A Phase 3 interventional study of efanesoctocog alfa (BIVV001) in Factor VIII Deficiency, sponsored by Bioverativ, a Sanofi company. Completed at 47 sites in 19 countries. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2025-09-17.
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 3rd largest by enrollment, is the only one that started in 2019, is one of 5 in phase 3, and was the 2nd 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: 12 Years and older · all sexes · 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. 1 started in 2019.
This study's enrollment of 159 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.
This tab as a report to print or save as PDF → With an account.
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 5th largest by enrollment of the 24 interventional ones that give a count, is one of 2 that started in 2019, is one of 14 in phase 3, and was the 18th 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:
This tab as a report to print or save as PDF → With an account.
Primary Objective:
- To evaluate the efficacy of BIVV001 as a prophylaxis treatment in prophylaxis treatment arm.
Secondary Objectives:
Participants in prophylaxis arm received a weekly prophylactic dose of BIVV001 for 52 weeks. Participants in on-demand arm received BIVV001 on demand for 26 weeks followed by a switch to weekly prophylaxis for another 26 weeks.
The Sponsor planned to perform a long-term safety trial. Enrollment in this open-label extension study would be offered to participants completing the treatment period based on eligibility criteria.
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.
Current regimen included one of the following:
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.
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
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.
Washout period
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
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 who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 international units per kilogram (IU/kg) intravenous (IV) injection once-weekly (QW) for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis \[OBS16221\]) in the outcome measure analysis.
Biological: efanesoctocog alfa (BIVV001)
Participants who were on an on-demand treatment regimen with a FVIII product prior to study EFC16293, including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection as an on-demand treatment (as needed for the treatment of bleeding episodes) from Week 1 to Week 26 in current study. At Week 26, participants in Arm B were switched to prophylaxis treatment, and received BIVV001 50 IU/kg, IV injection QW until Week 52.
Biological: efanesoctocog alfa (BIVV001)
Pharmaceutical form: solution for injection Route of administration: IV injection
Estimated Annualized Bleeding Rate (ABR) in Arm A: Prophylaxis
ABR is annualized number of treated bleeding episodes (BE) per participant per year. Treated Bleeding episode: 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 bleeding episode, any subsequent bleeding at same location/injections administered less than or equal to (\<=) 72 hours apart from previous injection were considered same bleeding episode. ABR=number of treated BE during efficacy period (EP)/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. This outcome measure (OM) presents estimated results (i.e., results estimated by fitting negative binomial \[NB\] regression model on data collected during EP).
Time frame: Baseline to Week 52
Observed Annualized Bleeding Rate in Arm A: Prophylaxis
ABR is annualized number of treated bleeding episodes per participant per year. Treated Bleeding episode: 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 bleeding episode, any subsequent bleeding at same location/injections administered \<=72 hours apart from previous injection were considered same bleeding episode. ABR=number of treated bleeding episodes during EP/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. This OM presents observed results (i.e., descriptive statistics values based on the data which was collected during EP).
Time frame: Baseline to Week 52
Estimated Annualized Bleeding Rate During the Efficacy Period in Arm A: Prophylaxis - Non-inferiority Analysis
ABR is annualized number of treated bleeding episodes per participant per year. Treated Bleeding episode: 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 bleeding episode, any subsequent bleeding at same location/injections administered \<=72 hours apart from previous injection were considered same bleeding episode. ABR=number of treated bleeding episodes during EP/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. This OM presents estimated results (i.e., results received estimated by fitting NB regression model on data collected during EP).
Time frame: Historical prophylaxis: From 6 months (prior to entry into study EFC16293) until the day before enrollment in EFC16293; BIVV001 prophylaxis: Baseline up to Week 52 of current study EFC16293
Observed Annualized Bleeding Rate During the Efficacy Period in Prophylaxis - Non-inferiority Analysis
ABR is annualized number of treated bleeding episodes per participant per year. Treated Bleeding episode: 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 bleeding episode, any subsequent bleeding at same location/injections administered \<=72 hours apart from previous injection were considered same bleeding episode. ABR=number of treated bleeding episodes during EP/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. This OM presents observed results (i.e., descriptive statistics values based on the data which was collected during EP).
Time frame: Historical prophylaxis: From 6 months (prior to entry into study EFC16293) until the day before enrollment in EFC16293; BIVV001 Prophylaxis: Baseline up to Week 52 of current study EFC16293
Estimated Annualized Bleeding Rate During the Efficacy Period in Arm A: Prophylaxis - Superiority Analysis
ABR is annualized number of treated bleeding episodes per participant per year. Treated Bleeding episode: 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 bleeding episode, any subsequent bleeding at same location/injections administered \<=72 hours apart from previous injection were considered same bleeding episode. ABR=number of treated bleeding episodes during EP/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. This OM presents estimated results (i.e., results received estimated by fitting NB regression model on data collected during EP).
Time frame: Historical Prophylaxis: From 6 months (prior to entry into study EFC16293) until the day before enrollment in EFC16293; BIVV001 Prophylaxis: Baseline up to Week 52 of current study EFC16293
Observed Annualized Bleeding Rate During the Efficacy Period in Arm A: Prophylaxis - Superiority Analysis
ABR is annualized number of treated bleeding episodes per participant per year. Treated Bleeding episode: 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 bleeding episode, any subsequent bleeding at same location/injections administered \<=72 hours apart from previous injection were considered same bleeding episode. ABR=number of treated bleeding episodes during EP/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. This OM presents observed results (i.e., descriptive statistics values based on the data which was collected during EP).
Time frame: Historical Prophylaxis: From 6 months (prior to entry into study EFC16293) until the day before enrollment in EFC16293; BIVV001 Prophylaxis: Baseline up to Week 52 of current study EFC16293
Change From Baseline in Hemophilia-specific Health-related Quality of Life Questionnaire for Adults (Haem-A-QOL) Physical Health Domain Score at Week 52 in Arm A: Prophylaxis
Haem-A-QoL is a participant-reported questionnaire designed for adult participants (greater than or equal to \[\>=\] 17 years of age) with hemophilia; and consisted of 46 items comprising 10 domains (physical health \[5 items\], feelings \[4 items\], view of self \[5 items\], sports and leisure \[5 items\], work and school \[4 items\], dealing with hemophilia \[3 items\], treatment \[8 items\], future \[5 items\], family planning \[4 items\], partnership and sexuality \[3 items\]). Items were rated along five response options: never, rarely, sometimes, often, or all the time. Raw score for physical health domain were transformed to a scale ranged from 0 to 100, where lower scores denoted better physical health. Change from baseline in physical Health domain score was reported in this OM.
Time frame: Baseline, Week 52
Change From Baseline in Patient Reported Outcomes Measurements Information Systems (PROMIS) Pain Intensity 3a Score at Week 52 in Arm A: Prophylaxis
PROMIS is a system of reliable and precise measures of participant-reported heath status. PROMIS measures cover physical, mental and social health and can be used for many chronic conditions. PROMIS - Pain Intensity - Short Form 3a consisted of 3 questions, participants reported for the intensity of pain experienced in the past 7 days. Each question had 5 responses scored between 1 (had no pain) to 5 (very severe pain). Total PROMIS pain intensity 3a score range was from 3 (no pain) to 15 (very severe pain), where higher score indicated more intense pain. Total raw score was converted into a T-score which rescaled raw score into standardized score with mean of 50 and standard deviation (SD) of 10. Higher PROMIS T-score represented worst outcome. For PROMIS pain intensity 3a, T-score of 60 was one SD worse than average.
Time frame: Baseline, Week 52
Change From Baseline in Hemophilia Joint Health Score (HJHS) Total Score at Week 52 in Arm A: Prophylaxis
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 and 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
Annualized Bleeding Rate by Type of Bleed (Spontaneous, Traumatic and Unknown Type)
ABR: annualized number of treated bleeding episodes per participant per year. EP 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 bleed at different location was considered as separate bleeding episode, regardless of time from last injection. Spontaneous bleeding: bleeding episode without contributing factor (definite trauma/antecedent "strenuous" activity). Traumatic bleeding: bleeding episode with known/believed reason for bleed.
Time frame: Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 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. 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 bleed at different location was considered as separate bleeding episode, regardless of time from last injection. Spontaneous bleeding: bleeding episode without contributing factor (definite trauma/antecedent "strenuous" activity). Traumatic bleeding: bleeding episode with known/believed reason for bleed.
Time frame: Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52
Annualized Bleeding Rate for All Bleeding Episodes
ABR: annualized number of all bleeding (treated and untreated) episodes/participant/year. ABR = number of all bleeding episodes during EP/number of days in EP\*365.25. EP reflects sum of all time intervals during which participants were treated with BIVV001 according to study arms and treatment regimens. Bleeding episode: episode 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 bleed at different location: considered as separate bleeding episode, regardless of time from last injection. Spontaneous: bleeding without contributing factor (definite trauma/antecedent "strenuous" activity). Traumatic: bleeding with known/believed reason.
Time frame: Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52
Annualized Bleeding Rate: Intra-participant Comparison of Arm B Participants
ABR is annualized number of treated bleeding episodes per participant per year. Treated Bleeding episode: 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 bleeding episode, any subsequent bleeding at same location/injections administered \<=72 hours apart from previous injection were considered same bleeding episode. ABR = (Number of treated bleeding episodes during EP/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: Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52
Percentage of Participants Achieving Factor VIII (FVIII) Activity Levels Above 1%, 5%, 10%, 15%, and 20% in Arm A: Prophylaxis
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%, 5%, 10%, 15%, and 20% were reported for Arm A: Prophylaxis in this OM. Participants were counted in more than one row, as applicable.
Time frame: Baseline to Week 52
Number of Injections of BIVV001 Required to Treat a Bleeding Episode
The number of injections required to resolve each bleeding episode was averaged across all bleeding episodes per participant. 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.
Time frame: Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52
Total Dose of BIVV001 Required to Treat Bleeding Episode
The total dose (IU/kg) used to resolve each bleeding episode was averaged across all bleeding episodes per participant. 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.
Time frame: Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 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. Percentage of bleeding episodes (of all bleeding episodes occurred) which were treated with single injection was reported in this OM.
Time frame: Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52
Percentage of Participants With Response to BIVV001 Treatment Based on the International Society on Thrombosis and Haemostasis (ISTH) 4-point Response Scale
The participant's response related to each injection of BIVV001 treatment for treating a bleed was evaluated using 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). Assessment was performed approximately 72 hours after the initial treatment for the bleeding episode. Bleeding episode was defined as an episode that started from first sign of a bleed and ended no more than 72 hours after last treatment for bleed, within which any symptoms of bleeding at same location or injections \<=72 hours apart were considered same bleeding episode. Participants were counted in more than one row, as applicable.
Time frame: Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52
Physicians' Global Assessment of Participant's Response to BIVV001 Treatment
Physicians assessed participant's response to BIVV001 treatment using 4-point response scale: Excellent=bleeding episodes (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. Percentages were based on total number of responses.
Time frame: Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 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: Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52
Change From Baseline in Hemophilia Joint Health Score (HJHS) Domain Score at Week 52 in Arm A: Prophylaxis
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), in each item 0 = none and higher score = severe damage.
Time frame: Baseline, Week 52
Estimated Annualized Joint Bleeding Rate (AJBR)
AJBR: annualized number of joint bleeding/participant/year. ABR = number of treated joint bleeding episodes during EP divided by total number of days during EP\*365.25. Joint bleeding episode: an unusual sensation in joint ('aura') in combination with 1) increasing swelling/warmth over skin, joint; 2) increasing pain or 3) progressive loss of range of motion or difficulty in using limb as compared with Baseline. Bleeding episode (BE): episode that started from first 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 bleeding episode. EP reflects the sum of all intervals of time during which participants were treated with BIVV001 according to study arms and treatment regimens.
Time frame: Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52
Observed Annualized Joint Bleeding Rate (AJBR)
AJBR: annualized number of joint bleeding/participant/year. ABR = number of treated joint bleeding episodes during EP divided by total number of days during EP\*365.25. Joint bleeding episode: unusual sensation in joint ('aura') with 1) in combination with increasing swelling/warmth over skin, joint; 2) increasing pain or 3) progressive loss of range of motion or difficulty in using limb as compared with Baseline. BE: episode that started from first 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 bleeding episode. EP reflects sum of all intervals of time during which participants were treated with BIVV001 according to study arms and treatment regimens.
Time frame: Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52
Total Number of Target Joint Resolved in Participants at Week 52 in Arm A: Prophylaxis
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. Total number of target joints resolved at Week 52 were reported.
Time frame: Week 52
Change From Baseline in Hemophilia-specific Health-related Quality of Life Questionnaire for Adults Total Score at Week 52 in Arm A: Prophylaxis
Haem-A-QoL: participant-reported questionnaire designed for adult participants (\>=17 years of age) with hemophilia; and consisted of 46 items comprising 10 domains (physical health \[5 items\], feelings \[4 items\], view of self \[5 items\], sports and leisure \[5 items\], work and school \[4 items\], dealing with hemophilia \[3 items\], treatment \[8 items\], future \[5 items\], family planning \[4 items\], partnership and sexuality \[3 items\]). Items were rated along 5 response options: 1=never, 2=rarely, 3=sometimes,4=often, and 5=all the time and higher scores represent greater impairment. Raw score for each domain were transformed to a scale ranged between 0 and 100, where lower scores denoted better physical health. Haem-A-QoL Total Score was average of all domain scores and ranged from 0 to 100, where lower scores = better quality of life.
Time frame: Baseline, Week 52
Change From Baseline in Patient Reported Outcomes Measurements Information Systems Short Form (PROMIS-SF) Physical Function (PF) 6b at Week 52 in Arm A: Prophylaxis
PROMIS-SF v2.0 PF 6b consisted of 2-items from item-improved Health Assessment Questionnaire (HAQ) and 4-items from item-improved Physical Function-10 (PF-10) instruments. Both of these instruments assessed participant's present abilities and had 5-response options: HAQ: 1=without any difficulty, 2=with little difficulty, 3=with some difficulty, 4=with much difficulty,5=unable to do and PF-10: 1=not at all, 2=very little, 3=somewhat, 4=quite a lot, 5=cannot do. Total score of PROMIS-SF PF 6b: average scores of component items, which ranged from 0 (no disability) to 100 (worst disability). T-score rescales raw scale score (sum of scores from all questions answered) into a standardized score with a mean of 50 and standard deviation of 10, based on scoring tables provided in PROMIS Scoring Manuals. Higher PROMIS T-score=more of concept being measured.
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 worst response: 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.
Time frame: Baseline 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 (a process to prevent and stop bleeding from a 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 the 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)
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 the surgery) and post-operative (24-hour post-surgery). Total dose (IU/kg) was the sum across all injections per major surgery (including loading dose) needed to maintain hemostasis (a process to prevent and stop bleeding from a 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 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). Day 0 was defined as the surgery day. The loading dose for a given surgery was the preoperative injection, administered either on the day of surgery or one day prior to the surgery (i.e., Day -1).
Time frame: Day -1 to Day 0 (day of surgery)
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 OM.
Time frame: Day -1 to Day 14
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)
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)
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 Events (TESAE)
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: Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 up to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55)
Number of Participants With Neutralizing Antibodies (Development of Inhibitors) Directed Against Factor VIII
Development of inhibitors was defined as an inhibitor result of \>=0.6 bethesda unit per milliliter (BU/mL) that was confirmed by a second test result of \>=0.6 BU/mL 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: Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52
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: Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52
Pharmacokinetics (PK): Maximum FVIII Activity (Cmax)
Cmax was defined as the maximum observed plasma FVIII Activity.
Time frame: Baseline (15 minutes post-dose on Day 1) and 15 minutes post-dose on Week 52
Pharmacokinetics: Elimination Half-life (t1/2z)
Plasma t1/2z was the time measured for the plasma concentration of drug to decrease by one half. Only for participants who were enrolled in sequential PK subgroup of study, PK samples were collected for all timepoints at Baseline and at Week 26; however, participants did not receive BIVV001 dose in week 2 and week 27.
Time frame: pre-dose, 0.25, 3, 24, 72, 168, 240 and 336 hours post-dose on Day 1 (Baseline); pre-dose, 0.25, 3, 24, 72, 168, 240, and 336 hours post-dose on Week 26
Pharmacokinetics: Clearance (CL)
CL is defined as the rate at which the drug is removed from the body. Only for participants who were enrolled in sequential PK subgroup of study, PK samples were collected for all timepoints at Baseline; however, participants did not receive BIVV001 dose in week 2 and week 27.
Time frame: Pre-dose, 0.25, 3, 24, 72, 168, 240 and 336 hours post-dose on Day 1 (Baseline)
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. Only for participants who were enrolled in sequential PK subgroup of study, PK samples were collected for all timepoints at Week 26; however, participants did not receive BIVV001 dose in week 2 and week 27.
Time frame: Pre-dose, 0.25, 3, 24, 72, 168, 240, and 336 hours post-dose on Week 26
Pharmacokinetics: Accumulation Index (AI)
AI is the ratio of accumulation of a drug under steady state conditions (i.e., after repeated administration) as compared to a single dose. AI was calculated as ratio of area under the curve (AUC) at Week 26 (Day 183) divided by AUC at Day 1, where AUC is the area under the plasma concentration versus time curve from time 0 to infinity. Only for participants who were enrolled in sequential PK subgroup of study, PK samples were collected for all timepoints at Week 26; however, participants did not receive BIVV001 dose in week 2 and week 27.
Time frame: Pre-dose, 0.25, 3, 24, 72, 168, 240, and 336 hours post-dose on Week 26
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. Only for participants who were enrolled in sequential PK subgroup of study, PK samples were collected for all timepoints at Baseline and at Week 26; however, participants did not receive BIVV001 dose in week 2 and week 27.
Time frame: Pre-dose, 0.25, 3, 24, 72, 168, 240 and 336 hours post-dose on Day 1 (Baseline); pre-dose, 0.25, 3, 24, 72, 168, 240, and 336 hours post-dose on Week 26 (Day 183)
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. Only for participants who were enrolled in sequential PK subgroup of study, PK samples were collected for all timepoints at Baseline and at Week 26; however, participants did not receive BIVV001 dose in week 2 and week 27.
Time frame: Pre-dose, 0.25, 3, 24, 72, 168, 240 and 336 hours post-dose on Day 1 (Baseline); pre-dose, 0.25, 3, 24, 72, 168, 240, and 336 hours post-dose on Week 26 (Day 183)
Pharmacokinetics: Mean Residence Time (MRT)
MRT is the average total time a drug molecule spends in the body. Only for participants who were enrolled in sequential PK subgroup of study, PK samples were collected for all timepoints at Baseline and at Week 26; however, participants did not receive BIVV001 dose in week 2 and week 27.
Time frame: Pre-dose, 0.25, 3, 24, 72, 168, 240 and 336 hours post-dose on Day 1 (Baseline); pre-dose, 0.25, 3, 24, 72, 168, 240, and 336 hours post-dose on Week 26 (Day 183)
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 hours post-dose on Day 1 (Baseline); pre-dose, 0.25 hours post-dose on Week 26 (Day 183)
Pharmacokinetics: Trough Concentration for BIVV001 (Ctrough)
Ctrough is the pre-dose concentration of a drug.
Time frame: Pre-dose at Baseline (Day 1) and Week 52
Pharmacokinetics: 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 dose of 50 IU/kg. Only for participants who were enrolled in sequential PK subgroup of study, PK samples were collected for all timepoints at Baseline; however, participants did not receive BIVV001 dose in week 2 and week 27.
Time frame: Pre-dose and 0.25, 3, 24, 72, 168, 240 and 336 hours post-dose on Day 1 (Baseline)
Study was conducted at 51 active sites in 19 countries. A total of 170 participants were screened between 19 November 2019 to 19 March 2021, of which 11 had screen failure due to not meeting the eligibility criteria.
| Milestone | Arm A: Prophylaxis | Arm B: On-Demand Then Prophylaxis |
|---|---|---|
| Started | 133 | 26 |
| Historical prophylaxis in obs16221 | 82 | 10 |
| Arm b: on-demand | 0 | 26 |
| Arm b: prophylaxis | 0 | 26 |
| Completed | 124 | 25 |
| Not completed | 9 | 1 |
| Withdrew: Withdrawal by subject | 3 | 0 |
| Withdrew: Protocol violation | 1 | 0 |
| Withdrew: Prohibited concomitant medication | 3 | 0 |
| Withdrew: Adverse event | 1 | 0 |
| Withdrew: Other - unspecified | 1 | 0 |
| Withdrew: Death | 0 | 1 |
ABR is annualized number of treated bleeding episodes (BE) per participant per year. Treated Bleeding episode: 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 bleeding episode, any subsequent bleeding at same location/injections administered less than or equal to (\<=) 72 hours apart from previous injection were considered same bleeding episode. ABR=number of treated BE during efficacy period (EP)/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. This outcome measure (OM) presents estimated results (i.e., results estimated by fitting negative binomial \[NB\] regression model on data collected during EP).
| episodes per participant per year | Arm A: Prophylaxis |
|---|---|
| Estimated Annualized Bleeding Rate (ABR) in Arm A: Prophylaxis | 0.71 (0.52 to 0.97) |
ABR is annualized number of treated bleeding episodes per participant per year. Treated Bleeding episode: 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 bleeding episode, any subsequent bleeding at same location/injections administered \<=72 hours apart from previous injection were considered same bleeding episode. ABR=number of treated bleeding episodes during EP/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. This OM presents observed results (i.e., descriptive statistics values based on the data which was collected during EP).
| episodes per participant per year | Arm A: Prophylaxis |
|---|---|
| Observed Annualized Bleeding Rate in Arm A: Prophylaxis | 0.71 ± 1.43 |
ABR is annualized number of treated bleeding episodes per participant per year. Treated Bleeding episode: 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 bleeding episode, any subsequent bleeding at same location/injections administered \<=72 hours apart from previous injection were considered same bleeding episode. ABR=number of treated bleeding episodes during EP/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. This OM presents estimated results (i.e., results received estimated by fitting NB regression model on data collected during EP).
| episodes per participant per year | Arm A: Historical Prophylaxis (OBS16221) | Arm A: BIVV001 Prophylaxis in EFC16293 |
|---|---|---|
| Estimated Annualized Bleeding Rate During the Efficacy Period in Arm A: Prophylaxis - Non-inferiority Analysis | 2.99 (2.03 to 4.42) | 0.69 (0.43 to 1.12) |
ABR is annualized number of treated bleeding episodes per participant per year. Treated Bleeding episode: 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 bleeding episode, any subsequent bleeding at same location/injections administered \<=72 hours apart from previous injection were considered same bleeding episode. ABR=number of treated bleeding episodes during EP/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. This OM presents observed results (i.e., descriptive statistics values based on the data which was collected during EP).
| episodes per participant per year | Arm A: Historical Prophylaxis (OBS16221) | Arm A: BIVV001 Prophylaxis in EFC16293 |
|---|---|---|
| Observed Annualized Bleeding Rate During the Efficacy Period in Prophylaxis - Non-inferiority Analysis | 2.98 ± 5.21 | 0.69 ± 1.51 |
ABR is annualized number of treated bleeding episodes per participant per year. Treated Bleeding episode: 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 bleeding episode, any subsequent bleeding at same location/injections administered \<=72 hours apart from previous injection were considered same bleeding episode. ABR=number of treated bleeding episodes during EP/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. This OM presents estimated results (i.e., results received estimated by fitting NB regression model on data collected during EP).
| episodes per participant per year | Arm A: Historical Prophylaxis (OBS16221) | Arm A: BIVV001 Prophylaxis in EFC16293 |
|---|---|---|
| Estimated Annualized Bleeding Rate During the Efficacy Period in Arm A: Prophylaxis - Superiority Analysis | 2.96 (2.00 to 4.37) | 0.69 (0.43 to 1.11) |
ABR is annualized number of treated bleeding episodes per participant per year. Treated Bleeding episode: 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 bleeding episode, any subsequent bleeding at same location/injections administered \<=72 hours apart from previous injection were considered same bleeding episode. ABR=number of treated bleeding episodes during EP/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. This OM presents observed results (i.e., descriptive statistics values based on the data which was collected during EP).
| episodes per participant per year | Arm A: Historical Prophylaxis (OBS16221) | Arm A: BIVV001 Prophylaxis in EFC16293 |
|---|---|---|
| Observed Annualized Bleeding Rate During the Efficacy Period in Arm A: Prophylaxis - Superiority Analysis | 2.95 ± 5.19 | 0.68 ± 1.50 |
Haem-A-QoL is a participant-reported questionnaire designed for adult participants (greater than or equal to \[\>=\] 17 years of age) with hemophilia; and consisted of 46 items comprising 10 domains (physical health \[5 items\], feelings \[4 items\], view of self \[5 items\], sports and leisure \[5 items\], work and school \[4 items\], dealing with hemophilia \[3 items\], treatment \[8 items\], future \[5 items\], family planning \[4 items\], partnership and sexuality \[3 items\]). Items were rated along five response options: never, rarely, sometimes, often, or all the time. Raw score for physical health domain were transformed to a scale ranged from 0 to 100, where lower scores denoted better physical health. Change from baseline in physical Health domain score was reported in this OM.
| score on a scale | Arm A: Prophylaxis |
|---|---|
| Change From Baseline in Hemophilia-specific Health-related Quality of Life Questionnaire for Adults (Haem-A-QOL) Physical Health Domain Score at Week 52 in Arm A: Prophylaxis | -6.79 ± 18.59 |
PROMIS is a system of reliable and precise measures of participant-reported heath status. PROMIS measures cover physical, mental and social health and can be used for many chronic conditions. PROMIS - Pain Intensity - Short Form 3a consisted of 3 questions, participants reported for the intensity of pain experienced in the past 7 days. Each question had 5 responses scored between 1 (had no pain) to 5 (very severe pain). Total PROMIS pain intensity 3a score range was from 3 (no pain) to 15 (very severe pain), where higher score indicated more intense pain. Total raw score was converted into a T-score which rescaled raw score into standardized score with mean of 50 and standard deviation (SD) of 10. Higher PROMIS T-score represented worst outcome. For PROMIS pain intensity 3a, T-score of 60 was one SD worse than average.
| T-score | Arm A: Prophylaxis |
|---|---|
| Change From Baseline in Patient Reported Outcomes Measurements Information Systems (PROMIS) Pain Intensity 3a Score at Week 52 in Arm A: Prophylaxis | -1.97 ± 7.86 |
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 and 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 | Arm A: Prophylaxis |
|---|---|
| Change From Baseline in Hemophilia Joint Health Score (HJHS) Total Score at Week 52 in Arm A: Prophylaxis | -1.5 ± 6.4 |
ABR: annualized number of treated bleeding episodes per participant per year. EP 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 bleed at different location was considered as separate bleeding episode, regardless of time from last injection. Spontaneous bleeding: bleeding episode without contributing factor (definite trauma/antecedent "strenuous" activity). Traumatic bleeding: bleeding episode with known/believed reason for bleed.
| episodes per participant per year | Arm A: Prophylaxis | Arm B: On-Demand | Arm B: Prophylaxis |
|---|---|---|---|
| Spontaneous | 0.00 (0.00 to 0.00) | 16.69 (8.64 to 23.76) | 0.00 (0.00 to 0.00) |
| Traumatic | 0.00 (0.00 to 0.00) | 3.95 (0.00 to 6.48) | 0.00 (0.00 to 0.00) |
| Unknown type | 0.00 (0.00 to 0.00) | 0.00 (0.00 to 0.00) | 0.00 (0.00 to 0.00) |
ABR: annualized number of treated bleeding episodes per participant per year. 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 bleed at different location was considered as separate bleeding episode, regardless of time from last injection. Spontaneous bleeding: bleeding episode without contributing factor (definite trauma/antecedent "strenuous" activity). Traumatic bleeding: bleeding episode with known/believed reason for bleed.
| episodes per participant per year | Arm A: Prophylaxis | Arm B: On-Demand | Arm B: Prophylaxis |
|---|---|---|---|
| Joint | 0.00 (0.00 to 1.02) | 18.42 (10.80 to 23.90) | 0.00 (0.00 to 0.00) |
| Muscle | 0.00 (0.00 to 0.00) | 0.00 (0.00 to 4.15) | 0.00 (0.00 to 0.00) |
| Internal | 0.00 (0.00 to 0.00) | 0.00 (0.00 to 0.00) | 0.00 (0.00 to 0.00) |
| Skin/mucosa | 0.00 (0.00 to 0.00) | 0.00 (0.00 to 2.09) | 0.00 (0.00 to 0.00) |
ABR: annualized number of all bleeding (treated and untreated) episodes/participant/year. ABR = number of all bleeding episodes during EP/number of days in EP\*365.25. EP reflects sum of all time intervals during which participants were treated with BIVV001 according to study arms and treatment regimens. Bleeding episode: episode 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 bleed at different location: considered as separate bleeding episode, regardless of time from last injection. Spontaneous: bleeding without contributing factor (definite trauma/antecedent "strenuous" activity). Traumatic: bleeding with known/believed reason.
| episodes per participant per year | Arm A: Prophylaxis | Arm B: On-Demand | Arm B: Prophylaxis |
|---|---|---|---|
| Annualized Bleeding Rate for All Bleeding Episodes | 0.00 (0.00 to 1.15) | 21.13 (16.80 to 27.13) | 0.00 (0.00 to 1.93) |
ABR is annualized number of treated bleeding episodes per participant per year. Treated Bleeding episode: 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 bleeding episode, any subsequent bleeding at same location/injections administered \<=72 hours apart from previous injection were considered same bleeding episode. ABR = (Number of treated bleeding episodes during EP/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.
| episodes per participant per year | Arm B: On-Demand | Arm B: Prophylaxis |
|---|---|---|
| Annualized Bleeding Rate: Intra-participant Comparison of Arm B Participants | 21.13 (15.12 to 27.13) | 0.00 (0.00 to 0.00) |
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%, 5%, 10%, 15%, and 20% were reported for Arm A: Prophylaxis in this OM. Participants were counted in more than one row, as applicable.
| percentage of participants | Arm A: Prophylaxis |
|---|---|
| >1% | 100 |
| >5% | 99.0 |
| >10% | 83.5 |
| >15% | 40.8 |
| >20% | 17.5 |
The number of injections required to resolve each bleeding episode was averaged across all bleeding episodes per participant. 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.
| injections per participant | Arm A: Prophylaxis | Arm B: On-Demand | Arm B: Prophylaxis |
|---|---|---|---|
| Number of Injections of BIVV001 Required to Treat a Bleeding Episode | 1.0 (1.0 to 1.0) | 1.0 (1.0 to 1.0) | 1.0 (1.0 to 1.0) |
The total dose (IU/kg) used to resolve each bleeding episode was averaged across all bleeding episodes per participant. 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.
| IU/kg | Arm A: Prophylaxis | Arm B: On-Demand | Arm B: Prophylaxis |
|---|---|---|---|
| Total Dose of BIVV001 Required to Treat Bleeding Episode | 50.85 (41.69 to 52.08) | 50.96 (50.10 to 51.83) | 49.79 (40.54 to 50.60) |
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. Percentage of bleeding episodes (of all bleeding episodes occurred) which were treated with single injection was reported in this OM.
| percentage of bleeding episodes | Arm A: Prophylaxis | Arm B: On-Demand | Arm B: Prophylaxis |
|---|---|---|---|
| Percentage of Bleeding Episodes Treated With a Single Injection of BIVV001 | 94.2 | 97.4 | 100 |
The participant's response related to each injection of BIVV001 treatment for treating a bleed was evaluated using 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). Assessment was performed approximately 72 hours after the initial treatment for the bleeding episode. Bleeding episode was defined as an episode that started from first sign of a bleed and ended no more than 72 hours after last treatment for bleed, within which any symptoms of bleeding at same location or injections \<=72 hours apart were considered same bleeding episode. Participants were counted in more than one row, as applicable.
| percentage of participants | Arm A: Prophylaxis | Arm B: On-Demand | Arm B: Prophylaxis |
|---|---|---|---|
| Excellent or Good | 82.2 | 98.4 | 100 |
| Excellent | 53.4 | 76.5 | 83.3 |
| Good | 28.8 | 22.0 | 16.7 |
| Moderate | 13.7 | 1.6 | 0 |
| None | 4.1 | 0 | 0 |
Physicians assessed participant's response to BIVV001 treatment using 4-point response scale: Excellent=bleeding episodes (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. Percentages were based on total number of responses.
| percentage of responses | Arm A: Prophylaxis | Arm B: On-Demand | Arm B: Prophylaxis |
|---|---|---|---|
| Excellent | 95.7 | 96.1 | 93.2 |
| Effective | 4.3 | 3.9 | 6.8 |
| Partially effective | 0 | 0 | 0 |
| Ineffective | 0 | 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 | Arm A: Prophylaxis | Arm B: On-Demand | Arm B: Prophylaxis |
|---|---|---|---|
| Total Annualized BIVV001 Consumption Per Participant | 2756.99 (2385.1 to 50171.7) | 1212.27 (435.9 to 2023.8) | 2737.53 (2486.4 to 2924.8) |
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), in each item 0 = none and higher score = severe damage.
| score on scale | Arm A: Prophylaxis |
|---|---|
| Swelling | -0.3 ± 1.2 |
| Duration Of Swelling | -0.2 ± 0.8 |
| Muscle Atrophy | -0.3 ± 1.2 |
| Crepitus On Motion | -0.3 ± 1.2 |
| Flexion Loss | -0.3 ± 1.6 |
| Extension Loss | -0.2 ± 1.5 |
| Joint Pain | -0.1 ± 1.2 |
| Strength | 0.3 ± 0.6 |
AJBR: annualized number of joint bleeding/participant/year. ABR = number of treated joint bleeding episodes during EP divided by total number of days during EP\*365.25. Joint bleeding episode: an unusual sensation in joint ('aura') in combination with 1) increasing swelling/warmth over skin, joint; 2) increasing pain or 3) progressive loss of range of motion or difficulty in using limb as compared with Baseline. Bleeding episode (BE): episode that started from first 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 bleeding episode. EP reflects the sum of all intervals of time during which participants were treated with BIVV001 according to study arms and treatment regimens.
| joint BE per participant per year | Arm A: Prophylaxis | Arm B: On-Demand | Arm B: Prophylaxis |
|---|---|---|---|
| Estimated Annualized Joint Bleeding Rate (AJBR) | 0.51 (0.36 to 0.72) | 17.48 (14.88 to 20.54) | 0.62 (0.25 to 1.52) |
AJBR: annualized number of joint bleeding/participant/year. ABR = number of treated joint bleeding episodes during EP divided by total number of days during EP\*365.25. Joint bleeding episode: unusual sensation in joint ('aura') with 1) in combination with increasing swelling/warmth over skin, joint; 2) increasing pain or 3) progressive loss of range of motion or difficulty in using limb as compared with Baseline. BE: episode that started from first 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 bleeding episode. EP reflects sum of all intervals of time during which participants were treated with BIVV001 according to study arms and treatment regimens.
| joint BE per participant per year | Arm A: Prophylaxis | Arm B: On-Demand | Arm B: Prophylaxis |
|---|---|---|---|
| Observed Annualized Joint Bleeding Rate (AJBR) | 0.52 ± 1.09 | 17.45 ± 7.31 | 0.61 ± 1.33 |
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. Total number of target joints resolved at Week 52 were reported.
| Target joints resolved | Arm A: Prophylaxis |
|---|---|
| Total Number of Target Joint Resolved in Participants at Week 52 in Arm A: Prophylaxis | 45 |
Haem-A-QoL: participant-reported questionnaire designed for adult participants (\>=17 years of age) with hemophilia; and consisted of 46 items comprising 10 domains (physical health \[5 items\], feelings \[4 items\], view of self \[5 items\], sports and leisure \[5 items\], work and school \[4 items\], dealing with hemophilia \[3 items\], treatment \[8 items\], future \[5 items\], family planning \[4 items\], partnership and sexuality \[3 items\]). Items were rated along 5 response options: 1=never, 2=rarely, 3=sometimes,4=often, and 5=all the time and higher scores represent greater impairment. Raw score for each domain were transformed to a scale ranged between 0 and 100, where lower scores denoted better physical health. Haem-A-QoL Total Score was average of all domain scores and ranged from 0 to 100, where lower scores = better quality of life.
| score on scale | Arm A: Prophylaxis |
|---|---|
| Change From Baseline in Hemophilia-specific Health-related Quality of Life Questionnaire for Adults Total Score at Week 52 in Arm A: Prophylaxis | -4.56 ± 11.15 |
PROMIS-SF v2.0 PF 6b consisted of 2-items from item-improved Health Assessment Questionnaire (HAQ) and 4-items from item-improved Physical Function-10 (PF-10) instruments. Both of these instruments assessed participant's present abilities and had 5-response options: HAQ: 1=without any difficulty, 2=with little difficulty, 3=with some difficulty, 4=with much difficulty,5=unable to do and PF-10: 1=not at all, 2=very little, 3=somewhat, 4=quite a lot, 5=cannot do. Total score of PROMIS-SF PF 6b: average scores of component items, which ranged from 0 (no disability) to 100 (worst disability). T-score rescales raw scale score (sum of scores from all questions answered) into a standardized score with a mean of 50 and standard deviation of 10, based on scoring tables provided in PROMIS Scoring Manuals. Higher PROMIS T-score=more of concept being measured.
| T-score | Arm A: Prophylaxis |
|---|---|
| Change From Baseline in Patient Reported Outcomes Measurements Information Systems Short Form (PROMIS-SF) Physical Function (PF) 6b at Week 52 in Arm A: Prophylaxis | 0.62 ± 4.77 |
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 worst response: 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.
| major surgeries | Participants With Major Surgery |
|---|---|
| Excellent or Good | 12 |
| Excellent | 12 |
| 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 (a process to prevent and stop bleeding from a 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 the 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).
| injections | Participants With Major Surgery |
|---|---|
| Zero injection | 1 |
| One injection | 11 |
| Two injection | 0 |
| Three injection | 0 |
| Four injection | 0 |
| >Four injection | 0 |
Perioperative period was 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 dose (IU/kg) was the sum across all injections per major surgery (including loading dose) needed to maintain hemostasis (a process to prevent and stop bleeding from a 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 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). Day 0 was defined as the surgery day. The loading dose for a given surgery was the preoperative injection, administered either on the day of surgery or one day prior to the 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 | 41.65 ± 15.21 |
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 OM.
| IU/kg per major surgery | Participants With Major Surgery |
|---|---|
| Total BIVV001 Consumption From Day -1 to 14 During Perioperative Period for Major Surgery | 166.71 ± 72.48 |
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).
| transfusions per surgery | Participants With Major Surgery |
|---|---|
| Zero | 12 |
| One | 0 |
| Two | 0 |
| Three | 0 |
| >Three | 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 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).
| transfusions per surgery | Participants With Major Surgery |
|---|---|
| Red Blood Cell | 0 |
| Platelet | 0 |
| Fresh Frozen Plasma | 0 |
| Whole Blood | 0 |
| Other | 0 |
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 | 143.33 ± 189.38 |
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 | Arm A: Prophylaxis | Arm B: On-Demand | Arm B: Prophylaxis |
|---|---|---|---|
| TEAE | 108 | 12 | 8 |
| TESAE | 13 | 2 | 0 |
Development of inhibitors was defined as an inhibitor result of \>=0.6 bethesda unit per milliliter (BU/mL) that was confirmed by a second test result of \>=0.6 BU/mL 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 | Arm A: Prophylaxis | Arm B: On-Demand | Arm B: Prophylaxis |
|---|---|---|---|
| Number of Participants With Neutralizing Antibodies (Development of Inhibitors) Directed Against Factor VIII | 0 | 0 | 0 |
Embolic and thrombotic events were defined as arterial or venous thrombosis, confirmed by imaging.
| Participants | Arm A: Prophylaxis | Arm B: On-Demand | Arm B: Prophylaxis |
|---|---|---|---|
| Number of Participants With Occurrence of Embolic and Thrombotic Events | 0 | 0 | 0 |
Cmax was defined as the maximum observed plasma FVIII Activity.
| IU per deciliter | Arm A: Prophylaxis | Arm B: On-Demand Then Prophylaxis |
|---|---|---|
| Baseline | 125.05 ± 31.72 | 138.36 ± 48.66 |
| Week 52 | 144.72 ± 36.65 | 149.42 ± 29.63 |
Plasma t1/2z was the time measured for the plasma concentration of drug to decrease by one half. Only for participants who were enrolled in sequential PK subgroup of study, PK samples were collected for all timepoints at Baseline and at Week 26; however, participants did not receive BIVV001 dose in week 2 and week 27.
| hours | BIVV001 (Efanesoctocog Alfa) |
|---|---|
| Baseline | 46.5 (29.1 to 104) |
| Week 26 | 46.7 (29.4 to 63.5) |
CL is defined as the rate at which the drug is removed from the body. Only for participants who were enrolled in sequential PK subgroup of study, PK samples were collected for all timepoints at Baseline; however, participants did not receive BIVV001 dose in week 2 and week 27.
| milliliter per hour per kilogram | BIVV001 (Efanesoctocog Alfa) |
|---|---|
| Pharmacokinetics: Clearance (CL) | 0.508 ± 0.124 |
CLss is defined as the rate at which the drug is removed from the body at steady state. Only for participants who were enrolled in sequential PK subgroup of study, PK samples were collected for all timepoints at Week 26; however, participants did not receive BIVV001 dose in week 2 and week 27.
| milliliter per hour per kilogram | BIVV001 (Efanesoctocog Alfa) |
|---|---|
| Pharmacokinetics: Total Clearance at Steady State (CLss) | 0.449 ± 0.101 |
AI is the ratio of accumulation of a drug under steady state conditions (i.e., after repeated administration) as compared to a single dose. AI was calculated as ratio of area under the curve (AUC) at Week 26 (Day 183) divided by AUC at Day 1, where AUC is the area under the plasma concentration versus time curve from time 0 to infinity. Only for participants who were enrolled in sequential PK subgroup of study, PK samples were collected for all timepoints at Week 26; however, participants did not receive BIVV001 dose in week 2 and week 27.
| ratio | BIVV001 (Efanesoctocog Alfa) |
|---|---|
| Pharmacokinetics: Accumulation Index (AI) | 1.17 ± 0.160 |
AUC0-tau was defined as area under the plasma concentration-time profile from time zero (pre-dose) to dosing interval. Only for participants who were enrolled in sequential PK subgroup of study, PK samples were collected for all timepoints at Baseline and at Week 26; however, participants did not receive BIVV001 dose in week 2 and week 27.
| hour*IU/deciliter | BIVV001 (Efanesoctocog Alfa) |
|---|---|
| Baseline | 9600 ± 2010 |
| Week 26 | 11800 ± 2720 |
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. Only for participants who were enrolled in sequential PK subgroup of study, PK samples were collected for all timepoints at Baseline and at Week 26; however, participants did not receive BIVV001 dose in week 2 and week 27.
| milliliters per kilogram | BIVV001 (Efanesoctocog Alfa) |
|---|---|
| Baseline | 31.7 ± 7.44 |
| Week 26 | 29.6 ± 8.26 |
MRT is the average total time a drug molecule spends in the body. Only for participants who were enrolled in sequential PK subgroup of study, PK samples were collected for all timepoints at Baseline and at Week 26; however, participants did not receive BIVV001 dose in week 2 and week 27.
| hours | BIVV001 (Efanesoctocog Alfa) |
|---|---|
| Baseline | 61.9 (34.3 to 111) |
| Week 26 | 66.1 (46.7 to 92.3) |
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) |
|---|---|
| Baseline | 2.60 ± 0.648 |
| Week 26 | 3.05 ± 0.592 |
Ctrough is the pre-dose concentration of a drug.
| IU/dL | Arm A: Prophylaxis | Arm B: On-Demand Then Prophylaxis |
|---|---|---|
| Baseline | 0.00 ± 0.00 | 0.00 ± 0.00 |
| Week 52 | 15.70 ± 10.72 | 21.14 ± 29.59 |
Time above predefined (10 and 40%) FVIII activity levels mean time which BIVV001 maintains above 10 IU/dL and 40 IU/dL with single dose of 50 IU/kg. Only for participants who were enrolled in sequential PK subgroup of study, PK samples were collected for all timepoints at Baseline; however, participants did not receive BIVV001 dose in week 2 and week 27.
| hours | BIVV001 (Efanesoctocog Alfa) |
|---|---|
| Time to 10 IU/dL | 185 (111 to 330) |
| Time to 40 IU/dL | 85.1 (44.4 to 156) |
Collected over Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: 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 |
|---|---|---|---|
| Arm A: Prophylaxis | 0/133 (0%) | 13/133 (9.8%) | 56/133 (42.1%) |
| Arm B: On-demand | 1/26 (3.8%) | 2/26 (7.7%) | 7/26 (26.9%) |
| Arm B: Prophylaxis | 0/26 (0%) | 0/26 (0%) | 1/26 (3.8%) |
| BIVV001 (Efanesoctocog Alfa): All Participants | 1/159 (0.6%) | 15/159 (9.4%) | 64/159 (40.3%) |
| Event | Arm A: Prophylaxis | Arm B: On-demand | Arm B: Prophylaxis | BIVV001 (Efanesoctocog Alfa): All Participants |
|---|---|---|---|---|
| Covid-19 PneumoniaInfections and infestations | 0/133 | 1/26 | 0/26 | 1/159 |
| Pancreatic Carcinoma MetastaticNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/133 | 1/26 | 0/26 | 1/159 |
| Haemophilic ArthropathyMusculoskeletal and connective tissue disorders | 2/133 | 0/26 | 0/26 | 2/159 |
| Basal Cell CarcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/133 | 0/26 | 0/26 | 1/159 |
| Cubital Tunnel SyndromeNervous system disorders | 1/133 | 0/26 | 0/26 | 1/159 |
| Status EpilepticusNervous system disorders | 1/133 | 0/26 | 0/26 | 1/159 |
| Ulnar Tunnel SyndromeNervous system disorders | 1/133 | 0/26 | 0/26 | 1/159 |
| Angina PectorisCardiac disorders | 1/133 | 0/26 | 0/26 | 1/159 |
| ArthropathyMusculoskeletal and connective tissue disorders | 1/133 | 0/26 | 0/26 | 1/159 |
| Mobility DecreasedMusculoskeletal and connective tissue disorders | 1/133 | 0/26 | 0/26 | 1/159 |
| Event | Arm A: Prophylaxis | Arm B: On-demand | Arm B: Prophylaxis | BIVV001 (Efanesoctocog Alfa): All Participants |
|---|---|---|---|---|
| HeadacheNervous system disorders | 26/133 | 5/26 | 1/26 | 32/159 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 25/133 | 1/26 | 0/26 | 26/159 |
| FallInjury, poisoning and procedural complications | 10/133 | 0/26 | 0/26 | 10/159 |
| Back PainMusculoskeletal and connective tissue disorders | 8/133 | 1/26 | 0/26 | 9/159 |
| FatigueGeneral disorders | 7/133 | 0/26 | 0/26 | 7/159 |
| Age, Continuous(years) | Arm A: Prophylaxis | Arm B: On-Demand Then Prophylaxis | Total Title |
|---|---|---|---|
| Mean | 33.9 ± 15.3 | 42.8 ± 11.7 | 35.4 ± 15.1 |
| Sex: Female, Male(Participants) | Arm A: Prophylaxis | Arm B: On-Demand Then Prophylaxis | Total Title |
|---|---|---|---|
| Female | 1 | 0 | 1 |
| Male | 132 | 26 | 158 |
| Race (NIH/OMB)(Participants) | Arm A: Prophylaxis | Arm B: On-Demand Then Prophylaxis | Total Title |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 29 | 0 | 29 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 3 | 0 | 3 |
| White | 71 | 26 | 97 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 30 | 0 | 30 |
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 Nov 2019 to primary completion in Feb 2022, 26 months.
Results were first posted in May 2023, 1 year 3 months 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 26 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 →