Trial · NCT04161495

A Phase 3 Open-label Interventional Study of Intravenous Recombinant Coagulation Factor VIII Fc-von Willebrand Factor-XTEN Fusion Protein, Efanesoctocog Alfa (BIVV001), in Patients With Severe Hemophilia A

NCT04161495, Phase 3, Completed, Bioverativ, a Sanofi company; results first posted 2023-05-24

3 sourcestrials-2026-11-12-0.5.0

Cite this record

ConductScience Library. A Phase 3 Open-label Interventional Study of Intravenous Recombinant Coagulation Factor VIII Fc-von Willebrand Factor-XTEN Fusion Protein, Efanesoctocog Alfa (BIVV001), in Patients With Severe Hemophilia A. Trials, record NCT04161495. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT04161495

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Trial

As registered on ClinicalTrials.gov, in the graph's capture of the registry.

Title: A Phase 3 Open-label Interventional Study of Intravenous Recombinant Coagulation Factor VIII Fc-von Willebrand Factor-XTEN Fusion Protein, Efanesoctocog Alfa (BIVV001), in Patients With Severe Hemophilia A
NCT number: NCT04161495
Status: Completed
Phases: Phase 3
Enrollment: 159 participants, actual
Lead sponsor: Bioverativ, a Sanofi company
Conditions: Factor VIII Deficiency
Interventions: efanesoctocog alfa (BIVV001)
First posted: 2019-11-13
Last updated: 2025-09-17
Other registries' IDs: eudract:2019-002023-15
Results first posted: 2023-05-24

Source ClinicalTrials.gov

Registered outcomes47

Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.

List	Outcome	Time frame	Description
Primary	Estimated Annualized Bleeding Rate (ABR) in Arm A: Prophylaxis	Baseline to Week 52	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).
Primary	Observed Annualized Bleeding Rate in Arm A: Prophylaxis	Baseline to Week 52	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).
Secondary	Estimated Annualized Bleeding Rate During the Efficacy Period in Arm A: Prophylaxis - Non-inferiority Analysis	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	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).
Secondary	Observed Annualized Bleeding Rate During the Efficacy Period in Prophylaxis - Non-inferiority Analysis	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	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).
Secondary	Estimated Annualized Bleeding Rate During the Efficacy Period in Arm A: Prophylaxis - Superiority Analysis	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	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).
Secondary	Observed Annualized Bleeding Rate During the Efficacy Period in Arm A: Prophylaxis - Superiority Analysis	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	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).
Secondary	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	Baseline, Week 52	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.
Secondary	Change From Baseline in Patient Reported Outcomes Measurements Information Systems (PROMIS) Pain Intensity 3a Score at Week 52 in Arm A: Prophylaxis	Baseline, Week 52	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.
Secondary	Change From Baseline in Hemophilia Joint Health Score (HJHS) Total Score at Week 52 in Arm A: Prophylaxis	Baseline, 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 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.
Secondary	Annualized Bleeding Rate by Type of Bleed (Spontaneous, Traumatic and Unknown Type)	Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52	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.

1 to 10 of 47Source ClinicalTrials.gov

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Outcomes47

Each outcome the trial posted results for, in ClinicalTrials.gov's words.

Type	Outcome	Time frame	Population	Units	Measured as
PRIMARY	Estimated Annualized Bleeding Rate (ABR) in Arm A: Prophylaxis	Baseline to Week 52	Analysis was performed on full analysis set (FAS) which included all participants who received at least 1 dose of study drug. Data for this OM was not planned to be collected and analyzed for Arm B.	episodes per participant per year	MEAN
PRIMARY	Observed Annualized Bleeding Rate in Arm A: Prophylaxis	Baseline to Week 52	Analysis was performed on FAS population. Data for this OM was not planned to be collected and analyzed for Arm B.	episodes per participant per year	MEAN
SECONDARY	Estimated Annualized Bleeding Rate During the Efficacy Period in Arm A: Prophylaxis - Non-inferiority Analysis	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	Analysis was performed on per protocol set which included all participants who had received at least one dose of study drug and did not had important protocol deviations potentially impacting efficacy. Data for this OM was not planned to be collected and analyzed for Arm B.	episodes per participant per year	MEAN
SECONDARY	Observed Annualized Bleeding Rate During the Efficacy Period in Prophylaxis - Non-inferiority Analysis	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	Analysis was performed on per protocol set. Data for this OM was not planned to be collected and analyzed for Arm B.	episodes per participant per year	MEAN
SECONDARY	Estimated Annualized Bleeding Rate During the Efficacy Period in Arm A: Prophylaxis - Superiority Analysis	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	Analysis was performed on FAS population. Data for this OM was not planned to be collected and analyzed for Arm B.	episodes per participant per year	MEAN
SECONDARY	Observed Annualized Bleeding Rate During the Efficacy Period in Arm A: Prophylaxis - Superiority Analysis	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	Analysis was performed on FAS population. Data for this OM was not planned to be collected and analyzed for Arm B.	episodes per participant per year	MEAN
SECONDARY	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	Baseline, Week 52	Analysis was performed on FAS population. Here, 'overall number of participants analyzed' = participants with available data for this OM. Data for this OM was not planned to be collected and analyzed for Arm B.	score on a scale	MEAN
SECONDARY	Change From Baseline in Patient Reported Outcomes Measurements Information Systems (PROMIS) Pain Intensity 3a Score at Week 52 in Arm A: Prophylaxis	Baseline, Week 52	Analysis was performed on FAS population. Here, 'overall number of participants analyzed' = participants with available data for this OM. Data for this OM was not planned to be collected and analyzed for Arm B.	T-score	MEAN
SECONDARY	Change From Baseline in Hemophilia Joint Health Score (HJHS) Total Score at Week 52 in Arm A: Prophylaxis	Baseline, Week 52	Analysis was performed on FAS population. Here, 'overall number of participants analyzed' = participants with available data for this OM. Data for this OM was not planned to be collected and analyzed for Arm B.	score on a scale	MEAN
SECONDARY	Annualized Bleeding Rate by Type of Bleed (Spontaneous, Traumatic and Unknown Type)	Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52	Analysis was performed on FAS. Data for this OM was planned to be collected and analyzed separately in Arm B for participants during on-demand treatment and during prophylaxis treatment post switch.	episodes per participant per year	MEDIAN

1 to 10 of 47Source ClinicalTrials.gov

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Results by group159

Each measurement the trial posted, group by group, in the words and numbers it posted.

Outcome	Group	Value	Spread	Units
Estimated Annualized Bleeding Rate (ABR) in Arm A: Prophylaxis	Arm A: Prophylaxis	0.71	95% Confidence Interval 0.52 to 0.97	episodes per participant per year
Observed Annualized Bleeding Rate in Arm A: Prophylaxis	Arm A: Prophylaxis	0.71	Standard Deviation 1.43	episodes per participant per year
Estimated Annualized Bleeding Rate During the Efficacy Period in Arm A: Prophylaxis - Non-inferiority Analysis	Arm A: Historical Prophylaxis (OBS16221)	2.99	95% Confidence Interval 2.03 to 4.42	episodes per participant per year
Estimated Annualized Bleeding Rate During the Efficacy Period in Arm A: Prophylaxis - Non-inferiority Analysis	Arm A: BIVV001 Prophylaxis in EFC16293	0.69	95% Confidence Interval 0.43 to 1.12	episodes per participant per year
Observed Annualized Bleeding Rate During the Efficacy Period in Prophylaxis - Non-inferiority Analysis	Arm A: Historical Prophylaxis (OBS16221)	2.98	Standard Deviation 5.21	episodes per participant per year
Observed Annualized Bleeding Rate During the Efficacy Period in Prophylaxis - Non-inferiority Analysis	Arm A: BIVV001 Prophylaxis in EFC16293	0.69	Standard Deviation 1.51	episodes per participant per year
Estimated Annualized Bleeding Rate During the Efficacy Period in Arm A: Prophylaxis - Superiority Analysis	Arm A: Historical Prophylaxis (OBS16221)	2.96	95% Confidence Interval 2.00 to 4.37	episodes per participant per year
Estimated Annualized Bleeding Rate During the Efficacy Period in Arm A: Prophylaxis - Superiority Analysis	Arm A: BIVV001 Prophylaxis in EFC16293	0.69	95% Confidence Interval 0.43 to 1.11	episodes per participant per year
Observed Annualized Bleeding Rate During the Efficacy Period in Arm A: Prophylaxis - Superiority Analysis	Arm A: Historical Prophylaxis (OBS16221)	2.95	Standard Deviation 5.19	episodes per participant per year
Observed Annualized Bleeding Rate During the Efficacy Period in Arm A: Prophylaxis - Superiority Analysis	Arm A: BIVV001 Prophylaxis in EFC16293	0.68	Standard Deviation 1.50	episodes per participant per year

1 to 10 of 159Source ClinicalTrials.gov

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Participant flow12

How many started, completed or left each group, period by period.

Period	Milestone	Group	Participants
Overall Study	STARTED	Arm A: Prophylaxis	133
Overall Study	STARTED	Arm B: On-Demand Then Prophylaxis	26
Overall Study	Historical Prophylaxis in OBS16221	Arm A: Prophylaxis	82
Overall Study	Historical Prophylaxis in OBS16221	Arm B: On-Demand Then Prophylaxis	10
Overall Study	Arm B: On-demand	Arm A: Prophylaxis	0
Overall Study	Arm B: On-demand	Arm B: On-Demand Then Prophylaxis	26
Overall Study	Arm B: Prophylaxis	Arm A: Prophylaxis	0
Overall Study	Arm B: Prophylaxis	Arm B: On-Demand Then Prophylaxis	26
Overall Study	COMPLETED	Arm A: Prophylaxis	124
Overall Study	COMPLETED	Arm B: On-Demand Then Prophylaxis	25

1 to 10 of 12Source ClinicalTrials.gov

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Adverse events84

Each adverse event the trial posted, group by group: the participants affected out of those at risk.

Type	Event	Organ system	Group	Affected	At risk	Events
other	Headache	Nervous system disorders	Arm A: Prophylaxis	26	133	40
other	Headache	Nervous system disorders	Arm B: On-demand	5	26	5
other	Headache	Nervous system disorders	Arm B: Prophylaxis	1	26	1
other	Headache	Nervous system disorders	BIVV001 (Efanesoctocog Alfa): All Participants	32	159	46
other	Arthralgia	Musculoskeletal and connective tissue disorders	Arm A: Prophylaxis	25	133	31
other	Arthralgia	Musculoskeletal and connective tissue disorders	Arm B: On-demand	1	26	1
other	Arthralgia	Musculoskeletal and connective tissue disorders	Arm B: Prophylaxis	0	26	0
other	Arthralgia	Musculoskeletal and connective tissue disorders	BIVV001 (Efanesoctocog Alfa): All Participants	26	159	32
other	Back Pain	Musculoskeletal and connective tissue disorders	Arm A: Prophylaxis	8	133	9
other	Back Pain	Musculoskeletal and connective tissue disorders	Arm B: On-demand	1	26	1

1 to 10 of 84Source ClinicalTrials.gov

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Adverse event totals12

The totals the trial posted for each group.

Total	Group	Affected	At risk
Total, all-cause mortality	Arm A: Prophylaxis	0	133
Total, all-cause mortality	Arm B: On-demand	1	26
Total, all-cause mortality	Arm B: Prophylaxis	0	26
Total, all-cause mortality	BIVV001 (Efanesoctocog Alfa): All Participants	1	159
Total, other adverse events	Arm A: Prophylaxis	56	133
Total, other adverse events	Arm B: On-demand	7	26
Total, other adverse events	Arm B: Prophylaxis	1	26
Total, other adverse events	BIVV001 (Efanesoctocog Alfa): All Participants	64	159
Total, serious adverse events	Arm A: Prophylaxis	13	133
Total, serious adverse events	Arm B: On-demand	2	26

1 to 10 of 12Source ClinicalTrials.gov

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Papers9

The papers the trial lists on ClinicalTrials.gov.

PMID	Listed as	Source
36720133	DERIVED	PubMed
39414418	DERIVED	PubMed
39576432	DERIVED	PubMed
39576433	DERIVED	PubMed
39927501	DERIVED	PubMed
40099428	DERIVED	PubMed
41583536	DERIVED	PubMed
41789959	DERIVED	PubMed
42598540	DERIVED	PubMed

Grants0

The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.

None in this release.

Trial comparisons0

Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.

None in this release.

Tests0

The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.

None in this release.

Data dates

The day each source was copied for this release.

ClinicalTrials.gov: 2026-11-12; ClinicalTrials.gov
Results, from AACT: 2026-03-23; AACT
NIH grant links: 2026-11-13; NIH RePORTER

Sources 3

ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
ClinicalTrials.govNo license stated
NIH RePORTER's clinical studies and project filesPublic domain

Each source's terms

ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
ClinicalTrials.govnone stated
NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)

ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.

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