Trial Outcomes & Findings for Safety, Efficacy and PK of BIVV001 in Pediatric Patients With Hemophilia A (NCT NCT04759131)

NCT ID: NCT04759131

Last Updated: 2025-09-11

Results Overview

Inhibitor development was defined as an inhibitor result of greater than or equal to (\>=0.6) Bethesda units (BU/mL) that was confirmed by a second test result from a separate sample, drawn 2 to 4 weeks following the date when the original sample was drawn. Both tests must have been performed by the central laboratory using the Nijmegen modified Bethesda assay.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 74 participants
• Primary outcome timeframe: Baseline up to Week 52
• Results posted on: 2025-09-11

Participant Flow

Study was conducted at 40 active sites in 15 countries. A total of 79 pediatric participants were screened between 19 February 2021 to 09 February 2022, of which 5 participants had screen failure due to not meeting the eligibility criteria.

The study comprised of 2 age cohorts of children with severe hemophilia A: less than (<) 6 years and 6 to <12 years. A total of 74 participants were enrolled in this study.

Participant milestones

Measure	BIVV001: Participants Aged <6 Years Participants aged \<6 years received BIVV001 at a dose of 50 international units per kilogram (IU/kg) intravenous (IV) injection once-weekly (QW) prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Overall Study STARTED	38	36
Overall Study COMPLETED	36	36
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Measure	BIVV001: Participants Aged <6 Years Participants aged \<6 years received BIVV001 at a dose of 50 international units per kilogram (IU/kg) intravenous (IV) injection once-weekly (QW) prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Overall Study Investigator's discretion	1	0
Overall Study Subject withdrawal	1	0

Baseline Characteristics

Safety, Efficacy and PK of BIVV001 in Pediatric Patients With Hemophilia A

Baseline characteristics by cohort

Measure	BIVV001: Participants Aged <6 Years n=38 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=36 Participants Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	Total n=74 Participants Total of all reporting groups
Age, Continuous	3.69 years STANDARD_DEVIATION 1.21 • n=5 Participants	8.42 years STANDARD_DEVIATION 2.08 • n=7 Participants	5.99 years STANDARD_DEVIATION 2.91 • n=5 Participants
Age, Customized Children (1 to 5 years)	38 Participants n=5 Participants	0 Participants n=7 Participants	38 Participants n=5 Participants
Age, Customized Children (>=6 to 11 years)	0 Participants n=5 Participants	36 Participants n=7 Participants	36 Participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	38 Participants n=5 Participants	36 Participants n=7 Participants	74 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	30 Participants n=5 Participants	25 Participants n=7 Participants	55 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other or Not Reported	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to Week 52

Population: Analysis was performed on safety analysis set which included all participants who took at least 1 dose of study intervention.

Inhibitor development was defined as an inhibitor result of greater than or equal to (>=0.6) Bethesda units (BU/mL) that was confirmed by a second test result from a separate sample, drawn 2 to 4 weeks following the date when the original sample was drawn. Both tests must have been performed by the central laboratory using the Nijmegen modified Bethesda assay.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=38 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=36 Participants Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Number of Participants With Neutralising Antibodies (Development of Inhibitors) Directed Against Factor VIII	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Analysis was performed on FAS population.

ABR: annualized number of treated bleeding episodes (BE) per participant per year. ABR=number of treated BE during efficacy period (EP)/total number of days during EP*365.25. Treated BE:any occurrence of hemorrhage required administration of BIVV001. It started from 1st sign of bleed and ended no more than 72 hours after last injection to treat BE, any subsequent bleeding at same location/injections administered less than or equal to (<=) 72 hours apart from previous injection were considered same BE. Any injection after >72 hours post preceding one=considered 1st injection to treat new BE in same location. Any bleed at different location:considered as separate BE, regardless of time from last injection. EP=sum of all intervals of time during which participants were treated with BIVV001 according to study arms and treatment regimens. ABR:by negative binomial model with total number of treated BE during EP as response variable and log transformed EP duration (years) as offset variable.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=38 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=36 Participants Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Annualized Bleeding Rate (ABR): For Treated Bleeds	0.48 episodes per participant per year Interval 0.3 to 0.77	1.33 episodes per participant per year Interval 0.64 to 2.76

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Analysis was performed on FAS population. Sensitivity analysis excluded 1 participant who did not receive weekly prophylaxis treatment as specified in the protocol for an extended period of time.

ABR: annualized number of treated BE per participant per year. ABR = number of treated BE during EP/total number of days during EP*365.25. Treated BE: any occurrence of hemorrhage that required administration of BIVV001. It started from 1st sign of bleed and ended no more than 72 hours after last injection to treat BE, any subsequent bleeding at same location/injections administered <=72 hours apart from previous injection were considered same BE. Any injection to treat bleed, taken >72 hours after preceding one, was considered 1st injection to treat new bleeding episode in same location. Any bleed at different location: considered as separate BE, regardless of time from last injection. EP reflects sum of all intervals of time during which participants were treated with BIVV001 according to study arms and treatment regimens. ABR: using negative binomial (NB) model with total number of treated BE during EP as response variable and log-transformed EP duration (years) as offset variable.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=38 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=35 Participants Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Sensitivity Analysis: Annualized Bleeding Rate: For Treated Bleeds	0.48 episodes per participant per year Interval 0.3 to 0.77	0.75 episodes per participant per year Interval 0.41 to 1.4

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Analysis was performed on FAS population.

ABR:annualized number of all BE (treated and untreated)/participant/year. ABR=number of all BE during EP/total number of days during EP*365.25. BE:any occurrence of hemorrhage required administration of BIVV001. It started from 1st sign of bleed and ended no more than 72 hours after last injection to treat BE, any subsequent bleeding at same location/injections administered <=72 hours apart from previous injection were considered same BE. Any injection after >72 hours post preceding one=considered 1st injection to treat new BE in same location. Any bleed at different location: considered as separate BE, regardless of time from last injection. EP:sum of all intervals of time during which participants treated with BIVV001 according to study arms & treatment regimens. ABR:NB model with total number of treated BE during EP as response variable and log-transformed EP duration (years) as offset variable. Spontaneous:bleeding without contributing factor, Traumatic:bleeding with known reason.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=38 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=36 Participants Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Annualized Bleeding Rate for All Bleeding Episodes	2.78 episodes per participant per year Interval 1.39 to 5.58	2.85 episodes per participant per year Interval 1.59 to 5.12

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Analysis was performed on FAS population. Sensitivity analysis excluded 1 participant who did not receive weekly prophylaxis treatment as specified in the protocol for an extended period of time.

ABR: annualized number of all BE (treated & untreated)/participant/year. ABR=number of all BE during EP/total number of days during EP*365.25. BE: any hemorrhage occurrence required administration of BIVV001. It started from 1st sign of bleed & ended no more than 72 hours after last injection to treat BE, any subsequent bleeding at same location/injections administered <=72 hours apart from previous injection were considered same BE. Any bleed at different location: considered as separate BE, regardless of time from last injection. EP: sum of all intervals of time during which participants treated with BIVV001 according to study arms and treatment regimens. ABR: estimated by NB model with total number of treated BE during EP as response variable and log-transformed EP duration (years) as offset variable. Spontaneous: bleeding without contributing factor (definite trauma/antecedent strenuous activity). Traumatic: bleeding with known/believed reason.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=38 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=35 Participants Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Sensitivity Analysis: Annualized Bleeding Rate for All Bleeding Episodes	2.78 episodes per participant per year Interval 1.39 to 5.58	2.32 episodes per participant per year Interval 1.3 to 4.13

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Analysis was performed on FAS population.

ABR: annualized number of treated bleeding episodes per participant per year. ABR = number of all BE during EP/total number of days during EP*365.25. EP reflects sum of all intervals of time during which participants were treated with BIVV001 according to study arms and treatment regimens. Treated BE: episode that started from 1st sign of bleed and ended no more than 72 hours after last injection to treat bleeding episode, any subsequent bleeding at same location/injections administered <=72 hours apart from previous injection were considered same bleeding episode. Any injection to treat bleed, taken >72 hours after preceding one was considered 1st injection to treat new BE in same location. Any bleed at different location was considered as separate bleeding episode, regardless of time from last injection. Spontaneous bleeding: BE without contributing factor (definite trauma/antecedent "strenuous" activity). Traumatic bleeding: BE with known/believed reason for bleed.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=38 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=36 Participants Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Annualized Bleeding Rate by Type of Bleed (Spontaneous, Traumatic and Unknown Type) Spontaneous	0.17 episodes per participant per year Interval 0.08 to 0.38	0.14 episodes per participant per year Interval 0.04 to 0.53
Annualized Bleeding Rate by Type of Bleed (Spontaneous, Traumatic and Unknown Type) Traumatic	0.28 episodes per participant per year Interval 0.14 to 0.55	0.59 episodes per participant per year Interval 0.31 to 1.14
Annualized Bleeding Rate by Type of Bleed (Spontaneous, Traumatic and Unknown Type) Unknown type	0.03 episodes per participant per year Interval 0.0 to 0.2	0.59 episodes per participant per year Interval 0.12 to 3.02

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Analysis was performed on FAS population. Sensitivity analysis excluded 1 participant who did not receive weekly prophylaxis treatment as specified in the protocol for an extended period of time.

ABR: annualized number of treated bleeding episodes per participant per year. ABR = number of all BE during EP/total number of days during EP*365.25. EP reflects sum of all intervals of time during which participants were treated with BIVV001 according to study arms and treatment regimens. Treated BE: episode that started from 1st sign of bleed and ended no more than 72 hours after last injection to treat bleeding episode, any subsequent bleeding at same location/injections administered <=72 hours apart from previous injection were considered same bleeding episode. Any injection to treat bleed, taken >72 hours after preceding one, was considered 1st injection to treat new BE in same location. Any bleed at different location was considered as separate bleeding episode, regardless of time from last injection. Spontaneous bleeding: BE without contributing factor (definite trauma/antecedent "strenuous" activity). Traumatic bleeding: BE with known/believed reason for bleed.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=38 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=35 Participants Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Sensitivity Analysis: Annualized Bleeding Rate by Type of Bleed (Spontaneous, Traumatic and Unknown Type) Spontaneous	0.17 episodes per participant per year Interval 0.08 to 0.38	0.15 episodes per participant per year Interval 0.04 to 0.55
Sensitivity Analysis: Annualized Bleeding Rate by Type of Bleed (Spontaneous, Traumatic and Unknown Type) Traumatic	0.28 episodes per participant per year Interval 0.14 to 0.55	0.52 episodes per participant per year Interval 0.26 to 1.04
Sensitivity Analysis: Annualized Bleeding Rate by Type of Bleed (Spontaneous, Traumatic and Unknown Type) Unknown type	0.03 episodes per participant per year Interval 0.0 to 0.2	0.09 episodes per participant per year Interval 0.03 to 0.27

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Analysis was performed on FAS population.

ABR: annualized number of treated bleeding episodes per participant per year. ABR = number of all BE during EP/total number of days during EP*365.25. Efficacy period reflects sum of all intervals of time during which participants were treated with BIVV001 according to study arms and treatment regimens. Treated bleeding episode: episode that started from 1st sign of bleed and ended no more than 72 hours after last injection to treat bleeding episode, any subsequent bleeding at same location/injections administered <=72 hours apart from previous injection were considered same bleeding episode. Any injection >72 hours after preceding one, was considered 1st injection to treat new BE in same location. Any bleed at different location was considered as separate bleeding episode, regardless of time from last injection. Spontaneous bleeding: BE without contributing factor (definite trauma/antecedent "strenuous" activity). Traumatic bleeding: BE with known/believed reason for bleed.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=38 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=36 Participants Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal and Skin/Mucosa) Joint	0.19 episodes per participant per year Standard Deviation 0.63	0.99 episodes per participant per year Standard Deviation 3.62
Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal and Skin/Mucosa) Muscle	0.03 episodes per participant per year Standard Deviation 0.16	0.17 episodes per participant per year Standard Deviation 0.51
Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal and Skin/Mucosa) Internal	0.08 episodes per participant per year Standard Deviation 0.28	0.06 episodes per participant per year Standard Deviation 0.35
Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal and Skin/Mucosa) Skin/mucosa	0.16 episodes per participant per year Standard Deviation 0.38	0.25 episodes per participant per year Standard Deviation 0.60

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Analysis was performed on FAS population. Sensitivity analysis excluded 1 participant who did not receive weekly prophylaxis treatment as specified in the protocol for an extended period of time.

ABR: annualized number of treated bleeding episodes per participant per year. ABR = number of all BE during EP/total number of days during EP*365.25. EP reflects sum of all intervals of time during which participants were treated with BIVV001 according to study arms & treatment regimens. Treated BE: episode that started from 1st sign of bleed and ended no more than 72 hours after last injection to treat bleeding episode any subsequent bleeding at same location/injections administered <=72 hours apart from previous injection were considered same bleeding episode. Any injection to treat bleed, taken >72 hours after preceding one, was considered 1st injection to treat new BE in same location. Any bleed at different location was considered as separate bleeding episode, regardless of time from last injection. Spontaneous bleeding: BE without contributing factor (definite trauma/antecedent "strenuous" activity). Traumatic bleeding: BE with known/believed reason for bleed.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=38 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=35 Participants Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Sensitivity Analysis: Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal and Skin/Mucosa) Joint	0.19 episodes per participant per year Standard Deviation 0.63	0.40 episodes per participant per year Standard Deviation 0.93
Sensitivity Analysis: Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal and Skin/Mucosa) Muscle	0.03 episodes per participant per year Standard Deviation 0.16	0.17 episodes per participant per year Standard Deviation 0.52
Sensitivity Analysis: Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal and Skin/Mucosa) Internal	0.08 episodes per participant per year Standard Deviation 0.28	0.06 episodes per participant per year Standard Deviation 0.35
Sensitivity Analysis: Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal and Skin/Mucosa) Skin/mucosa	0.16 episodes per participant per year Standard Deviation 0.38	0.26 episodes per participant per year Standard Deviation 0.61

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Analysis was performed on FAS. Here, 'overall number of participants analyzed = participants with available data for this outcome measure.

FVIII activity level was measured using activated partial thromboplastin time (aPTT)-based one stage clotting assay. Percentage of participants who achieved steady-state trough FVIII activity levels above (>) 1%, 3%, 5%, 10%, 15%, and 20% were reported in this outcome measure. Participants were counted in more than one category, as applicable.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=32 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=29 Participants Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Percentage of Participants Achieving FVIII Activity Levels Above 1%, 3%, 5%, 10%, 15%, and 20% >20%	3.1 percentage of participants	6.9 percentage of participants
Percentage of Participants Achieving FVIII Activity Levels Above 1%, 3%, 5%, 10%, 15%, and 20% >1%	100 percentage of participants	100 percentage of participants
Percentage of Participants Achieving FVIII Activity Levels Above 1%, 3%, 5%, 10%, 15%, and 20% >3%	100 percentage of participants	100 percentage of participants
Percentage of Participants Achieving FVIII Activity Levels Above 1%, 3%, 5%, 10%, 15%, and 20% >5%	75.0 percentage of participants	100 percentage of participants
Percentage of Participants Achieving FVIII Activity Levels Above 1%, 3%, 5%, 10%, 15%, and 20% >10%	18.8 percentage of participants	51.7 percentage of participants
Percentage of Participants Achieving FVIII Activity Levels Above 1%, 3%, 5%, 10%, 15%, and 20% >15%	9.4 percentage of participants	6.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Analysis was performed on FAS. Here, 'overall number of units analyzed' = total number of treated bleeding episodes.

A bleeding episode was defined as an episode that started from 1st sign of bleed and ended no more than 72 hours after last injection to treat bleeding episode, any subsequent bleeding at same location or injections administered <=72 hours apart from previous injection were considered same bleeding episode. Any injection to treat bleed, taken >72 hours after preceding one, was considered 1st injection to treat new BE in same location. Any bleed at different location was considered as separate bleeding episode, regardless of time from last injection.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=17 Treated bleeding episode Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=47 Treated bleeding episode Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Number of Injections of BIVV001 Required to Treat a Bleeding Episode	1.12 injections per bleeding episode Standard Deviation 0.33	1.30 injections per bleeding episode Standard Deviation 0.69

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Analysis was performed on FAS excluding 1 participant who did not receive weekly prophylaxis treatment as specified in the protocol for an extended period of time. Here, 'overall number of units analyzed' = total number of treated bleeding episodes.

A bleeding episode was defined as an episode that started from 1st sign of bleed and ended no more than 72 hours after last injection to treat bleeding episode, any subsequent bleeding at same location or injections administered <=72 hours apart from previous injection were considered same bleeding episode. Any injection to treat bleed, taken >72 hours after preceding one, was considered 1st injection to treat new BE in same location. Any bleed at different location: considered as separate BE, regardless of time from last injection.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=17 Treated bleeding episode Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=26 Treated bleeding episode Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Sensitivity Analysis: Number of Injections of BIVV001 Required to Treat a Bleeding Episode	1.12 injections per bleeding episode Standard Deviation 0.33	1.00 injections per bleeding episode Standard Deviation 0.00

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Analysis was performed on FAS population. Here, 'overall number of units analyzed' = total number of treated bleeding episodes.

A bleeding episode was defined as an episode that started from 1st sign of bleed and ended no more than 72 hours after last injection to treat bleeding episode, any subsequent bleeding at same location or injections administered <=72 hours apart from previous injection were considered same bleeding episode. Any injection to treat bleed, taken >72 hours after preceding one, was considered 1st injection to treat new BE in same location. Any bleed at different location: considered as separate BE, regardless of time from last injection. Percentage of bleeding episodes (of all bleeding episodes occurred) which were treated with single injection was reported in this outcome measure.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=17 Treated bleeding episode Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=47 Treated bleeding episode Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Percentage of Bleeding Episodes Treated With a Single Injection of BIVV001	88.2 percentage of bleeding episodes	78.7 percentage of bleeding episodes

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Analysis was performed on FAS, excluding the participant who did not receive the weekly prophylaxis treatment as per protocol for an extended period of time. Here, 'overall number of units analyzed' = total number of treated bleeding episodes.

A bleeding episode was defined as an episode that started from 1st sign of bleed and ended no more than 72 hours after last injection to treat bleeding episode, any subsequent bleeding at same location or injections administered <=72 hours apart from previous injection were considered same bleeding episode. Any injection to treat bleed, taken >72 hours after preceding one, was considered 1st injection to treat new BE in same location. Any bleed at different location: considered as separate BE, regardless of time from last injection. Percentage of bleeding episodes (of all bleeding episodes occurred) which were treated with single injection was reported in this outcome measure.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=17 Treated bleeding episode Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=26 Treated bleeding episode Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Sensitivity Analysis: Percentage of Bleeding Episodes Treated With a Single Injection of BIVV001	88.2 percentage of bleeding episodes	100 percentage of bleeding episodes

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Analysis was performed on FAS. Here, 'overall number of units analyzed' = total number of treated bleeding episodes.

A bleeding episode was defined as an episode that started from 1st sign of bleed and ended no more than 72 hours after last injection to treat bleeding episode, any subsequent bleeding at same location or injections administered <=72 hours apart from previous injection were considered same bleeding episode. Any injection to treat bleed, taken >72 hours after preceding one, was considered 1st injection to treat new BE in same location. Any bleed at different location: considered as separate BE, regardless of time from last injection. Total dose was expressed in unit: International units per kilogram (IU/kg).

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=17 Treated bleeding episode Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=47 Treated bleeding episode Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Total Dose of BIVV001 Required to Treat a Bleeding Episode	52.29 IU/kg Standard Deviation 15.84	66.90 IU/kg Standard Deviation 37.01

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Analysis was performed on FAS, excluding 1 participant who did not receive weekly prophylaxis treatment for an extended period of time. Here, 'overall number of units analyzed' = total number of treated bleeding episodes.

A bleeding episode was defined as an episode that started from 1st sign of bleed and ended no more than 72 hours after last injection to treat bleeding episode, any subsequent bleeding at same location or injections administered <=72 hours apart from previous injection were considered same bleeding episode. Any injection to treat bleed, taken >72 hours after preceding one, was considered 1st injection to treat new BE in same location. Any injection after >72 hours post preceding one, was considered 1st injection to treat new BE in same location. Any bleed at different location: considered as separate BE, regardless of time from last injection. Total dose was expressed in unit: IU/kg.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=17 Treated bleeding episode Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=26 Treated bleeding episode Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Sensitivity Analysis: Total Dose of BIVV001 Required to Treat a Bleeding Episode	52.29 IU/kg Standard Deviation 15.84	50.39 IU/kg Standard Deviation 6.71

SECONDARY outcome

Timeframe: Week 13 and Week 52/End of study (EOS)/Early termination (ET)

Population: Analysis was performed on FAS. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

Physicians assessed participant's response to BIVV001 treatment using 4-point response scale categorized as: Excellent= BE responded to fewer than/usual number of injections/less than/usual dose of FVIII/rate of breakthrough bleeding during prophylaxis was <= that usually observed; Effective = most BE responded to same number of injections and dose, but some required more injections/higher doses/there was minor increase in rate of breakthrough bleeding; partially effective = BE most often required more injections and/or higher doses than expected/adequate breakthrough bleeding prevention during prophylaxis required more frequent injections and/or higher doses; Ineffective = routine failure to control hemostasis or hemostatic control required additional agents.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=37 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=36 Participants Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Physicians' Global Assessment (PGA) of Participant's Response to BIVV001 Treatment Based on a 4-point Response Scale Week 13: Excellent	37 Participants	34 Participants
Physicians' Global Assessment (PGA) of Participant's Response to BIVV001 Treatment Based on a 4-point Response Scale Week 13: Effective	0 Participants	2 Participants
Physicians' Global Assessment (PGA) of Participant's Response to BIVV001 Treatment Based on a 4-point Response Scale Week 13: Partially effective	0 Participants	0 Participants
Physicians' Global Assessment (PGA) of Participant's Response to BIVV001 Treatment Based on a 4-point Response Scale Week 13: Ineffective	0 Participants	0 Participants
Physicians' Global Assessment (PGA) of Participant's Response to BIVV001 Treatment Based on a 4-point Response Scale Week 52/EOS/ET: Excellent	37 Participants	36 Participants
Physicians' Global Assessment (PGA) of Participant's Response to BIVV001 Treatment Based on a 4-point Response Scale Week 52/EOS/ET: Effective	0 Participants	0 Participants
Physicians' Global Assessment (PGA) of Participant's Response to BIVV001 Treatment Based on a 4-point Response Scale Week 52/EOS/ET: Partially effective	0 Participants	0 Participants
Physicians' Global Assessment (PGA) of Participant's Response to BIVV001 Treatment Based on a 4-point Response Scale Week 52/EOS/ET: Ineffective	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Analysis was performed on FAS population. Here, 'overall number of units analyzed' = number of injections with a response.

Participant's response to the 1st injection of BIVV001 treatment for treating a bleed was evaluated by ISTH 4-point response scale categorized as: Excellent (complete pain relief/complete resolution of signs of bleeding), Good (significant pain relief /improvement in signs of bleeding), Moderate (modest pain relief/improvement in signs of bleeding) and none (no or minimal improvement/condition worsened). Assessed approximately 72 hours after initial treatment for BE. Bleeding episode: an episode that started from 1st sign of bleed and ended no more than 72 hours after last treatment for bleed, within which any symptoms of bleeding at same location/injections <=72 hours apart were considered same BE. Any injection after >72 hours post preceding one=considered 1st injection to treat new BE in same location. Any bleed at different location: considered as separate BE, regardless of time from last injection. Participants were counted in more than one category, as applicable.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=16 Injections with a response Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=24 Injections with a response Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Participant's Response to BIVV001 Treatment Based on the International Society on Thrombosis and Haemostasis (ISTH) 4-point Response Scale Excellent	14 Injections with a response	22 Injections with a response
Participant's Response to BIVV001 Treatment Based on the International Society on Thrombosis and Haemostasis (ISTH) 4-point Response Scale Good	1 Injections with a response	2 Injections with a response
Participant's Response to BIVV001 Treatment Based on the International Society on Thrombosis and Haemostasis (ISTH) 4-point Response Scale Moderate	1 Injections with a response	0 Injections with a response
Participant's Response to BIVV001 Treatment Based on the International Society on Thrombosis and Haemostasis (ISTH) 4-point Response Scale None	0 Injections with a response	0 Injections with a response

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Analysis was performed on FAS population.

Total annualized BIVV001 consumption (in IU/kg) was calculated for each participant as: Total IU/kg of BIVV001 during EP divided by total number of days during EP*365.25. EP reflects the sum of all intervals of time during which participants were treated with BIVV001 according to the study arms and treatment regimens.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=38 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=36 Participants Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Total Annualized BIVV001 Consumption Per Participant	3115.57 IU/kg per participant per year Standard Deviation 488.64	2884.67 IU/kg per participant per year Standard Deviation 207.88

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Analysis was performed on FAS population.

AJBR: annualized number of joint bleeding/participant/year. ABR = number of treated joint BE during EP divided by total number of days during EP*365.25. Joint BE: unusual sensation in joint ('aura') along with 1) increasing swelling/warmth over skin, joint; 2) increasing pain or 3) progressive loss of range of motion/difficulty in using limb compared to Baseline. BE: episode started from 1st sign of bleed & ended no more than 72 hours after last treatment for bleed, within which any symptoms of bleeding at same location/injections <=72 hours apart considered same BE. Any injection after >72 hours post preceding one=1st injection to treat new BE in same location. Any bleed at different location=separate BE, regardless of time from last injection. EP: sum of all intervals of time during which participants treated with BIVV001 per study arms and treatment regimens. ABR:NB model with total number of treated BE during EP (response variable) & log-transformed EP duration (offset variable).

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=38 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=36 Participants Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Annualized Joint Bleeding Rate (AJBR)	0.19 joint BE per participant per year Interval 0.06 to 0.62	0.99 joint BE per participant per year Interval 0.38 to 2.6

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Analysis was performed on FAS population. Sensitivity analysis excluded 1 participant who did not receive weekly prophylaxis treatment as specified in the protocol for an extended period of time.

AJBR: annualized number of joint bleeding/participant/year. ABR = number of treated joint BE during EP divided by total number of days during EP*365.25. Joint BE: unusual sensation in joint ('aura') along with 1) increasing swelling/warmth over skin, joint; 2) increasing pain or 3) progressive loss of range of motion/difficulty in using limb compared to Baseline. BE: episode started from 1st sign of bleed & ended no more than 72 hours after last treatment for bleed, within which any symptoms of bleeding at same location/injections <=72 hours apart considered same BE. Any injection after >72 hours post preceding one=1st injection to treat new BE in same location. Any bleed at different location=separate BE, regardless of time from last injection. EP: sum of all intervals of time during which participants treated with BIVV001 per study arms and treatment regimens. ABR: NB model with total number of treated BE during EP (response variable) & log-transformed EP duration (offset variable).

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=38 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=35 Participants Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Sensitivity Analysis: Annualized Joint Bleeding Rate (AJBR)	0.19 joint BE per participant per year Interval 0.06 to 0.62	0.41 joint BE per participant per year Interval 0.19 to 0.89

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on FAS population. Here, 'number analyzed' = participants with available data for each specified category.

HJHS is a validated 11-item scoring tool developed for the assessment of joint health in participants with hemophilia. Following domains were assessed for elbows, knee and ankle joints: swelling (score 0 = no swelling to 3=severe), duration of swelling (score 0 = no swelling and 1 = >=6 months), muscle atrophy (score 0 = none to 2 = severe), crepitus on motion (score 0 = none to 2=severe), flexion loss (score 0 = <5' to 3 = >20'), extension loss (score 0 = <5' to 3 = >20'), joint pain (score 0 = no pain through active range of motion to 2 = pain through active range) and strength (score 0 = holds test position with maximum resistance to 4 = trace/no muscle contraction), for each item 0 = no damage and higher score = severe damage.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=38 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=36 Participants Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Change From Baseline in Hemophilia Joint Health Score Domain Score at Week 52 Swelling	0.0 score on a scale Standard Deviation 0.0	-0.1 score on a scale Standard Deviation 0.6
Change From Baseline in Hemophilia Joint Health Score Domain Score at Week 52 Duration Of Swelling	0.1 score on a scale Standard Deviation 0.2	-0.0 score on a scale Standard Deviation 0.2
Change From Baseline in Hemophilia Joint Health Score Domain Score at Week 52 Muscle Atrophy	0.0 score on a scale Standard Deviation 0.0	-0.1 score on a scale Standard Deviation 0.4
Change From Baseline in Hemophilia Joint Health Score Domain Score at Week 52 Crepitus On Motion	0.1 score on a scale Standard Deviation 0.2	-0.1 score on a scale Standard Deviation 0.5
Change From Baseline in Hemophilia Joint Health Score Domain Score at Week 52 Flexion Loss	-0.9 score on a scale Standard Deviation 4.1	-0.1 score on a scale Standard Deviation 0.6
Change From Baseline in Hemophilia Joint Health Score Domain Score at Week 52 Extension Loss	-0.2 score on a scale Standard Deviation 1.0	0.2 score on a scale Standard Deviation 0.9
Change From Baseline in Hemophilia Joint Health Score Domain Score at Week 52 Joint Pain	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.4
Change From Baseline in Hemophilia Joint Health Score Domain Score at Week 52 Strength	1.3 score on a scale Standard Deviation 10.0	-0.8 score on a scale Standard Deviation 4.2

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on FAS population. Here, 'number analyzed' = participants with available data for each specified category and '0' in the number analyzed field signifies that no participants were aged 8 to \<12 years in arm "BIVV001: Participants aged \<6 Years".

Haemo-QoL kids short version: used to measure physical and emotional impacts on quality of life in children & adolescent with hemophilia. It was administered to children & their caregivers. Short version for children containing 16 items (4 to 7 years) and 35 items (8 to <12 years) were selected in this study. This version covers 9 dimensions relevant for children's HRQoL (physical health, feelings, view of yourself, family, friends, other people, sports and school, dealing with hemophilia & treatment). Items were rated along 5 response options: never, seldom, sometimes, often and always, higher scores=greater impairment. Raw score for each domain were transformed to scale ranged between 0 to 100, where lower score=better HRQoL. Haem- A-QoL total score=average of all domain scores and ranged from 0 to 100, where lower scores=better QoL.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=10 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=14 Participants Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Change From Baseline in Hemophilia Quality of Life Questionnaire (Haemo-QoL) Kids Short Version Total Score at Week 52 for Children Participants (Aged 4 to 7 and 8 to <12 Years) 4 to 7 years	-5.31 score on a scale Standard Deviation 10.83	4.69 score on a scale Standard Deviation 5.41
Change From Baseline in Hemophilia Quality of Life Questionnaire (Haemo-QoL) Kids Short Version Total Score at Week 52 for Children Participants (Aged 4 to 7 and 8 to <12 Years) 8 to <12 years	—	-9.79 score on a scale Standard Deviation 12.18

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on FAS population. Here, 'number analyzed' = participants with available data for each specified category and '0' in the number analyzed field signifies that no participants were aged 8 to \<12 years in arm "BIVV001: Participants aged \<6 Years".

Haemo-QoL parent proxy short version: used to measure physical and emotional impacts on quality of life in children and adolescent with hemophilia. It was administered to children & their caregivers. Short version for children's caregivers containing 16 items (participants 4 to 7 years) and 35 items (participants 8 to <12 years) were selected in this study. This version covers 9 dimensions relevant for children's HRQoL (physical health, feelings, view of yourself, family, friends, other people, sports and school, dealing with hemophilia and treatment). Items are rated along 5 response options: never, seldom, sometimes, often and always, higher scores=greater impairment. Raw score for each domain: transformed to scale ranged between 0 to 100, lower score=better HRQoL. Haem-A-QoL total score=average of all domain scores and ranged from 0 to 100, lower scores=better quality of life. Haemo-QoL Total Score as per parent's evaluation was reported in this outcome measure.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=19 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=13 Participants Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Change From Baseline in Hemophilia Quality of Life Questionnaire Parent Proxy Short Version Total Score at Week 52 for Children Participants (Aged 4 to 7 and 8 to <12 Years): Parent's Evaluation 4 to 7 years	-3.21 score on a scale Standard Deviation 12.23	-1.17 score on a scale Standard Deviation 11.08
Change From Baseline in Hemophilia Quality of Life Questionnaire Parent Proxy Short Version Total Score at Week 52 for Children Participants (Aged 4 to 7 and 8 to <12 Years): Parent's Evaluation 8 to <12 years	—	-4.05 score on a scale Standard Deviation 10.77

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on FAS population. Here, 'Overall number of participants analyzed' = participants with available data for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for arm 'BIVV001: Participants aged \<6 years'.

Haemo-QoL kids short version: used to measure physical and emotional impacts on quality of life in children and adolescent with hemophilia. It was administered to children and their caregivers. Short version for children containing 35 items (8 to <12 years) were selected in this study. This version covers 9 dimensions considered relevant for the children's HRQoL (physical health, feelings, view of yourself, family, friends, other people, sports and school, dealing with hemophilia and treatment). Items are rated along 5 response options: never, seldom, sometimes, often and always, higher scores=greater impairment. Raw score for physical health domain were transformed to scale ranged between 0 to 100, where lower score=better HRQoL. Change from baseline in physical Health domain score was reported in this outcome measure.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=10 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Change From Baseline in Hemophilia Quality of Life Questionnaire Kids Short Version Physical Health Domain Score at Week 52 for Children Participants (Aged 8 to <12 Years)	-10.63 score on a scale Standard Deviation 14.75	—

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on FAS population. Here, 'Overall number of participants analyzed' = participants with available data for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for arm 'BIVV001: Participants aged \<6 years'.

Haemo-QoL parent proxy short version: used to measure physical & emotional impacts on quality of life in children & adolescent with hemophilia. It was administered to children & their caregivers. Short version for children's caregivers containing 35 items (participants 8 to <12 years) were selected in this study. This version covers 9 dimensions relevant for children's HRQoL (physical health, feelings, view of yourself, family, friends, other people, sports and school, dealing with hemophilia & treatment). Items are rated along 5 response options: never, seldom, sometimes, often and always, higher scores=greater impairment. Raw score for physical health domain were transformed to scale ranged between 0 and 100, where lower score=better HRQoL. Change from baseline in physical health domain score as per parent's evaluation was reported in this outcome measure.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=9 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Change From Baseline in Hemophilia Quality of Life Questionnaire Parent Proxy Short Version Physical Health Domain Score at Week 52 for Children Participants (Aged 8 to <12 Years): Parent's Evaluation	-7.64 score on a scale Standard Deviation 11.60	—

SECONDARY outcome

Timeframe: Week 52

Population: Analysis was performed on FAS population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and had at least 12 months of continuous exposure. 'Overall number of units analyzed' = total number of target joints at Baseline from participants with at least 12 months continuous exposure. Here "0" in 'overall number of participants analyzed' signifies that none of the participants had at least 12 months of continuous exposure.

A target joint at Baseline was defined as a major joint with >=3 spontaneous bleeding episodes in a consecutive 6 month period prior to entry to the study, captured at Baseline. A target joint resolved was defined as <=2 spontaneous bleeds into that joint during 12 months of continuous exposure (defined as treatment regimen period >=52 weeks). Total number of target joints resolved at Week 52 were reported.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=2 Total number of target joints Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Total Number of Target Joints Resolved in Participants at Week 52	—	2 Target joints resolved

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on FAS population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

HJHS is a validated 11-item scoring tool developed for the assessment of joint health in participants with hemophilia. It comprised an evaluation of the elbows, knee and ankle joints: swelling (0 to 3), duration of swelling (0 to 1), muscle atrophy (0 to 2), crepitus on motion (0 to 2), flexion loss (0 to 3), extension loss (0 to 3), joint pain (0 to 2) and strength (0 to 4), in each item 0 = none and higher score = severe damage and global gait (walking, stairs, running, hopping on 1 leg) scored on scale ranged from 0 to 4, where 0 = all skills in normal limit and 4 = no skills within normal limits). Total HJHS score = sum of joint totals (0 to 120) + general gait (1 to 4) and ranged from 0 (no joint damage) to 124 (severe joint damage), where higher score indicated severe joint damage.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=18 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=33 Participants Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Change From Baseline in Hemophilia Joint Health Score (HJHS) Total Score at Week 52	0.2 score on a scale Standard Deviation 8.3	-1.1 score on a scale Standard Deviation 4.3

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Analysis was performed on a surgery subgroup population which included all participants who had undergone major surgery after the 1st dose of study drug. Here, 'overall number of participants analyzed' = participants with major surgeries during the specified period (defined as the date and time of the first dose of study drug up to the last dose of study drug) and 'overall number of units analyzed' = number of major surgeries during the specified period occurred in participants analyzed.

The Investigators/Surgeons who complete the surgical procedures assess the participant's response to surgery with BIVV001 treatment using a 4-point scale, where responses were categorized as: 1 = Excellent, 2 = Good, 3 = Fair, and 4 = Poor/none. Higher score indicated worst response. This assessment was performed 24 hours after the surgery. A surgery can be counted in more than one response category. As pre-specified, this outcome measure was planned to be analyzed combinedly for both the cohorts (participants <6 years and participants 6 to <12 years) and presented under a single reporting group.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=2 Number of major surgeries Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Investigators' or Surgeons' Assessment of Participant's Hemostatic Response to BIVV001 Treatment Excellent or Good	2 major surgeries	—
Investigators' or Surgeons' Assessment of Participant's Hemostatic Response to BIVV001 Treatment Excellent	2 major surgeries	—
Investigators' or Surgeons' Assessment of Participant's Hemostatic Response to BIVV001 Treatment Good	0 major surgeries	—
Investigators' or Surgeons' Assessment of Participant's Hemostatic Response to BIVV001 Treatment Fair	0 major surgeries	—
Investigators' or Surgeons' Assessment of Participant's Hemostatic Response to BIVV001 Treatment Poor/none	0 major surgeries	—

SECONDARY outcome

Timeframe: During the perioperative period (any time during Baseline up to Week 52)

Population: Analysis was performed on surgery subgroup population. Here, 'overall number of participants analyzed' = participants with major surgeries during the specified period and 'overall number of units analyzed' = number of major surgeries during the specified period occurred in participants analyzed. As pre-specified, this outcome measure was planned to be analyzed combinedly for both the cohorts (participants \<6 years and participants 6 to \<12 years) and presented under a single reporting group.

Perioperative period was time lapse surrounding the surgical act which was divided into 3 stages: preoperative (4 weeks prior to surgery), operative (during the surgery) and post-operative (24-hour post-surgery). The number of injections to maintain hemostasis (process to prevent and stop bleeding from blood vessel) per surgery included all injections from loading dose (i.e., the preoperative injection, administered either on the day of surgery or one day prior to the surgery), to end of surgery. Major surgery: defined as any invasive operative procedure that required any of the following: opening into major body cavity (e.g., abdomen, thorax, skull); operation on a joint; removal of an organ; dental extraction of any molar teeth or >=3 non-molar teeth; operative alteration of normal anatomy; crossing of a mesenchymal barrier (e.g., pleura, peritoneum, dura).

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=2 Number of major surgeries Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Number of Injections Per Surgery Required to Maintain Hemostasis During Perioperative Period for Major Surgery One injection	2 Major surgeries	—
Number of Injections Per Surgery Required to Maintain Hemostasis During Perioperative Period for Major Surgery Two injection	0 Major surgeries	—
Number of Injections Per Surgery Required to Maintain Hemostasis During Perioperative Period for Major Surgery Three injection	0 Major surgeries	—
Number of Injections Per Surgery Required to Maintain Hemostasis During Perioperative Period for Major Surgery Four injection	0 Major surgeries	—
Number of Injections Per Surgery Required to Maintain Hemostasis During Perioperative Period for Major Surgery >Four injection	0 Major surgeries	—

SECONDARY outcome

Timeframe: During the perioperative period (any time during Baseline up to Week 52)

Population: Analysis was performed on surgery subgroup population. Here, 'overall number of participants analyzed' = participants with major surgeries during the specified period and 'overall number of units analyzed' = number of major surgeries during the specified period occurred in participants analyzed. As pre-specified, this outcome measure was planned to be analyzed combinedly for both the cohorts (participants \<6 years and participants 6 to \<12 years) and presented under a single reporting group.

The perioperative period was the time lapse surrounding the surgical act which was divided into 3 stages: preoperative (4 weeks prior to surgery), operative (during the surgery) and post-operative (24-hour post-surgery). The number of blood component transfusions used during perioperative period were summarized categorically (0, 1, 2, 3 and >3) for all major surgeries for the surgery subgroup. Major surgery: defined as any invasive operative procedure that required any of the following: opening into major body cavity (e.g., abdomen, thorax, skull); operation on a joint; removal of an organ; dental extraction of any molar teeth or >=3 non-molar teeth; operative alteration of normal anatomy; crossing of a mesenchymal barrier (e.g., pleura, peritoneum, dura).

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=2 Number of major surgeries Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Number of Blood Component Transfusions Used During Perioperative Period for Major Surgery Zero	2 Major surgeries	—
Number of Blood Component Transfusions Used During Perioperative Period for Major Surgery One	0 Major surgeries	—
Number of Blood Component Transfusions Used During Perioperative Period for Major Surgery Two	0 Major surgeries	—
Number of Blood Component Transfusions Used During Perioperative Period for Major Surgery Three	0 Major surgeries	—
Number of Blood Component Transfusions Used During Perioperative Period for Major Surgery >Three	0 Major surgeries	—

SECONDARY outcome

Timeframe: Day -1 to Day 14

Population: Analysis was performed on surgery subgroup population. Here, 'overall number of participants analyzed' = participants with major surgeries during the specified period and 'overall number of units analyzed' = number of major surgeries with BIVV001 administration within Day -1 to Day 14. As pre-specified, this outcome measure was planned to be analyzed combinedly for both the cohorts (participants \<6 years and participants 6 to \<12 years) and presented under a single reporting group.

Perioperative period: time lapse surrounding surgical act which was divided into 3 stages: preoperative (4 weeks prior to surgery), operative (during the surgery) and post-operative (24-hour post-surgery). Total BIVV001 consumption were summarized from the loading dose (the day before surgery, i.e., on Day -1) up to 2 weeks following the surgery (i.e., Day 14) and were reported in this outcome measure.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=2 Number of major surgeries Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Total BIVV001 Consumption From Day -1 to 14 During Perioperative Period for Major Surgery	201.97 IU/kg per major surgery Standard Deviation 29.42	—

SECONDARY outcome

Timeframe: During the perioperative period (any time during Baseline up to Week 52)

Population: Analysis was performed on surgery subgroup population. Here, 'overall number of participants analyzed' = participants with major surgeries during the specified period and 'overall number of units analyzed' = number of major surgeries during the specified period occurred in participants analyzed. As pre-specified, this outcome measure was planned to be analyzed combinedly for both the cohorts (participants \<6 years and participants 6 to \<12 years) and presented under a single reporting group.

The perioperative period was the time lapse surrounding the surgical act which was divided into 3 stages: preoperative (4 weeks prior to surgery), operative (during the surgery) and post-operative (24-hour post-surgery). The type of blood component (Red blood cell, platelet, fresh frozen plasma, whole blood and other) transfusions used were summarized for all major surgeries. Post-operative referred to the day following the end of surgery to the date of hospital discharge. Major surgery: defined as any invasive operative procedure that required any of the following: opening into major body cavity (e.g., abdomen, thorax, skull); operation on a joint; removal of an organ; dental extraction of any molar teeth or >=3 non-molar teeth; operative alteration of normal anatomy; crossing of a mesenchymal barrier (e.g., pleura, peritoneum, dura).

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=2 Number of major surgeries Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Type of Blood Component Transfusions Used During Perioperative Period for Major Surgery Red Blood Cell	0 Major surgeries	—
Type of Blood Component Transfusions Used During Perioperative Period for Major Surgery Platelet	0 Major surgeries	—
Type of Blood Component Transfusions Used During Perioperative Period for Major Surgery Fresh Frozen Plasma	0 Major surgeries	—
Type of Blood Component Transfusions Used During Perioperative Period for Major Surgery Whole Blood	0 Major surgeries	—
Type of Blood Component Transfusions Used During Perioperative Period for Major Surgery Other	0 Major surgeries	—

SECONDARY outcome

Timeframe: Day -1 to Day 0 (day of surgery)

Population: Analysis was performed on surgery subgroup population. Here, 'overall number of participants analyzed' = participants with major surgeries during the specified period and 'overall number of units analyzed' = number of major surgeries for which a loading dose was given on the day of surgery or one day prior to surgery (i.e. Day -1). As pre-specified, this outcome measure was planned to be analyzed combinedly for both the cohorts and presented under a single reporting group.

Perioperative period was time lapse surrounding surgical act which was divided into 3 stages: preoperative (4 weeks prior to surgery), operative (during surgery) and post-operative (24-hour post-surgery). Total dose (IU/kg) was sum across all injections per major surgery (including loading dose) needed to maintain hemostasis (process to prevent and stop bleeding from blood vessel) during surgery. Major surgery: defined as any invasive operative procedure that required any of the following: opening into major body cavity (e.g., abdomen, thorax, skull); operation on joint; removal of organ; dental extraction of any molar teeth or >=3 non-molar teeth; operative alteration of normal anatomy; crossing of mesenchymal barrier (e.g., pleura, peritoneum, dura). Day 0=surgery day. Loading dose for given surgery was preoperative injection, administered either on day of surgery or one day prior to surgery (i.e., Day -1).

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=2 Number of major surgeries Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Total Dose Required to Maintain Hemostasis From Day -1 to Day 0 During Perioperative Period for Major Surgery	61.13 IU/kg Standard Deviation 1.06	—

SECONDARY outcome

Timeframe: Day 0 (i.e., day of surgery)

Population: Analysis was performed on surgery subgroup population. Here, 'overall number of participants analyzed' = participants with reported blood loss during major surgery and 'overall number of units analyzed' = number of major surgeries with blood loss report during the treatment regimen occurred in participants analyzed. As pre-specified, this outcome measure was planned to be analyzed combinedly for both the cohorts and presented under a single reporting group.

The estimated total blood loss (in milliliters) during major surgeries were summarized. Major surgery: defined as any invasive operative procedure that required any of the following: opening into major body cavity (e.g., abdomen, thorax, skull); operation on a joint; removal of an organ; dental extraction of any molar teeth or >=3 non-molar teeth; operative alteration of normal anatomy; crossing of a mesenchymal barrier (e.g., pleura, peritoneum, dura).

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=2 Number of major surgery with blood loss Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Estimated Blood Loss During Major Surgery	25.00 milliliters Standard Deviation 35.36	—

SECONDARY outcome

Timeframe: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55)

Population: Analysis was performed on safety analysis set.

An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug which did not necessarily have a causal relationship with the treatment. A serious AE (SAE) was defined as any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability or incapacity, was a congenital anomaly or birth defect, or was a medically important event. Treatment-emergent AEs were AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=38 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=36 Participants Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse (TESAEs) TEAE	33 Participants	29 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse (TESAEs) TESAE	5 Participants	4 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Analysis was performed on safety analysis set.

Embolic and thrombotic events were defined as arterial or venous thrombosis, confirmed by imaging.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=38 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=36 Participants Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Number of Participants With Occurrence of Embolic and Thrombotic Events	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1

Population: Analysis was performed on PK population which included all participants who had completed adequate blood sample collection to assess key PK parameters. Data was planned to be collected and analyzed for combined population of both arm groups with the available PK data.

Cmax was defined as the maximum observed plasma FVIII Activity.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=37 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Pharmacokinetics (PK): Maximum FVIII Activity (Cmax)	128 IU per decilitre Standard Deviation 46.4	—

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1

Population: Analysis was performed on PK analysis set. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. Data was planned to be collected and analyzed for combined population of both arm groups with the available PK data.

CL is defined as the rate at which the drug is removed from the body.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=36 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Pharmacokinetics: Clearance (CL)	0.711 millilitres per hour per kilogram Standard Deviation 0.132	—

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1

Population: Analysis was performed on PK analysis set. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. Data was planned to be collected and analyzed for combined population of both arm groups with the available PK data.

Volume of distribution (Vd) is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss is the apparent volume of distribution at steady-state.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=36 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Pharmacokinetics: Volume of Distribution at Steady State (Vss)	37.3 milliliters per kilogram Standard Deviation 6.19	—

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1

Population: Analysis was performed on PK analysis set. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. Data was planned to be collected and analyzed for combined population of both arm groups with the available PK data.

Plasma t1/2z was the time measured for the plasma concentration of drug to decrease by one half.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=36 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Pharmacokinetics: Elimination Half-life (t1/2z)	40.2 hours Standard Deviation 4.29	—

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1

Population: Analysis was performed on PK analysis set. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. Data was planned to be collected and analyzed for combined population of both arm groups with the available PK data.

AUC0-tau was defined as area under the plasma concentration-time profile from time zero (pre-dose) to dosing interval.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=35 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Pharmacokinetics: Area Under the Plasma FVIII Activity Versus Time Curve (AUC0-tau)	7000 hour*IU per deciliter Standard Deviation 1300	—

SECONDARY outcome

Timeframe: 0 hour - 168 hour at week 26, 39 or 52

Population: Data for this outcome measure is not reported because samples were not collected to estimate CLss.

CLss is defined as the rate at which the drug is removed from the body at steady state.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1

Population: Analysis was performed on PK analysis set. Data was planned to be collected and analyzed for combined population of both arm groups with the available PK data.

IR was calculated as (Peak activity [in IU/dL] - Trough activity [in IU/dL])/Actual Dose (in IU/kg), and peak activity at each visit was the highest activity level after the dosing, and trough activity at each visit was the activity level prior to the dosing.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=37 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Pharmacokinetics: Incremental Recovery (IR)	2.53 IU/dL per IU/kg Standard Deviation 0.880	—

SECONDARY outcome

Timeframe: Pre-dose at Baseline (Day 1) and Week 52

Population: Analysis was performed on FAS population. Here, 'number analyzed' = participants with available data for each specified category. Data was planned to be collected and analyzed for combined population of both arm groups with the available PK data.

Ctrough is the pre-dose concentration of a drug. Ctrough was measured by apTT-Baseline-one-stage clotting assay.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=74 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Pharmacokinetics: Trough Concentration for BIVV001 (Ctrough) Baseline	0.00 IU/dL Standard Deviation 0.00	—
Pharmacokinetics: Trough Concentration for BIVV001 (Ctrough) Week 52	13.68 IU/dL Standard Deviation 21.84	—

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1

Population: Analysis was performed on PK analysis set. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. Data was planned to be collected and analyzed for combined population of both arm groups with the available PK data.

MRT is the average total time a drug molecule spends in the body.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=36 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Pharmacokinetics: Mean Residence Time (MRT)	53.0 hours Standard Deviation 6.22	—

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1

Population: Analysis was performed on PK analysis set. Here, 'number analyzed' = participants with available data for each specified category. Data was planned to be collected and analyzed for combined population of both arm groups with the available PK data.

Time above predefined (10% and 40%) FVIII activity levels mean time which BIVV001 maintains above 10 IU/dL and 40 IU/dL with single doses of 50 IU/kg.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=37 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Time Above Predefined (10% and 40%) FVIII Activity Levels Time to 10 IU/dL	160 hours Standard Deviation 18.7	—
Time Above Predefined (10% and 40%) FVIII Activity Levels Time to 40 IU/dL	72.2 hours Standard Deviation 12.5	—

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1

Population: Analysis was performed on PK analysis set. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. Data was planned to be collected and analyzed for combined population of both arm groups with the available PK data.

AUC0-tau was defined as the area under the activity-time curve over the dosing interval. AUC was normalized by dose.

Outcome measures

Measure	BIVV001: Participants Aged <6 Years n=35 Participants Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Pharmacokinetics: Dose-normalized Area Under the Activity-time Curve (DNAUC0-tau)	139 hour*kilogram*IU/deciliter/IU Standard Deviation 25.2	—

Adverse Events

BIVV001: Participants Aged <6 Years

Serious events: 5 serious events

Other events: 31 other events

Deaths: 0 deaths

BIVV001: Participants Aged 6 to <12 Years

Serious events: 4 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Measure	BIVV001: Participants Aged <6 Years n=38 participants at risk Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=36 participants at risk Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Infections and infestations Bacteraemia	2.6% 1/38 • Number of events 1 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	0.00% 0/36 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Infections and infestations Vascular Device Infection	5.3% 2/38 • Number of events 2 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	0.00% 0/36 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Metabolism and nutrition disorders Dehydration	2.6% 1/38 • Number of events 1 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	0.00% 0/36 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Respiratory, thoracic and mediastinal disorders Asthma	2.6% 1/38 • Number of events 1 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	0.00% 0/36 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Gastrointestinal disorders Eosinophilic Oesophagitis	0.00% 0/38 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	2.8% 1/36 • Number of events 1 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
General disorders Vascular Device Occlusion	0.00% 0/38 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	2.8% 1/36 • Number of events 1 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Injury, poisoning and procedural complications Head Injury	0.00% 0/38 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	2.8% 1/36 • Number of events 1 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Surgical and medical procedures Circumcision	2.6% 1/38 • Number of events 1 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	0.00% 0/36 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Product Issues Device Malfunction	0.00% 0/38 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	2.8% 1/36 • Number of events 1 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.

Other adverse events

Measure	BIVV001: Participants Aged <6 Years n=38 participants at risk Participants aged \<6 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.	BIVV001: Participants Aged 6 to <12 Years n=36 participants at risk Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Infections and infestations Asymptomatic Covid-19	5.3% 2/38 • Number of events 2 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	13.9% 5/36 • Number of events 5 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Infections and infestations Covid-19	2.6% 1/38 • Number of events 1 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	5.6% 2/36 • Number of events 2 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Infections and infestations Ear Infection	2.6% 1/38 • Number of events 1 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	5.6% 2/36 • Number of events 2 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Infections and infestations Gastroenteritis Viral	13.2% 5/38 • Number of events 6 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	2.8% 1/36 • Number of events 2 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Infections and infestations Influenza	0.00% 0/38 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	5.6% 2/36 • Number of events 2 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Infections and infestations Nasopharyngitis	7.9% 3/38 • Number of events 6 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	8.3% 3/36 • Number of events 3 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Infections and infestations Pharyngitis	0.00% 0/38 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	5.6% 2/36 • Number of events 2 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Infections and infestations Respiratory Tract Infection Viral	5.3% 2/38 • Number of events 3 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	0.00% 0/36 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Infections and infestations Upper Respiratory Tract Infection	15.8% 6/38 • Number of events 7 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	13.9% 5/36 • Number of events 7 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Infections and infestations Viral Infection	7.9% 3/38 • Number of events 4 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	2.8% 1/36 • Number of events 1 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Infections and infestations Viral Upper Respiratory Tract Infection	7.9% 3/38 • Number of events 4 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	2.8% 1/36 • Number of events 2 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Blood and lymphatic system disorders Iron Deficiency Anaemia	5.3% 2/38 • Number of events 2 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	0.00% 0/36 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Blood and lymphatic system disorders Neutropenia	7.9% 3/38 • Number of events 3 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	0.00% 0/36 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Immune system disorders Seasonal Allergy	2.6% 1/38 • Number of events 1 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	5.6% 2/36 • Number of events 2 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Nervous system disorders Headache	5.3% 2/38 • Number of events 2 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	2.8% 1/36 • Number of events 2 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Respiratory, thoracic and mediastinal disorders Cough	5.3% 2/38 • Number of events 2 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	2.8% 1/36 • Number of events 1 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	5.3% 2/38 • Number of events 5 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	0.00% 0/36 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Gastrointestinal disorders Constipation	2.6% 1/38 • Number of events 1 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	5.6% 2/36 • Number of events 2 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Gastrointestinal disorders Diarrhoea	7.9% 3/38 • Number of events 3 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	2.8% 1/36 • Number of events 1 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Gastrointestinal disorders Vomiting	10.5% 4/38 • Number of events 4 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	2.8% 1/36 • Number of events 1 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Skin and subcutaneous tissue disorders Eczema	7.9% 3/38 • Number of events 3 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	0.00% 0/36 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/38 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	13.9% 5/36 • Number of events 7 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Musculoskeletal and connective tissue disorders Pain In Extremity	5.3% 2/38 • Number of events 2 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	8.3% 3/36 • Number of events 4 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
General disorders Peripheral Swelling	5.3% 2/38 • Number of events 2 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	0.00% 0/36 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
General disorders Pyrexia	21.1% 8/38 • Number of events 17 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	2.8% 1/36 • Number of events 1 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Investigations Alanine Aminotransferase Increased	5.3% 2/38 • Number of events 2 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	0.00% 0/36 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Investigations Sars-Cov-2 Test Positive	18.4% 7/38 • Number of events 7 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	11.1% 4/36 • Number of events 6 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Injury, poisoning and procedural complications Contusion	2.6% 1/38 • Number of events 1 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	8.3% 3/36 • Number of events 3 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Injury, poisoning and procedural complications Head Injury	2.6% 1/38 • Number of events 1 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	11.1% 4/36 • Number of events 4 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Injury, poisoning and procedural complications Joint Injury	0.00% 0/38 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	5.6% 2/36 • Number of events 2 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.
Injury, poisoning and procedural complications Limb Injury	0.00% 0/38 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.	5.6% 2/36 • Number of events 3 • From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Analysis was performed on safety analysis set.

Additional Information

Trial Transparency Team

Bioverativ Therapeutics Inc. (a Sanofi Company)

Phone: 800-633-1610

Email: Contact-US@Sanofi.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
• Publication restrictions are in place

Restriction type: OTHER