis	8.2% 6/73 • Number of events 8 • Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
Investigations Immunology Test Abnormal	16.4% 12/73 • Number of events 12 • Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: ClinicalTransparency@shire.com

Results disclosure agreements

• Principal investigator is a sponsor employee Agreements may vary with individual PIs, but contain common elements. For this study, PIs are restricted from independently publishing results until the earlier of the primary multicenter publication or up to 3 years after study completion. Baxter requires a review of results communications (eg for confidential information) ≥60 days prior to submission/communication. Baxter may request additional delay of ≤180 days(e.g., for intellectual property protection). Prior authorization may be required.
• Publication restrictions are in place

Restriction type: OTHER