Trial Outcomes & Findings for A Trial Investigating Safety and Efficacy of Treatment With BAY94-9027 in Severe Hemophilia A (NCT NCT01580293)

NCT ID: NCT01580293

Last Updated: 2023-11-07

Results Overview

Annualized number of total bleeds was defined as the annualized sum of spontaneous bleeds and trauma bleeds. A participant who had the one-time increase in dose frequency was regarded as rescued. A rescue bleed was a bleed that occured after the dose frequency was increased. Rescue bleeds and periods were not considered for the annualized bleeding rate (ABR).

• Recruitment status: COMPLETED
• Study phase: PHASE2/PHASE3
• Target enrollment: 145 participants
• Primary outcome timeframe: On-demand: Weeks 0 -36 and Prophylaxis: Weeks 10 - 36 during Part A
• Results posted on: 2023-11-07

Participant Flow

The study was conducted in 3 parts: Part A (main study [36-week treatment period] and an optional extension [at least 100 total exposure days]) and Part B for major surgeries (up to 3 weeks).

Of 149 participants screened in Part A, 134 were treated, reasons for non-inclusion were screen failure, consent withdrawal, and non-adherence to protocol visit windows. Participants selected either on-demand or prophylaxis treatment at start of study according to their preference. Randomization to prophylaxis arms occurred after week 10.

Participant milestones

Measure	BAY94-9027 On-demand Treatment, Part A Participants received on-demand treatment with BAY94-9027 as an intravenous (IV) infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]). Participants entering extension either continued their on-demand treatment or switched to one of the prophylaxis regimens.	BAY94-9027 Prophylaxis Treatment, Part A All participants started BAY94-9027 IV infusion, with 2x/week at a dose of 25 IU/kg for 10 weeks. Thereafter, participants with less than 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. High bleeders continued 2x/week infusion (2x/week 'failed'). Participants qualified to be randomized but enrolled after randomized arms were filled, remained on 2x/week treatment (2x/week 'forced' group). Participants entering extension either continued their prophylaxis regimen or switched to one of the other prophylaxis regimens.	BAY949027 Treatment in Major Surgery, Part B Participants who underwent major surgery received study drug during their hospital stay up to 3 weeks post surgery. Participants were treated according to the type of procedure, using tailored doses (a maximum of 60 IU/kg/infusion) expected to maintain acceptable therapeutic level of FVIII activity.
Part A_Main Trial STARTED	20	114	0
Part A_Main Trial COMPLETED	18	108	0
Part A_Main Trial NOT COMPLETED	2	6	0
Part A_Extension STARTED	14	107	0
Part A_Extension COMPLETED	14	95	0
Part A_Extension NOT COMPLETED	0	12	0
Part B STARTED	0	0	19
Part B COMPLETED	0	0	17
Part B NOT COMPLETED	0	0	2

Reasons for withdrawal

Measure	BAY94-9027 On-demand Treatment, Part A Participants received on-demand treatment with BAY94-9027 as an intravenous (IV) infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]). Participants entering extension either continued their on-demand treatment or switched to one of the prophylaxis regimens.	BAY94-9027 Prophylaxis Treatment, Part A All participants started BAY94-9027 IV infusion, with 2x/week at a dose of 25 IU/kg for 10 weeks. Thereafter, participants with less than 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. High bleeders continued 2x/week infusion (2x/week 'failed'). Participants qualified to be randomized but enrolled after randomized arms were filled, remained on 2x/week treatment (2x/week 'forced' group). Participants entering extension either continued their prophylaxis regimen or switched to one of the other prophylaxis regimens.	BAY949027 Treatment in Major Surgery, Part B Participants who underwent major surgery received study drug during their hospital stay up to 3 weeks post surgery. Participants were treated according to the type of procedure, using tailored doses (a maximum of 60 IU/kg/infusion) expected to maintain acceptable therapeutic level of FVIII activity.
Part A_Main Trial Adverse Event	0	2	0
Part A_Main Trial Withdrawal by Subject	1	4	0
Part A_Main Trial Non-adherence to the protocol	1	0	0
Part A_Extension Adverse Event	0	2	0
Part A_Extension Withdrawal by Subject	0	3	0
Part A_Extension Lost to Follow-up	0	1	0
Part A_Extension Other Reason	0	1	0
Part A_Extension Completed Japan only	0	5	0
Part B Withdrawal by Subject	0	0	1
Part B Other reason	0	0	1

Baseline Characteristics

A Trial Investigating Safety and Efficacy of Treatment With BAY94-9027 in Severe Hemophilia A

Baseline characteristics by cohort

Measure	BAY94-9027 On-demand Treatment, Main Trial n=20 Participants Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]).	BAY94-9027 Prophylaxis Treatment, 2x/Week Dropped, Main Trial n=4 Participants 4 participants dropped out during week 0-10	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial n=13 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial n=11 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial n=43 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial n=43 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants \<2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.	BAY94-9027 Treatment in Major Surgery, Part B Only n=11 Participants Participants treated in Part B only were included. Participants treated in Part A and continued in Part B were excluded. Participants who underwent major surgery received study drug during their hospital stay and up until hospital discharge or 3 weeks post-surgery, whichever came first. Participants were treated according to the type of procedure, using tailored doses (a maximum of 60 IU/kg) expected to maintain acceptable therapeutic level of FVIII activity.	Total n=145 Participants Total of all reporting groups
Age, Continuous	44.8 years STANDARD_DEVIATION 13.5 • n=5 Participants	27.3 years STANDARD_DEVIATION 14.2 • n=7 Participants	31.4 years STANDARD_DEVIATION 11.6 • n=5 Participants	33.1 years STANDARD_DEVIATION 11.0 • n=4 Participants	33.7 years STANDARD_DEVIATION 13.0 • n=21 Participants	37.0 years STANDARD_DEVIATION 13.5 • n=8 Participants	37.9 years STANDARD_DEVIATION 13.7 • n=8 Participants	36.1 years STANDARD_DEVIATION 13.5 • n=24 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	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	4 Participants n=7 Participants	13 Participants n=5 Participants	11 Participants n=4 Participants	43 Participants n=21 Participants	43 Participants n=8 Participants	11 Participants n=8 Participants	145 Participants n=24 Participants

PRIMARY outcome

Timeframe: On-demand: Weeks 0 -36 and Prophylaxis: Weeks 10 - 36 during Part A

Population: Intent to treat (ITT) population part A week 10-36, 4 participants dropped out during week 0-10.

Annualized number of total bleeds was defined as the annualized sum of spontaneous bleeds and trauma bleeds. A participant who had the one-time increase in dose frequency was regarded as rescued. A rescue bleed was a bleed that occured after the dose frequency was increased. Rescue bleeds and periods were not considered for the annualized bleeding rate (ABR).

Outcome measures

Measure	BAY94-9027 On-demand Treatment, Main Trial n=20 Participants Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]).	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial n=13 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial n=11 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial n=43 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial n=43 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants \<2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.	BAY94-9027 Prophylaxis Treatment Total, Main Trial n=110 Participants All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Annualized Number of Total Bleeds in On-demand Treatment Arm (Weeks 0 -36) and in Each Prophylaxis Arm (Weeks 10 - 36, Excluding Rescue Bleeds) - Part A, Main Trial	23.42 bleeds Interval 17.84 to 37.25	4.11 bleeds Interval 2.01 to 10.56	1.93 bleeds Interval 0.0 to 5.24	1.93 bleeds Interval 0.0 to 4.23	3.85 bleeds Interval 0.0 to 6.47	2.09 bleeds Interval 0.0 to 6.05

SECONDARY outcome

Timeframe: On-demand: Weeks 0 -36 and Prophylaxis: Weeks 10 - 36 during Part A

Population: ITT population part A week 10-36, 4 participants dropped out during week 0-10.

A participant who had the one-time increase in dose frequency was regarded as rescued. A rescue bleed was a bleed that occured after the dose frequency was increased. Rescue bleeds and periods were not considered for the ABR.

Outcome measures

Measure	BAY94-9027 On-demand Treatment, Main Trial n=20 Participants Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]).	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial n=13 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial n=11 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial n=43 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial n=43 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants \<2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.	BAY94-9027 Prophylaxis Treatment Total, Main Trial n=110 Participants All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Annualized Number of Joint Bleeds, Trauma, Spontaneous Bleeds in On-demand Treatment Arm (Weeks 0 -36) and in Each Prophylaxis Arm (Weeks 10 - 36, Excluding Rescue Bleeds) - Part A Joint Bleeds	16.34 bleeds Interval 11.61 to 30.3	4.01 bleeds Interval 1.98 to 8.03	1.93 bleeds Interval 0.0 to 5.24	1.86 bleeds Interval 0.0 to 3.99	1.92 bleeds Interval 0.0 to 6.26	1.93 bleeds Interval 0.0 to 5.24
Annualized Number of Joint Bleeds, Trauma, Spontaneous Bleeds in On-demand Treatment Arm (Weeks 0 -36) and in Each Prophylaxis Arm (Weeks 10 - 36, Excluding Rescue Bleeds) - Part A Trauma Bleeds	9.09 bleeds Interval 3.08 to 15.53	1.98 bleeds Interval 0.0 to 5.8	0.00 bleeds Interval 0.0 to 1.93	0.00 bleeds Interval 0.0 to 2.09	0.00 bleeds Interval 0.0 to 0.0	0.00 bleeds Interval 0.0 to 1.98
Annualized Number of Joint Bleeds, Trauma, Spontaneous Bleeds in On-demand Treatment Arm (Weeks 0 -36) and in Each Prophylaxis Arm (Weeks 10 - 36, Excluding Rescue Bleeds) - Part A Spontaneous Bleeds	14.29 bleeds Interval 7.26 to 22.71	3.87 bleeds Interval 0.0 to 4.11	0.00 bleeds Interval 0.0 to 1.93	0.00 bleeds Interval 0.0 to 3.99	1.93 bleeds Interval 0.0 to 6.33	0.00 bleeds Interval 0.0 to 4.17

SECONDARY outcome

Timeframe: at least 100 total exposure days acquired, median time 3.9 years up to 7 years maximum

Population: ITT extension population. Participants in each regimen stayed on this regimen without switch. Participants who switched regimen were analyzed in the variable frequency arm.

Annualized number of total bleeds was defined as the annualized sum of spontaneous bleeds and trauma bleeds.

Outcome measures

Measure	BAY94-9027 On-demand Treatment, Main Trial n=14 Participants Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]).	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial n=23 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial n=33 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial n=23 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial n=28 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants \<2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.	BAY94-9027 Prophylaxis Treatment Total, Main Trial All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Annualized Number of Total Bleeds in On-demand Treatment Arm and in Each Prophylaxis Arm, Part A, Extension	34.09 bleeds Interval 20.33 to 36.63	1.57 bleeds Interval 0.79 to 3.61	1.17 bleeds Interval 0.0 to 4.57	0.65 bleeds Interval 0.0 to 1.68	3.10 bleeds Interval 1.13 to 5.86	—

SECONDARY outcome

Timeframe: Weeks 0 to 36 during Part A

Population: Part A safety population (N=134) included all participants who received at least 1 dose of study drug during Part A of the study.

FVIII inhibitor testing was done according to the Nijmegen modified Bethesda assay. A positive inhibitor test was defined with a threshold of ≥0.6 Bethesda unit (BU) at the central laboratory.

Outcome measures

Measure	BAY94-9027 On-demand Treatment, Main Trial n=20 Participants Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]).	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial n=114 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants \<2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.	BAY94-9027 Prophylaxis Treatment Total, Main Trial All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Number of Participants Developed Human Coagulation Factor VIII (FVIII) Inhibitor - Part A	0 Participants	0 Participants	—	—	—	—

SECONDARY outcome

Timeframe: Weeks 0 to 36

Population: Part A ITT population, analysis population includes participants who presented \>=1 bleeding event.

Number of bleeds requiring 1, 2 or >= 3 infusions to control the bleeding

Outcome measures

Measure	BAY94-9027 On-demand Treatment, Main Trial n=386 bleeds Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]).	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial n=316 bleeds All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants \<2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.	BAY94-9027 Prophylaxis Treatment Total, Main Trial All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Number of Bleeds Requiring 1, 2 or >= 3 Infusions to Control the Bleed - Part A 1 infusion	307 bleeds	262 bleeds	—	—	—	—
Number of Bleeds Requiring 1, 2 or >= 3 Infusions to Control the Bleed - Part A 2 infusions	45 bleeds	22 bleeds	—	—	—	—
Number of Bleeds Requiring 1, 2 or >= 3 Infusions to Control the Bleed - Part A Greater than or equal to (>=) 3 infusions	34 bleeds	32 bleeds	—	—	—	—

SECONDARY outcome

Timeframe: Weeks 0 -36

Population: Analysis population includes participants who presented \>=1 bleeding event.

Bleed locations were categorised as joint, muscle, skin/mucosa, internal, others and missing.

Outcome measures

Measure	BAY94-9027 On-demand Treatment, Main Trial n=386 bleeds Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]).	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial n=316 bleeds All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants \<2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.	BAY94-9027 Prophylaxis Treatment Total, Main Trial All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Number of Bleeds According to Locations - Part A Missing	0 bleeds	0 bleeds	—	—	—	—
Number of Bleeds According to Locations - Part A Joint	303 bleeds	235 bleeds	—	—	—	—
Number of Bleeds According to Locations - Part A Muscle	54 bleeds	59 bleeds	—	—	—	—
Number of Bleeds According to Locations - Part A Skin/Mucosa	12 bleeds	12 bleeds	—	—	—	—
Number of Bleeds According to Locations - Part A Internal	7 bleeds	7 bleeds	—	—	—	—
Number of Bleeds According to Locations - Part A Other	26 bleeds	16 bleeds	—	—	—	—

SECONDARY outcome

Timeframe: Weeks 0 to 36

Population: Analysis population includes participants who presented \>=1 bleeding event.

Outcome measures

Measure	BAY94-9027 On-demand Treatment, Main Trial n=386 bleeds Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]).	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial n=316 bleeds All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants \<2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.	BAY94-9027 Prophylaxis Treatment Total, Main Trial All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Number of Bleeds Over Time Since Previous Prophylaxis Infusion - Part A <1 day	4 bleeds	21 bleeds	—	—	—	—
Number of Bleeds Over Time Since Previous Prophylaxis Infusion - Part A >=1 to <2 days	19 bleeds	62 bleeds	—	—	—	—
Number of Bleeds Over Time Since Previous Prophylaxis Infusion - Part A >=2 to <3 days	30 bleeds	82 bleeds	—	—	—	—
Number of Bleeds Over Time Since Previous Prophylaxis Infusion - Part A >=3 to <4 days	30 bleeds	69 bleeds	—	—	—	—
Number of Bleeds Over Time Since Previous Prophylaxis Infusion - Part A >=4 to <5 days	38 bleeds	32 bleeds	—	—	—	—
Number of Bleeds Over Time Since Previous Prophylaxis Infusion - Part A >=5 to <6 days	42 bleeds	36 bleeds	—	—	—	—
Number of Bleeds Over Time Since Previous Prophylaxis Infusion - Part A >=6 to <7 days	31 bleeds	11 bleeds	—	—	—	—
Number of Bleeds Over Time Since Previous Prophylaxis Infusion - Part A >=7 days	192 bleeds	3 bleeds	—	—	—	—

SECONDARY outcome

Timeframe: Weeks 0 to 36 during Part A

Population: Analysis population includes participants who presented \>=1 bleeding event.

Response to treatment was assessed by participant as excellent, good, moderate, poor or missing during Part A of the study.

Outcome measures

Measure	BAY94-9027 On-demand Treatment, Main Trial n=386 bleeds Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]).	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial n=316 bleeds All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants \<2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.	BAY94-9027 Prophylaxis Treatment Total, Main Trial All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Number of Bleeds According to Participant's Assessment of Response to Treatment - Part A Excellent or Good	252 bleeds	256 bleeds	—	—	—	—
Number of Bleeds According to Participant's Assessment of Response to Treatment - Part A Excellent	81 bleeds	107 bleeds	—	—	—	—
Number of Bleeds According to Participant's Assessment of Response to Treatment - Part A Good	171 bleeds	149 bleeds	—	—	—	—
Number of Bleeds According to Participant's Assessment of Response to Treatment - Part A Moderate	115 bleeds	47 bleeds	—	—	—	—
Number of Bleeds According to Participant's Assessment of Response to Treatment - Part A Poor	16 bleeds	7 bleeds	—	—	—	—
Number of Bleeds According to Participant's Assessment of Response to Treatment - Part A Missing	3 bleeds	6 bleeds	—	—	—	—

SECONDARY outcome

Timeframe: On-demand: Weeks 0 -36 and Prophylaxis: Weeks 10 - 36 during Part A

Population: ITT population part A week 10-36, 4 participants dropped out during week 0-10.

For prophylaxis patients, the dose is related to all infusions.

Outcome measures

Measure	BAY94-9027 On-demand Treatment, Main Trial n=20 Participants Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]).	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial n=13 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial n=11 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial n=43 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial n=43 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants \<2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.	BAY94-9027 Prophylaxis Treatment Total, Main Trial n=110 Participants All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Recombinant Human Factor VIII (rFVIII) Usage Expressed as Total Dose Per Kilogram Per Year - Part A	1518.5 IU/kg/year Interval 390.0 to 3655.0	4421.4 IU/kg/year Interval 3759.0 to 5978.0	3314.4 IU/kg/year Interval 2651.0 to 4062.0	3482.9 IU/kg/year Interval 2936.0 to 6774.0	3338.7 IU/kg/year Interval 2764.0 to 5789.0	3421.0 IU/kg/year Interval 2651.0 to 6774.0

SECONDARY outcome

Timeframe: On-demand: Weeks 0 -36 and Prophylaxis: Weeks 10 - 36 during Part A

Population: ITT population part A week 10-36, 4 participants dropped out during week 0-10.

For prophylaxis patients, the dose per infusion related to prophylaxis infusion.

Outcome measures

Measure	BAY94-9027 On-demand Treatment, Main Trial n=20 Participants Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]).	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial n=13 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial n=11 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial n=43 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial n=43 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants \<2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.	BAY94-9027 Prophylaxis Treatment Total, Main Trial n=110 Participants All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Recombinant Human Factor VIII (rFVIII) Usage Expressed as Dose Per Kilogram Per Infusion - Part A	32.8 IU/kg/infusion Interval 23.0 to 58.0	39.2 IU/kg/infusion Interval 33.0 to 42.0	30.6 IU/kg/infusion Interval 29.0 to 41.0	45.3 IU/kg/infusion Interval 39.0 to 58.0	59.0 IU/kg/infusion Interval 51.0 to 64.0	46.9 IU/kg/infusion Interval 29.0 to 64.0

SECONDARY outcome

Timeframe: Weeks 10 to 36 during Part A

Population: ITT population part A week 10-36, 4 participants dropped out during week 0-10.

Outcome measures

Measure	BAY94-9027 On-demand Treatment, Main Trial n=13 Participants Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]).	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial n=11 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial n=43 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial n=43 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial n=110 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants \<2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.	BAY94-9027 Prophylaxis Treatment Total, Main Trial All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Number of Participants Requiring an Increase in Dose Frequency, or Dose Increase, During Weeks 10 to 36 - Part A Dose increased	2 Participants	0 Participants	7 Participants	0 Participants	9 Participants	—
Number of Participants Requiring an Increase in Dose Frequency, or Dose Increase, During Weeks 10 to 36 - Part A Dose frequency increased	0 Participants	0 Participants	0 Participants	11 Participants	11 Participants	—

SECONDARY outcome

Timeframe: Day of surgery

Population: 17 participants were included in the Part B ITT population.

Major surgery was defined as any surgical or invasive procedure (elective or emergent) in which the overall bleeding risk was excessive, required a general anesthetic in an individual without a bleeding disorder, penetrated or exposed a major body cavity, resulted in substantial impairment of physical or physiological functions, or required special anatomic knowledge or manipulative skill. Adequacy of hemostasis was assessed as excellent, good, moderate or poor, by the surgeon or interventionalist during Part B of the study.

Outcome measures

Measure	BAY94-9027 On-demand Treatment, Main Trial n=20 surgeries Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]).	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants \<2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.	BAY94-9027 Prophylaxis Treatment Total, Main Trial All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Number of Surgeries According to Physician's Assessment of Adequacy of Hemostasis in Major Surgery - Part B Good	13 surgeries	—	—	—	—	—
Number of Surgeries According to Physician's Assessment of Adequacy of Hemostasis in Major Surgery - Part B Excellent	7 surgeries	—	—	—	—	—
Number of Surgeries According to Physician's Assessment of Adequacy of Hemostasis in Major Surgery - Part B Moderate	0 surgeries	—	—	—	—	—
Number of Surgeries According to Physician's Assessment of Adequacy of Hemostasis in Major Surgery - Part B Poor	0 surgeries	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to 3 weeks post-surgery during Part B

Population: Part B ITT population

Major surgery was defined as any surgical or invasive procedure (elective or emergent) in which the overall bleeding risk was excessive, required a general anesthetic in an individual without a bleeding disorder, penetrated or exposed a major body cavity, resulted in substantial impairment of physical or physiological functions, or required special anatomic knowledge or manipulative skill. Total dose per kilogram per Infusion was expressed in international units per kilogram per infusion (IU/kg/infusion).

Outcome measures

Measure	BAY94-9027 On-demand Treatment, Main Trial n=20 surgeries Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]).	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants \<2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.	BAY94-9027 Prophylaxis Treatment Total, Main Trial All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Recombinant Human Factor VIII (rFVIII) Usage Expressed as Dose Per Kilogram Per Infusion for Major Surgery - Part B	33.7 IU/kg/infusion Interval 22.0 to 51.0	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to 3 weeks post-surgery during Part B

Population: Part B ITT population

Major surgery was defined as any surgical or invasive procedure (elective or emergent) in which the overall bleeding risk was excessive, required a general anesthetic in an individual without a bleeding disorder, penetrated or exposed a major body cavity, resulted in substantial impairment of physical or physiological functions, or required special anatomic knowledge or manipulative skill.rFVIII usage expressed as number of infusions and IU/kg per year, as well as IU/kg per event (surgery) was assessed by investigator.

Outcome measures

Measure	BAY94-9027 On-demand Treatment, Main Trial n=20 surgeries Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]).	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants \<2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.	BAY94-9027 Prophylaxis Treatment Total, Main Trial All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Recombinant Human Factor VIII (rFVIII) Usage Expressed as Number of Infusions for Major Surgery - Part B	8.0 infusions Interval 3.0 to 39.0	—	—	—	—	—

SECONDARY outcome

Timeframe: Weeks 0 and 36: pre-infusion (0 hours), post-infusion 15, 30 minutes, 1, 3, 6, 8, 24, 48, 72, 96 hours

Population: Pharmacokinetic Analysis Set (PKS) with participants evaluable for this outcome, PKS included all participants with a valid profile of BAY94-9027 during Part A of the study.

Cmax: Maximum observed drug concentration following an infusion of 60 IU/kg

Outcome measures

Measure	BAY94-9027 On-demand Treatment, Main Trial n=22 Participants Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]).	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial n=15 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants \<2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.	BAY94-9027 Prophylaxis Treatment Total, Main Trial All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Maximum Drug Plasma Concentration (Cmax) Following Single and Multiple Doses of BAY94-9027, Chromogenic Assay - Part A	162.8 IU/dL Geometric Coefficient of Variation 14.74	177.1 IU/dL Geometric Coefficient of Variation 20.98	—	—	—	—

SECONDARY outcome

Timeframe: Weeks 0 and 36: pre-infusion (0 hours), post-infusion 15, 30 minutes, 1, 3, 6, 8, 24, 48, 72, 96 hours

Population: PKS with participants evaluable for this outcome

AUC: The total area under the plasma concentration versus time curve following an infusion of 60 IU/kg .

Outcome measures

Measure	BAY94-9027 On-demand Treatment, Main Trial n=22 Participants Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]).	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial n=15 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants \<2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.	BAY94-9027 Prophylaxis Treatment Total, Main Trial All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC) Following Single and Multiple Doses of BAY94-9027, Chromogenic Assay - Part A	3707.5 h*IU/dL Geometric Coefficient of Variation 33.77	4130.8 h*IU/dL Geometric Coefficient of Variation 28.8	—	—	—	—

SECONDARY outcome

Timeframe: Weeks 0 and 36: pre-infusion (0 hours), post-infusion 15, 30 minutes, 1, 3, 6, 8, 24, 48, 72, 96 hours

Population: PKS with participants evaluable for this outcome

t1/2: Terminal half-life is the time the plasma concentration during terminal phase is halved following an infusion of 60 IU/kg .

Outcome measures

Measure	BAY94-9027 On-demand Treatment, Main Trial n=22 Participants Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]).	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial n=15 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants \<2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.	BAY94-9027 Prophylaxis Treatment Total, Main Trial All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Terminal Elimination Half Life (t1/2) Following Single and Multiple Doses of BAY94-9027, Chromogenic Assay - Part A	17.1 Hours Geometric Coefficient of Variation 27.05	19.6 Hours Geometric Coefficient of Variation 38.48	—	—	—	—

SECONDARY outcome

Timeframe: Weeks 0 to 36 during Part A

Population: Part A ITT population

Recovery was calculated by the following formula: Recovery = (post-infusion FVIII activity - pre-infusion FVIII activity ) * weight / dose (in IU). Recovery is the increase of FVIII activity after the injection normalized by dose: IU/dl per IU/kg = kg/dL

Outcome measures

Measure	BAY94-9027 On-demand Treatment, Main Trial n=20 Participants Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]).	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial n=112 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants \<2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.	BAY94-9027 Prophylaxis Treatment Total, Main Trial All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Overall Human Coagulation Factor VIII (FVIII) Recovery Value by Chromogenic Assay - Part A	2.67 Kilogram per deciliter Standard Deviation 0.54	2.68 Kilogram per deciliter Standard Deviation 0.55	—	—	—	—

SECONDARY outcome

Timeframe: Week 0 (baseline) and Week 36 during Part A

Population: Part A ITT population with participants evaluable for this outcome

Quality of life (QoL) was measured by the Haemo-QoL-A overall score, which ranged from 0 (the worst condition) to 100 (the best condition).

Outcome measures

Measure	BAY94-9027 On-demand Treatment, Main Trial n=19 Participants Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]).	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial n=97 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants \<2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.	BAY94-9027 Prophylaxis Treatment Total, Main Trial All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Change From Baseline in Quality of Life by Hemophilia Specific Quality of Life Instrument or Questionnaire for Adults (Haemo-QoL-A) Overall Score at Week 36 - Part A	-0.14 scores on a scale Standard Deviation 9.70	2.59 scores on a scale Standard Deviation 7.98	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 0 (baseline) and Week 36 during Part A

Population: Analysis population includes participants evaluable in each category for this outcome.

Brief Pain Inventory (BPI) - Short Form (BPI-SF) was a 15-item, self-administered, validated tool developed to assess pain used in the study for patient reported outcomes. Scores ranged from 0 to 10 and a higher score indicates a higher level of pain/interference.

Outcome measures

Measure	BAY94-9027 On-demand Treatment, Main Trial n=20 Participants Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]).	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial n=112 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants \<2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.	BAY94-9027 Prophylaxis Treatment Total, Main Trial All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Change From Baseline in Overall Pain Severity and Interference Due to Pain at Week 36 - Part A Pain severity subscale	-0.8 scores on a scale Standard Deviation 1.8	0.1 scores on a scale Standard Deviation 1.39	—	—	—	—
Change From Baseline in Overall Pain Severity and Interference Due to Pain at Week 36 - Part A Interference subscale	-0.99 scores on a scale Standard Deviation 2.54	-0.06 scores on a scale Standard Deviation 1.39	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 0 (baseline) and Week 36 during Part A

Population: Analysis population includes participants evaluable in each category for this outcome.

The WPAI is a validated instrument to assess the effect of hemophilia on ability to work, attend classes, and perform regular daily activities in participants aged 12 and above. The WPAI also contained classroom impairment questions (CIQ). The questionnaire was self-administered and comprised of nine questions that elicited information on work, classroom, and daily activity impairment during the previous seven days. WPAI outcomes that are overall work and activity impairment, transformed to impairment percentages (range from 0 to 100), with higher numbers indicating greater impairment and less productivity.

Outcome measures

Measure	BAY94-9027 On-demand Treatment, Main Trial n=20 Participants Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]).	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial n=112 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants \<2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.	BAY94-9027 Prophylaxis Treatment Total, Main Trial All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Change From Baseline in Work Productivity and Activity Impairment (WPAI) Questionnaire at Week 36 - Part A Activity impairment	4.74 scores on a scale Standard Deviation 24.12	-7.13 scores on a scale Standard Deviation 20.00	—	—	—	—
Change From Baseline in Work Productivity and Activity Impairment (WPAI) Questionnaire at Week 36 - Part A Overall work impairment	4.44 scores on a scale Standard Deviation 21.94	-1.22 scores on a scale Standard Deviation 21.94	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: On-demand: Weeks 0 -36 and Prophylaxis: Weeks 10 - 36 during Part A

Population: ITT population part A week 10-36, 4 participants dropped out during week 0-10.

For prophylaxis patients, the dose is related to all infusions.

Outcome measures

Measure	BAY94-9027 On-demand Treatment, Main Trial n=20 Participants Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]).	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial n=13 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial n=11 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial n=43 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial n=43 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants \<2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.	BAY94-9027 Prophylaxis Treatment Total, Main Trial n=110 Participants All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Recombinant Human Factor VIII (rFVIII) Usage Expressed as Number of Infusions- Part A	29 infusions Interval 9.0 to 76.0	56.0 infusions Interval 52.0 to 71.0	55.0 infusions Interval 47.0 to 59.0	38.0 infusions Interval 3.0 to 58.0	27.0 infusions Interval 5.0 to 63.0	37.5 infusions Interval 3.0 to 71.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 10 - 36 during Part A

Population: ITT population part A week 10-36, 4 participants dropped out during week 0-10.

For prophylaxis patients, the dose per kilogram is related to prophylaxis infusions.

Outcome measures

Measure	BAY94-9027 On-demand Treatment, Main Trial n=13 Participants Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]).	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial n=11 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial n=43 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial n=43 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial n=110 Participants All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants \<2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.	BAY94-9027 Prophylaxis Treatment Total, Main Trial All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Recombinant Human Factor VIII (rFVIII) Usage Expressed as Dose Per Kilogram With Prophylaxis Treatment - Part A	1986.9 IU/kg Interval 1733.0 to 2236.0	1669.1 IU/kg Interval 1430.0 to 1947.0	1704.3 IU/kg Interval 139.0 to 2049.0	1530.2 IU/kg Interval 122.0 to 1788.0	1644.9 IU/kg Interval 122.0 to 2236.0	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 0 to 36 during Part A

Population: Part A ITT population

Minor surgery was defined as any surgical procedure that did not meet the definition of major, and included simple dental extractions, incision and drainage of abscesses, or simple excisions.

Outcome measures

Measure	BAY94-9027 On-demand Treatment, Main Trial n=17 minor surgeries Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]).	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants \<2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.	BAY94-9027 Prophylaxis Treatment Total, Main Trial All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Number of Minor Surgeries According to Physician's Assessment of Adequacy of Hemostasis - Part A Excellent	9 minor surgeries	—	—	—	—	—
Number of Minor Surgeries According to Physician's Assessment of Adequacy of Hemostasis - Part A Good	6 minor surgeries	—	—	—	—	—
Number of Minor Surgeries According to Physician's Assessment of Adequacy of Hemostasis - Part A Missing	2 minor surgeries	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 3 weeks post-surgery during Part B

Population: Part B ITT population

Response to treatment during surgery was assessed by investigator/surgeon as excellent, good, moderate, poor or missing during Part B of the study.

Outcome measures

Measure	BAY94-9027 On-demand Treatment, Main Trial n=17 surgeries Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]).	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants \<2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.	BAY94-9027 Prophylaxis Treatment Total, Main Trial All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Number of Surgeries According to Physician's Assessment of Response to Hemostasis, Post-surgery - Part B Main Trial Excellent	8 surgeries	—	—	—	—	—
Number of Surgeries According to Physician's Assessment of Response to Hemostasis, Post-surgery - Part B Main Trial Good	5 surgeries	—	—	—	—	—
Number of Surgeries According to Physician's Assessment of Response to Hemostasis, Post-surgery - Part B Main Trial Moderate	3 surgeries	—	—	—	—	—
Number of Surgeries According to Physician's Assessment of Response to Hemostasis, Post-surgery - Part B Main Trial Missing	1 surgeries	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 3 weeks post-surgery during Part B

Population: Part B Safety population (N=17) included all participants who received at least 1 dose of study drug during Part B of the study.

Hematocrit is defined as the volume percentage (%) of red blood cells in blood.

Outcome measures

Measure	BAY94-9027 On-demand Treatment, Main Trial n=17 Participants Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]).	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants \<2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.	BAY94-9027 Prophylaxis Treatment Total, Main Trial All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Number of Participants With Change/Drop in Hemoglobin/Hematocrit Laboratory Assessments - Part B Hematocrit	6 Participants	—	—	—	—	—
Number of Participants With Change/Drop in Hemoglobin/Hematocrit Laboratory Assessments - Part B Hemoglobin	2 Participants	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: day of surgery

Population: Part B ITT population with participants treated for major surgery

Major surgery was defined as any surgical or invasive procedure (elective or emergent) in which the overall bleeding risk was excessive, required a general anesthetic in an individual without a bleeding disorder, penetrated or exposed a major body cavity, resulted in substantial impairment of physical or physiological functions, or required special anatomic knowledge or manipulative skill.

Outcome measures

Measure	BAY94-9027 On-demand Treatment, Main Trial n=20 surgeries Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]).	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants \<2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.	BAY94-9027 Prophylaxis Treatment Total, Main Trial All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Maximum Blood Loss During Major Surgery - Part B	1000 milliliter	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 3 weeks post-surgery during Part B

Population: Part B ITT population with participants treated for major surgery

Major surgery was defined as any surgical or invasive procedure (elective or emergent) in which the overall bleeding risk was excessive, required a general anesthetic in an individual without a bleeding disorder, penetrated or exposed a major body cavity, resulted in substantial impairment of physical or physiological functions, or required special anatomic knowledge or manipulative skill.

Outcome measures

Measure	BAY94-9027 On-demand Treatment, Main Trial n=17 Participants Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]).	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants \<2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.	BAY94-9027 Prophylaxis Treatment Total, Main Trial All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Number of Participants Who Took Anti-fibrinolytic Medications During Major Surgery - Part B	8 Participants	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 3 weeks post-surgery during Part B

Population: Part B ITT population who had blood transfusions during major surgery

Major surgery was defined as any surgical or invasive procedure (elective or emergent) in which the overall bleeding risk was excessive, required a general anesthetic in an individual without a bleeding disorder, penetrated or exposed a major body cavity, resulted in substantial impairment of physical or physiological functions, or required special anatomic knowledge or manipulative skill.

Outcome measures

Measure	BAY94-9027 On-demand Treatment, Main Trial n=5 surgeries Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram \[IU/kg\]).	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with \< 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants \<2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.	BAY94-9027 Prophylaxis Treatment Total, Main Trial All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.
Volume of Blood Transfused in Major Surgery - Part B	865 milliliter Interval 600.0 to 1380.0	—	—	—	—	—

Adverse Events

BAY94-9027 Treatment, Part A, Main Trial

Serious events: 13 serious events

Other events: 67 other events

Deaths: 0 deaths

BAY94-9027 Treatment, Part A, Extension

Serious events: 36 serious events

Other events: 74 other events

Deaths: 0 deaths

BAY94-9027 Treatment in Major Surgery, Part B

Serious events: 2 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Measure	BAY94-9027 Treatment, Part A, Main Trial n=134 participants at risk Subjects entering Part A main trial were treated with BAY 94-9027 for either on-demand or prophylactic treatment.	BAY94-9027 Treatment, Part A, Extension n=121 participants at risk Subjects in Part A extension either continued their regimen from main trial or switched to one of the other regimens at any time.	BAY94-9027 Treatment in Major Surgery, Part B n=22 participants at risk Subjects, either Part B subjects only or subjects from Part A/Part A Extension, who underwent major surgery received study drug during their hospital stay up to 3 weeks post-surgery. Subjects were treated according to the type of procedure, using tailored doses (a maximum of 60 IU/kg/infusion) expected to maintain acceptable therapeutic level of FVIII activity.
Hepatobiliary disorders Hepatic cirrhosis	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Immune system disorders Drug hypersensitivity	0.75% 1/134 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/121 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Infections and infestations Anal abscess	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 3 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Infections and infestations Arthritis bacterial	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Infections and infestations Cellulitis	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Blood and lymphatic system disorders Anaemia	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Cardiac disorders Angina unstable	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Eye disorders Macular fibrosis	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Gastrointestinal disorders Anal fistula	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 2 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Gastrointestinal disorders Enterocolitis	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Gastrointestinal disorders Inguinal hernia	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	1.7% 2/121 • Number of events 3 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Gastrointestinal disorders Mouth haemorrhage	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Gastrointestinal disorders Pancreatitis acute	0.75% 1/134 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/121 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Gastrointestinal disorders Retroperitoneal haematoma	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Gastrointestinal disorders Tooth impacted	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	1.7% 2/121 • Number of events 2 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Hepatobiliary disorders Bile duct stone	0.75% 1/134 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/121 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Infections and infestations Device related infection	0.75% 1/134 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/121 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Infections and infestations Gastroenteritis	0.75% 1/134 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/121 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Infections and infestations Medical device site joint infection	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Infections and infestations Nasal vestibulitis	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Infections and infestations Pneumonia	0.75% 1/134 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/121 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Injury, poisoning and procedural complications Alcohol poisoning	0.75% 1/134 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/121 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Injury, poisoning and procedural complications Contusion	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Injury, poisoning and procedural complications Fall	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Injury, poisoning and procedural complications Fibula fracture	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Injury, poisoning and procedural complications Hand fracture	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Injury, poisoning and procedural complications Head injury	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	1.7% 2/121 • Number of events 2 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Injury, poisoning and procedural complications Injury	0.75% 1/134 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/121 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Injury, poisoning and procedural complications Ligament rupture	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Injury, poisoning and procedural complications Overdose	0.75% 1/134 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/121 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Injury, poisoning and procedural complications Periprosthetic fracture	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Injury, poisoning and procedural complications Tendon rupture	0.75% 1/134 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/121 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Investigations Anti factor VIII antibody positive	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/121 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	9.1% 2/22 • Number of events 2 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Investigations Colonoscopy	0.75% 1/134 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/121 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Investigations Liver function test increased	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 2 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Musculoskeletal and connective tissue disorders Arthropathy	0.75% 1/134 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 2 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	1.7% 2/121 • Number of events 3 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Musculoskeletal and connective tissue disorders Chondrocalcinosis pyrophosphate	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Musculoskeletal and connective tissue disorders Haemarthrosis	0.75% 1/134 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Musculoskeletal and connective tissue disorders Haemophilic arthropathy	0.75% 1/134 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	3.3% 4/121 • Number of events 5 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Musculoskeletal and connective tissue disorders Synovitis	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Nervous system disorders Epilepsy	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Product Issues Device malfunction	0.75% 1/134 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/121 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Psychiatric disorders Depression	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Renal and urinary disorders Hydronephrosis	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Renal and urinary disorders Nephrolithiasis	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Renal and urinary disorders Renal colic	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Renal and urinary disorders Ureterolithiasis	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Skin and subcutaneous tissue disorders Dermatitis exfoliative generalised	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Surgical and medical procedures Joint arthroplasty	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Surgical and medical procedures Knee arthroplasty	0.75% 1/134 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/121 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Surgical and medical procedures Renal stone removal	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 2 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Surgical and medical procedures Ureteral stent insertion	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Vascular disorders Haematoma	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	1.7% 2/121 • Number of events 2 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	4.5% 1/22 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.

Other adverse events

Measure	BAY94-9027 Treatment, Part A, Main Trial n=134 participants at risk Subjects entering Part A main trial were treated with BAY 94-9027 for either on-demand or prophylactic treatment.	BAY94-9027 Treatment, Part A, Extension n=121 participants at risk Subjects in Part A extension either continued their regimen from main trial or switched to one of the other regimens at any time.	BAY94-9027 Treatment in Major Surgery, Part B n=22 participants at risk Subjects, either Part B subjects only or subjects from Part A/Part A Extension, who underwent major surgery received study drug during their hospital stay up to 3 weeks post-surgery. Subjects were treated according to the type of procedure, using tailored doses (a maximum of 60 IU/kg/infusion) expected to maintain acceptable therapeutic level of FVIII activity.
Gastrointestinal disorders Nausea	3.7% 5/134 • Number of events 6 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	4.1% 5/121 • Number of events 7 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	9.1% 2/22 • Number of events 2 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
General disorders Pyrexia	0.75% 1/134 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	8.3% 10/121 • Number of events 13 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	13.6% 3/22 • Number of events 3 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Infections and infestations Influenza	3.7% 5/134 • Number of events 9 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	6.6% 8/121 • Number of events 12 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Infections and infestations Nasopharyngitis	17.9% 24/134 • Number of events 34 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	20.7% 25/121 • Number of events 55 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	4.5% 1/22 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Infections and infestations Pharyngitis	0.75% 1/134 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	5.8% 7/121 • Number of events 9 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Infections and infestations Upper respiratory tract infection	2.2% 3/134 • Number of events 3 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	9.9% 12/121 • Number of events 14 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Injury, poisoning and procedural complications Limb injury	2.2% 3/134 • Number of events 3 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	6.6% 8/121 • Number of events 8 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Injury, poisoning and procedural complications Procedural haemorrhage	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/121 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	13.6% 3/22 • Number of events 3 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Injury, poisoning and procedural complications Procedural hypotension	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/121 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	9.1% 2/22 • Number of events 2 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Injury, poisoning and procedural complications Procedural pain	1.5% 2/134 • Number of events 2 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	5.8% 7/121 • Number of events 8 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	40.9% 9/22 • Number of events 10 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Investigations Haemoglobin decreased	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	1.7% 2/121 • Number of events 2 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	13.6% 3/22 • Number of events 3 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Musculoskeletal and connective tissue disorders Arthralgia	8.2% 11/134 • Number of events 13 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	21.5% 26/121 • Number of events 40 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	9.1% 2/22 • Number of events 2 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Musculoskeletal and connective tissue disorders Back pain	6.0% 8/134 • Number of events 10 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	11.6% 14/121 • Number of events 17 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Musculoskeletal and connective tissue disorders Haemarthrosis	1.5% 2/134 • Number of events 2 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	6.6% 8/121 • Number of events 8 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	4.5% 1/22 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	3.0% 4/134 • Number of events 4 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	5.8% 7/121 • Number of events 10 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	5.8% 7/121 • Number of events 12 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Musculoskeletal and connective tissue disorders Pain in extremity	3.7% 5/134 • Number of events 6 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	6.6% 8/121 • Number of events 11 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Nervous system disorders Headache	11.9% 16/134 • Number of events 28 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	11.6% 14/121 • Number of events 21 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Psychiatric disorders Insomnia	2.2% 3/134 • Number of events 3 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.83% 1/121 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	9.1% 2/22 • Number of events 2 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Respiratory, thoracic and mediastinal disorders Cough	6.0% 8/134 • Number of events 11 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	7.4% 9/121 • Number of events 11 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Respiratory, thoracic and mediastinal disorders Epistaxis	6.0% 8/134 • Number of events 10 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	5.0% 6/121 • Number of events 6 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	0.00% 0/22 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Skin and subcutaneous tissue disorders Rash	0.75% 1/134 • Number of events 1 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	2.5% 3/121 • Number of events 6 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	9.1% 2/22 • Number of events 2 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.
Vascular disorders Haematoma	0.00% 0/134 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	2.5% 3/121 • Number of events 3 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.	9.1% 2/22 • Number of events 2 • Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years.

Additional Information

Therapeutic Area Head

Bayer AG

Phone: (+) 1-888-8422937

Email: clinical-trials-contact@bayer.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60