A Phase 3 interventional study of efanesoctocog alfa (BIVV001) in Hemophilia A, sponsored by Bioverativ, a Sanofi company. Completed at 40 sites in 15 countries. Open to male participants aged Up to 11 Years. Per ClinicalTrials.gov, last updated 2025-09-11.
Sponsored by Bioverativ, a Sanofi company (part of Sanofi) · Phase 3, Interventional, and Treatment
Among 11 studies testing efanesoctocog alfa in Hemophilia A — 1 open to participants now, 5 under way, 2 of them phase 3. efanesoctocog alfa · Hemophilia A.
Among the 11 studies testing efanesoctocog alfa in Hemophilia A, this one is the 6th largest by enrollment, is one of 3 that started in 2021, is one of 5 in phase 3, and was the 4th registered.
844 studies on the registry are indexed under Hemophilia A; 136 are open to participants now.
Browse Hemophilia A studies →1 of the 11 studies testing efanesoctocog alfa in Hemophilia A is open now, in 5 countries. Recruiting first, the newest first:
Sanofi · Sites in United States, Australia, Canada and 2 more countries
Ages 12+
By country, each count listing its studies:
efanesoctocog alfa: first FDA approval 2023 (ALTUVIIIO), first EMA approval 2024. What it is approved for, and how studies give it, is on its page →
Of the 86 Hemophilia A studies recruiting now, 51 (59%) set no upper age limit and 30 (35%) stop at 75 or younger; 54 take children under 18; 10 take healthy volunteers.
This study: Up to 11 Years · male · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
11 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 1 3 · Phase 2 1 · Phase 3 5 · Phase 4 3
First in 2017; this study’s year is marked. 3 started in 2021.
This study's enrollment of 74 is above the median of 30 across 499 interventional studies indexed under Hemophilia A.
Median enrollment 74 across the 11 interventional studies. Of the 6 that completed or were terminated, 3 (50%) have results posted.
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11 of 11 have an industry lead sponsor. The 3 most frequent:
This study is registered under Bioverativ, a Sanofi company, one of the names counted as Sanofi. Under that name alone:
Bioverativ, a Sanofi company is the lead sponsor of 16 studies on the registry; none are open to participants now.
Of its 12 completed or terminated interventional studies of FDA-regulated products, 7 (58%) have results posted.
29 studies in Hemophilia A by Sanofi: 4 open now, 8 under way, 3 of them phase 3. Of 21 finished, 14 (67%) have results posted.
Among the 29 studies in Hemophilia A by Sanofi, this one is the 11th largest by enrollment of the 24 interventional ones that give a count, is one of 3 that started in 2021, is one of 14 in phase 3, and was the 20th registered.
Sanofi’s Hemophilia A studies by the year they started, since 2009.
4 of the studies testing efanesoctocog alfa in Hemophilia A that are under way reach primary completion within a year, 2 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT04644575Phase 3Bioverativ, a Sanofi companyLong-term Safety and Efficacy of Efanesoctocog Alfa (BIVV001) in Previously Treated Patients With Hemophilia A | 2027-01-15 |
| NCT06716814Phase 3Swedish Orphan BiovitrumStudy to Provide Continued Access to Treatment for Patients Completing a Previous Trial With Efanesoctocog Alfa | 2027-03 |
| NCT06752850Swedish Orphan BiovitrumA Study to Investigate the Course of Synovial Hypertrophy in Patients With Haemophilia A on Efanesoctocog Alfa Prophylaxis | 2026-11-17 |
| NCT06941870SanofiEfanesoctocog Alfa Prophylaxis in Patients With Hemophilia A With Synovial Hypertrophy | 2027-10-25 |
Add all 4 to your calendar (.ics) → With an account.
Among the 11 studies testing efanesoctocog alfa in Hemophilia A, from their registry updates:
Nothing recorded among them since 2026-09-25.
Among Sanofi’s 29 in Hemophilia A:
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Primary Objective:
- To evaluate the safety of BIVV001 in previously treated pediatric participants with hemophilia A.
Secondary Objectives:
Study duration per participants was approximately 60 weeks (maximum 8 weeks for screening and 52 weeks of treatment).
All participants completing or remaining at the end of study were offered participation in the planned extension trial.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion criteria:
The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants aged less than (\<) 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.
Drug: efanesoctocog alfa (BIVV001)
Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.
Drug: efanesoctocog alfa (BIVV001)
Pharmaceutical form: solution for injection Route of administration: IV
Number of Participants With Neutralising Antibodies (Development of Inhibitors) Directed Against Factor VIII
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.
Time frame: Baseline up to Week 52
Annualized Bleeding Rate (ABR): For Treated Bleeds
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.
Time frame: Baseline up to Week 52
Sensitivity Analysis: Annualized Bleeding Rate: For Treated Bleeds
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.
Time frame: Baseline up to Week 52
Annualized Bleeding Rate for All Bleeding Episodes
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.
Time frame: Baseline up to Week 52
Sensitivity Analysis: Annualized Bleeding Rate for All Bleeding Episodes
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.
Time frame: Baseline up to Week 52
Annualized Bleeding Rate by Type of Bleed (Spontaneous, Traumatic and Unknown Type)
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.
Time frame: Baseline up to Week 52
Sensitivity Analysis: Annualized Bleeding Rate by Type of Bleed (Spontaneous, Traumatic and Unknown Type)
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.
Time frame: Baseline up to Week 52
Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal and Skin/Mucosa)
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.
Time frame: Baseline up to Week 52
Sensitivity Analysis: Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal and Skin/Mucosa)
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.
Time frame: Baseline up to Week 52
Percentage of Participants Achieving FVIII Activity Levels Above 1%, 3%, 5%, 10%, 15%, and 20%
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.
Time frame: Baseline up to Week 52
Number of Injections of BIVV001 Required to Treat a Bleeding Episode
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.
Time frame: Baseline up to Week 52
Sensitivity Analysis: Number of Injections of BIVV001 Required to Treat a Bleeding Episode
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.
Time frame: Baseline up to Week 52
Percentage of Bleeding Episodes Treated With a Single Injection of BIVV001
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.
Time frame: Baseline up to Week 52
Sensitivity Analysis: Percentage of Bleeding Episodes Treated With a Single Injection of BIVV001
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.
Time frame: Baseline up to Week 52
Total Dose of BIVV001 Required to Treat a Bleeding Episode
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).
Time frame: Baseline up to Week 52
Sensitivity Analysis: Total Dose of BIVV001 Required to Treat a Bleeding Episode
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.
Time frame: Baseline up to Week 52
Physicians' Global Assessment (PGA) of Participant's Response to BIVV001 Treatment Based on a 4-point Response Scale
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.
Time frame: Week 13 and Week 52/End of study (EOS)/Early termination (ET)
Participant's Response to BIVV001 Treatment Based on the International Society on Thrombosis and Haemostasis (ISTH) 4-point Response Scale
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.
Time frame: Baseline up to Week 52
Total Annualized BIVV001 Consumption Per Participant
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.
Time frame: Baseline up to Week 52
Annualized Joint Bleeding Rate (AJBR)
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).
Time frame: Baseline up to Week 52
Sensitivity Analysis: Annualized Joint Bleeding Rate (AJBR)
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).
Time frame: Baseline up to Week 52
Change From Baseline in Hemophilia Joint Health Score Domain Score at Week 52
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.
Time frame: Baseline, Week 52
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)
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.
Time frame: Baseline, Week 52
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
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.
Time frame: Baseline, Week 52
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)
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.
Time frame: Baseline, Week 52
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
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.
Time frame: Baseline, Week 52
Total Number of Target Joints Resolved in Participants at Week 52
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.
Time frame: Week 52
Change From Baseline in Hemophilia Joint Health Score (HJHS) Total Score at Week 52
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.
Time frame: Baseline, Week 52
Investigators' or Surgeons' Assessment of Participant's Hemostatic Response to BIVV001 Treatment
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.
Time frame: Baseline up to Week 52
Number of Injections Per Surgery Required to Maintain Hemostasis During Perioperative Period for Major Surgery
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).
Time frame: During the perioperative period (any time during Baseline up to Week 52)
Number of Blood Component Transfusions Used During Perioperative Period for Major Surgery
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).
Time frame: During the perioperative period (any time during Baseline up to Week 52)
Total BIVV001 Consumption From Day -1 to 14 During Perioperative Period for Major Surgery
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.
Time frame: Day -1 to Day 14
Type of Blood Component Transfusions Used During Perioperative Period for Major Surgery
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).
Time frame: During the perioperative period (any time during Baseline up to Week 52)
Total Dose Required to Maintain Hemostasis From Day -1 to Day 0 During Perioperative Period for Major Surgery
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).
Time frame: Day -1 to Day 0 (day of surgery)
Estimated Blood Loss During Major Surgery
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).
Time frame: Day 0 (i.e., day of surgery)
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse (TESAEs)
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.
Time frame: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55)
Number of Participants With Occurrence of Embolic and Thrombotic Events
Embolic and thrombotic events were defined as arterial or venous thrombosis, confirmed by imaging.
Time frame: Baseline up to Week 52
Pharmacokinetics (PK): Maximum FVIII Activity (Cmax)
Cmax was defined as the maximum observed plasma FVIII Activity.
Time frame: Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1
Pharmacokinetics: Clearance (CL)
CL is defined as the rate at which the drug is removed from the body.
Time frame: Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1
Pharmacokinetics: Volume of Distribution at Steady State (Vss)
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.
Time frame: Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1
Pharmacokinetics: Elimination Half-life (t1/2z)
Plasma t1/2z was the time measured for the plasma concentration of drug to decrease by one half.
Time frame: Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1
Pharmacokinetics: Area Under the Plasma FVIII Activity Versus Time Curve (AUC0-tau)
AUC0-tau was defined as area under the plasma concentration-time profile from time zero (pre-dose) to dosing interval.
Time frame: Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1
Pharmacokinetics: Total Clearance at Steady State (CLss)
CLss is defined as the rate at which the drug is removed from the body at steady state.
Time frame: 0 hour - 168 hour at week 26, 39 or 52
Pharmacokinetics: Incremental Recovery (IR)
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.
Time frame: Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1
Pharmacokinetics: Trough Concentration for BIVV001 (Ctrough)
Ctrough is the pre-dose concentration of a drug. Ctrough was measured by apTT-Baseline-one-stage clotting assay.
Time frame: Pre-dose at Baseline (Day 1) and Week 52
Pharmacokinetics: Mean Residence Time (MRT)
MRT is the average total time a drug molecule spends in the body.
Time frame: Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1
Time Above Predefined (10% and 40%) FVIII Activity Levels
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.
Time frame: Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1
Pharmacokinetics: Dose-normalized Area Under the Activity-time Curve (DNAUC0-tau)
AUC0-tau was defined as the area under the activity-time curve over the dosing interval. AUC was normalized by dose.
Time frame: Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1
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.
| Milestone | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| Started | 38 | 36 |
| Completed | 36 | 36 |
| Not completed | 2 | 0 |
| Withdrew: Investigator's discretion | 1 | 0 |
| Withdrew: Subject withdrawal | 1 | 0 |
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.
| Participants | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| Number of Participants With Neutralising Antibodies (Development of Inhibitors) Directed Against Factor VIII | 0 | 0 |
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.
| episodes per participant per year | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| Annualized Bleeding Rate (ABR): For Treated Bleeds | 0.48 (0.30 to 0.77) | 1.33 (0.64 to 2.76) |
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.
| episodes per participant per year | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| Sensitivity Analysis: Annualized Bleeding Rate: For Treated Bleeds | 0.48 (0.30 to 0.77) | 0.75 (0.41 to 1.40) |
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.
| episodes per participant per year | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| Annualized Bleeding Rate for All Bleeding Episodes | 2.78 (1.39 to 5.58) | 2.85 (1.59 to 5.12) |
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.
| episodes per participant per year | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| Sensitivity Analysis: Annualized Bleeding Rate for All Bleeding Episodes | 2.78 (1.39 to 5.58) | 2.32 (1.30 to 4.13) |
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.
| episodes per participant per year | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| Spontaneous | 0.17 (0.08 to 0.38) | 0.14 (0.04 to 0.53) |
| Traumatic | 0.28 (0.14 to 0.55) | 0.59 (0.31 to 1.14) |
| Unknown type | 0.03 (0.00 to 0.20) | 0.59 (0.12 to 3.02) |
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.
| episodes per participant per year | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| Spontaneous | 0.17 (0.08 to 0.38) | 0.15 (0.04 to 0.55) |
| Traumatic | 0.28 (0.14 to 0.55) | 0.52 (0.26 to 1.04) |
| Unknown type | 0.03 (0.00 to 0.20) | 0.09 (0.03 to 0.27) |
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.
| episodes per participant per year | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| Joint | 0.19 ± 0.63 | 0.99 ± 3.62 |
| Muscle | 0.03 ± 0.16 | 0.17 ± 0.51 |
| Internal | 0.08 ± 0.28 | 0.06 ± 0.35 |
| Skin/mucosa | 0.16 ± 0.38 | 0.25 ± 0.60 |
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.
| episodes per participant per year | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| Joint | 0.19 ± 0.63 | 0.40 ± 0.93 |
| Muscle | 0.03 ± 0.16 | 0.17 ± 0.52 |
| Internal | 0.08 ± 0.28 | 0.06 ± 0.35 |
| Skin/mucosa | 0.16 ± 0.38 | 0.26 ± 0.61 |
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.
| percentage of participants | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| >1% | 100 | 100 |
| >3% | 100 | 100 |
| >5% | 75.0 | 100 |
| >10% | 18.8 | 51.7 |
| >15% | 9.4 | 6.9 |
| >20% | 3.1 | 6.9 |
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.
| injections per bleeding episode | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| Number of Injections of BIVV001 Required to Treat a Bleeding Episode | 1.12 ± 0.33 | 1.30 ± 0.69 |
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.
| injections per bleeding episode | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| Sensitivity Analysis: Number of Injections of BIVV001 Required to Treat a Bleeding Episode | 1.12 ± 0.33 | 1.00 ± 0.00 |
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.
| percentage of bleeding episodes | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| Percentage of Bleeding Episodes Treated With a Single Injection of BIVV001 | 88.2 | 78.7 |
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.
| percentage of bleeding episodes | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| Sensitivity Analysis: Percentage of Bleeding Episodes Treated With a Single Injection of BIVV001 | 88.2 | 100 |
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).
| IU/kg | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| Total Dose of BIVV001 Required to Treat a Bleeding Episode | 52.29 ± 15.84 | 66.90 ± 37.01 |
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.
| IU/kg | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| Sensitivity Analysis: Total Dose of BIVV001 Required to Treat a Bleeding Episode | 52.29 ± 15.84 | 50.39 ± 6.71 |
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.
| Participants | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| Week 13: Excellent | 37 | 34 |
| Week 13: Effective | 0 | 2 |
| Week 13: Partially effective | 0 | 0 |
| Week 13: Ineffective | 0 | 0 |
| Week 52/EOS/ET: Excellent | 37 | 36 |
| Week 52/EOS/ET: Effective | 0 | 0 |
| Week 52/EOS/ET: Partially effective | 0 | 0 |
| Week 52/EOS/ET: Ineffective | 0 | 0 |
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.
| Injections with a response | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| Excellent | 14 | 22 |
| Good | 1 | 2 |
| Moderate | 1 | 0 |
| None | 0 | 0 |
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.
| IU/kg per participant per year | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| Total Annualized BIVV001 Consumption Per Participant | 3115.57 ± 488.64 | 2884.67 ± 207.88 |
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).
| joint BE per participant per year | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| Annualized Joint Bleeding Rate (AJBR) | 0.19 (0.06 to 0.62) | 0.99 (0.38 to 2.60) |
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).
| joint BE per participant per year | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| Sensitivity Analysis: Annualized Joint Bleeding Rate (AJBR) | 0.19 (0.06 to 0.62) | 0.41 (0.19 to 0.89) |
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.
| score on a scale | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| Swelling | 0.0 ± 0.0 | -0.1 ± 0.6 |
| Duration Of Swelling | 0.1 ± 0.2 | -0.0 ± 0.2 |
| Muscle Atrophy | 0.0 ± 0.0 | -0.1 ± 0.4 |
| Crepitus On Motion | 0.1 ± 0.2 | -0.1 ± 0.5 |
| Flexion Loss | -0.9 ± 4.1 | -0.1 ± 0.6 |
| Extension Loss | -0.2 ± 1.0 | 0.2 ± 0.9 |
| Joint Pain | 0.0 ± 0.0 | 0.0 ± 0.4 |
| Strength | 1.3 ± 10.0 | -0.8 ± 4.2 |
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.
| score on a scale | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| 4 to 7 years | -5.31 ± 10.83 | 4.69 ± 5.41 |
| 8 to <12 years | — | -9.79 ± 12.18 |
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.
| score on a scale | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| 4 to 7 years | -3.21 ± 12.23 | -1.17 ± 11.08 |
| 8 to <12 years | — | -4.05 ± 10.77 |
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.
| score on a scale | BIVV001: Participants Aged 6 to <12 Years |
|---|---|
| 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 ± 14.75 |
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.
| score on a scale | BIVV001: Participants Aged 6 to <12 Years |
|---|---|
| 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 ± 11.60 |
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.
| Target joints resolved | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| Total Number of Target Joints Resolved in Participants at Week 52 | — | 2 |
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.
| score on a scale | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| Change From Baseline in Hemophilia Joint Health Score (HJHS) Total Score at Week 52 | 0.2 ± 8.3 | -1.1 ± 4.3 |
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.
| major surgeries | Participants With Major Surgery |
|---|---|
| Excellent or Good | 2 |
| Excellent | 2 |
| Good | 0 |
| Fair | 0 |
| Poor/none | 0 |
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).
| Major surgeries | Participants With Major Surgery |
|---|---|
| One injection | 2 |
| Two injection | 0 |
| Three injection | 0 |
| Four injection | 0 |
| >Four injection | 0 |
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).
| Major surgeries | Participants With Major Surgery |
|---|---|
| Zero | 2 |
| One | 0 |
| Two | 0 |
| Three | 0 |
| >Three | 0 |
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.
| IU/kg per major surgery | Participants With Major Surgery |
|---|---|
| Total BIVV001 Consumption From Day -1 to 14 During Perioperative Period for Major Surgery | 201.97 ± 29.42 |
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).
| Major surgeries | Participants With Major Surgery |
|---|---|
| Red Blood Cell | 0 |
| Platelet | 0 |
| Fresh Frozen Plasma | 0 |
| Whole Blood | 0 |
| Other | 0 |
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).
| IU/kg | Participants With Major Surgery |
|---|---|
| Total Dose Required to Maintain Hemostasis From Day -1 to Day 0 During Perioperative Period for Major Surgery | 61.13 ± 1.06 |
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).
| milliliters | Participants With Major Surgery |
|---|---|
| Estimated Blood Loss During Major Surgery | 25.00 ± 35.36 |
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.
| Participants | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| TEAE | 33 | 29 |
| TESAE | 5 | 4 |
Embolic and thrombotic events were defined as arterial or venous thrombosis, confirmed by imaging.
| Participants | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| Number of Participants With Occurrence of Embolic and Thrombotic Events | 0 | 0 |
Cmax was defined as the maximum observed plasma FVIII Activity.
| IU per decilitre | BIVV001 (Efanesoctocog Alfa) |
|---|---|
| Pharmacokinetics (PK): Maximum FVIII Activity (Cmax) | 128 ± 46.4 |
CL is defined as the rate at which the drug is removed from the body.
| millilitres per hour per kilogram | BIVV001 (Efanesoctocog Alfa) |
|---|---|
| Pharmacokinetics: Clearance (CL) | 0.711 ± 0.132 |
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.
| milliliters per kilogram | BIVV001 (Efanesoctocog Alfa) |
|---|---|
| Pharmacokinetics: Volume of Distribution at Steady State (Vss) | 37.3 ± 6.19 |
Plasma t1/2z was the time measured for the plasma concentration of drug to decrease by one half.
| hours | BIVV001 (Efanesoctocog Alfa) |
|---|---|
| Pharmacokinetics: Elimination Half-life (t1/2z) | 40.2 ± 4.29 |
AUC0-tau was defined as area under the plasma concentration-time profile from time zero (pre-dose) to dosing interval.
| hour*IU per deciliter | BIVV001 (Efanesoctocog Alfa) |
|---|---|
| Pharmacokinetics: Area Under the Plasma FVIII Activity Versus Time Curve (AUC0-tau) | 7000 ± 1300 |
CLss is defined as the rate at which the drug is removed from the body at steady state.
No measurements were reported for this outcome.
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.
| IU/dL per IU/kg | BIVV001 (Efanesoctocog Alfa) |
|---|---|
| Pharmacokinetics: Incremental Recovery (IR) | 2.53 ± 0.880 |
Ctrough is the pre-dose concentration of a drug. Ctrough was measured by apTT-Baseline-one-stage clotting assay.
| IU/dL | BIVV001 (Efanesoctocog Alfa) |
|---|---|
| Baseline | 0.00 ± 0.00 |
| Week 52 | 13.68 ± 21.84 |
MRT is the average total time a drug molecule spends in the body.
| hours | BIVV001 (Efanesoctocog Alfa) |
|---|---|
| Pharmacokinetics: Mean Residence Time (MRT) | 53.0 ± 6.22 |
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.
| hours | BIVV001 (Efanesoctocog Alfa) |
|---|---|
| Time to 10 IU/dL | 160 ± 18.7 |
| Time to 40 IU/dL | 72.2 ± 12.5 |
AUC0-tau was defined as the area under the activity-time curve over the dosing interval. AUC was normalized by dose.
| hour*kilogram*IU/deciliter/IU | BIVV001 (Efanesoctocog Alfa) |
|---|---|
| Pharmacokinetics: Dose-normalized Area Under the Activity-time Curve (DNAUC0-tau) | 139 ± 25.2 |
Collected over From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| BIVV001: Participants Aged <6 Years | 0/38 (0%) | 5/38 (13.2%) | 31/38 (81.6%) |
| BIVV001: Participants Aged 6 to <12 Years | 0/36 (0%) | 4/36 (11.1%) | 28/36 (77.8%) |
| Event | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| Vascular Device InfectionInfections and infestations | 2/38 | 0/36 |
| Eosinophilic OesophagitisGastrointestinal disorders | 0/38 | 1/36 |
| Vascular Device OcclusionGeneral disorders | 0/38 | 1/36 |
| Head InjuryInjury, poisoning and procedural complications | 0/38 | 1/36 |
| Device MalfunctionProduct Issues | 0/38 | 1/36 |
| BacteraemiaInfections and infestations | 1/38 | 0/36 |
| DehydrationMetabolism and nutrition disorders | 1/38 | 0/36 |
| AsthmaRespiratory, thoracic and mediastinal disorders | 1/38 | 0/36 |
| CircumcisionSurgical and medical procedures | 1/38 | 0/36 |
| Event | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years |
|---|---|---|
| PyrexiaGeneral disorders | 8/38 | 1/36 |
| Sars-Cov-2 Test PositiveInvestigations | 7/38 | 4/36 |
| Upper Respiratory Tract InfectionInfections and infestations | 6/38 | 5/36 |
| Asymptomatic Covid-19Infections and infestations | 2/38 | 5/36 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 0/38 | 5/36 |
| Gastroenteritis ViralInfections and infestations | 5/38 | 1/36 |
| Head InjuryInjury, poisoning and procedural complications | 1/38 | 4/36 |
| VomitingGastrointestinal disorders | 4/38 | 1/36 |
| NasopharyngitisInfections and infestations | 3/38 | 3/36 |
| Pain In ExtremityMusculoskeletal and connective tissue disorders | 2/38 | 3/36 |
Analysis was performed on full analysis set (FAS) which included all participants who took at least 1 dose of study intervention.
| Age, Continuous(years) | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years | Total |
|---|---|---|---|
| Mean | 3.69 ± 1.21 | 8.42 ± 2.08 | 5.99 ± 2.91 |
| Age, Customized(Participants) | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years | Total |
|---|---|---|---|
| Children (1 to 5 years) | 38 | 0 | 38 |
| Children (>=6 to 11 years) | 0 | 36 | 36 |
| Sex: Female, Male(Participants) | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years | Total |
|---|---|---|---|
| Female | 0 | 0 | 0 |
| Male | 38 | 36 | 74 |
| Race/Ethnicity, Customized(Participants) | BIVV001: Participants Aged <6 Years | BIVV001: Participants Aged 6 to <12 Years | Total |
|---|---|---|---|
| Race — Asian | 4 | 4 | 8 |
| Race — Black or African American | 1 | 2 | 3 |
| Race — White | 30 | 25 | 55 |
| Race — Other or Not Reported | 3 | 5 | 8 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Ran from Feb 2021 to primary completion in Jan 2023, 22 months.
Results were first posted in Feb 2024, 1 year after primary completion.
Of 89 industry-sponsored phase 3 interventional studies under Hemophilia A, half reached primary completion within 32 months of starting (the median), counting those still running; a quarter within 18 and three quarters within 56. This study's 22 months is below that.
Counting every sponsor, half of 91 studies reached it within 33 months; a quarter within 20 and three quarters within 56.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Sep 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Efanesoctocog alfa
Bioverativ, a Sanofi company →