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 ID: NCT04161495

Last Updated: 2025-09-17

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

159 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-11-19

Study Completion Date

2022-02-03

Brief Summary

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Primary Objective:

\- To evaluate the efficacy of BIVV001 as a prophylaxis treatment in prophylaxis treatment arm.

Secondary Objectives:

* To evaluate the efficacy of BIVV001 as a prophylaxis treatment.
* To evaluate the efficacy of BIVV001 in the treatment of bleeding episodes.
* To evaluate BIVV001 consumption for the prevention and treatment of bleeding episodes.
* To evaluate the effect of BIVV001 prophylaxis on joint health outcomes.
* To evaluate the effect of BIVV001 prophylaxis on Quality of Life outcomes.
* To evaluate the efficacy of BIVV001 for perioperative management.
* To evaluate the safety and tolerability of BIVV001 treatment.
* To assess the pharmacokinetics (PK) of BIVV001 based on the 1-stage activated partial thromboplastin time (aPTT) and 2-stage chromogenic coagulation factor VIII (FVIII) activity assays.

Detailed Description

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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.

Conditions

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Factor VIII Deficiency

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A: Prophylaxis

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.

Group Type EXPERIMENTAL

efanesoctocog alfa (BIVV001)

Intervention Type BIOLOGICAL

Pharmaceutical form: solution for injection Route of administration: IV injection

Arm B: On-Demand Then Prophylaxis

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.

Group Type EXPERIMENTAL

efanesoctocog alfa (BIVV001)

Intervention Type BIOLOGICAL

Pharmaceutical form: solution for injection Route of administration: IV injection

Interventions

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efanesoctocog alfa (BIVV001)

Pharmaceutical form: solution for injection Route of administration: IV injection

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* Participant, male or female, must be equal to or greater than 12 years of age inclusive, at the time of signing the informed consent.
* Severe hemophilia A, defined as less than (\<) 1 international units per deciliter (IU/dL) (\<1 percent \[%\]) endogenous FVIII activity as documented either by central laboratory testing at Screening or in historical medical records from a clinical laboratory demonstrating \<1% FVIII coagulant activity (FVIII:C) or a documented genotype known to produce severe hemophilia A.
* Previous treatment for hemophilia A (prophylaxis or on demand) with any recombinant and/or plasma-derived FVIII, or cryoprecipitate for at least 150 exposure days.
* Current regimen included one of the following:

* Prophylactic treatment regimen with a FVIII product or prophylactic emicizumab therapy for at least 6 months during the previous 12 months. Appropriate washout time needs to be taken into account.
* On-demand regimen with a FVIII product with a history of at least 12 bleeding episodes in the previous 12 months or at least 6 bleeding episodes in the previous 6 months prior to study enrollment.
* On-demand participant was accepted to move to a prophylaxis treatment regimen after 26-week on-demand period.
* Willingness and ability of the participant or surrogate (a caregiver or a family member greater than or equal to \[\>=\] 18 years of age) to complete training in the use of the study electronic Patient Diary (ePD) and to use the ePD throughout the study.
* Ability of the participant or his or her legally authorized representative (eg., parent or legal guardian) to understand the purpose and risks of the study, willing and able to comply with study requirements and provide signed and dated informed consent or assent (as applicable) and authorization to use protected health information in accordance with national and local participant privacy regulations.

Exclusion Criteria

* Clinically significant liver disease.
* Serious active bacterial or viral infection (other than chronic hepatitis or HIV) present within 30 days of screening.
* Other known coagulation disorder(s) in addition to hemophilia A.
* History of hypersensitivity or anaphylaxis associated with any FVIII product.
* Positive inhibitor results, defined as \>=0.6 Bethesda unit per milliliter (BU/mL) at screening. History of a positive inhibitor test defined as \>=0.6 BU/mL. Family history of inhibitors would not exclude the participant.
* Use of Emicizumab within the 20 weeks prior to screening.
* Major surgery within 8 weeks prior to screening.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bioverativ, a Sanofi company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

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Investigational Site Number 920

Los Angeles, California, United States

Site Status

Investigational Site Number 921

Los Angeles, California, United States

Site Status

Investigational Site Number 911

San Diego, California, United States

Site Status

Investigational Site Number 917

Gainesville, Florida, United States

Site Status

Investigational Site Number 919

Ann Arbor, Michigan, United States

Site Status

Investigational Site Number 908

Lansing, Michigan, United States

Site Status

Investigational Site Number 906

Las Vegas, Nevada, United States

Site Status

Investigational Site Number 902

Seattle, Washington, United States

Site Status

Investigational Site Number 136

Buenos Aires, , Argentina

Site Status

Investigational Site Number 137

Buenos Aires, , Argentina

Site Status

Investigational Site Number 139

Mendoza, , Argentina

Site Status

Investigational Site Number 121

Perth, , Australia

Site Status

Investigational Site Number 122

Sydney, , Australia

Site Status

Investigational Site Number 161

Brussels, , Belgium

Site Status

Investigational Site Number 181

Campinas, , Brazil

Site Status

Investigational Site Number 171

Plovdiv, , Bulgaria

Site Status

Investigational Site Number 172

Sofia, , Bulgaria

Site Status

Investigational Site Number 202

Hamilton, , Canada

Site Status

Investigational Site Number 205

Hamilton, , Canada

Site Status

Investigational Site Number 281

Brest, , France

Site Status

Investigational Site Number 283

Lille, , France

Site Status

Investigational Site Number 282

Lyon, , France

Site Status

Investigational Site Number 284

Marseille, , France

Site Status

Investigational Site Number 304

Berlin, , Germany

Site Status

Investigational Site Number 302

Bonn, , Germany

Site Status

Investigational Site Number 303

Frankfurt, , Germany

Site Status

Investigational Site Number 321

Athens, , Greece

Site Status

Investigational Site Number 312

Budapest, , Hungary

Site Status

Investigational Site Number 314

Debrecen, , Hungary

Site Status

Investigational Site Number 402

Milan, , Italy

Site Status

Investigational Site Number 401

Vicenza, , Italy

Site Status

Investigational Site Number 426

Kawasaki, , Japan

Site Status

Investigational Site Number 423

Kitakyushu, , Japan

Site Status

Investigational Site Number 425

Nagoya, , Japan

Site Status

Investigational Site Number 422

Nara, , Japan

Site Status

Investigational Site Number 421

Tokyo, , Japan

Site Status

Investigational Site Number 424

Tokyo, , Japan

Site Status

Investigational Site Number 435

Durango, , Mexico

Site Status

Investigational Site Number 641

Utrecht, , Netherlands

Site Status

Investigational Site Number 603

Daegu, , South Korea

Site Status

Investigational Site Number 600

Seoul, , South Korea

Site Status

Investigational Site Number 601

Seoul, , South Korea

Site Status

Investigational Site Number 521

Madrid, , Spain

Site Status

Investigational Site Number 531

Chang-hua, , Taiwan

Site Status

Investigational Site Number 532

Taipei, , Taiwan

Site Status

Investigational Site Number 581

Basingstoke, , United Kingdom

Site Status

Investigational Site Number 581

London, , United Kingdom

Site Status

Countries

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United States Argentina Australia Belgium Brazil Bulgaria Canada France Germany Greece Hungary Italy Japan Mexico Netherlands South Korea Spain Taiwan United Kingdom

References

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Klamroth R, von Drygalski A, Hermans C, Park YS, Chan AKC, Kupesiz A, Alvarez-Roman MT, Malec L, Santagostino E, Neill G, Bystricka L, Dumont J, Abad-Franch L, Fetita LS, Khoo L. Perioperative Management With Efanesoctocog Alfa in Patients With Haemophilia A in the Phase 3 XTEND-1 and XTEND-Kids Studies. Haemophilia. 2025 May;31(3):391-400. doi: 10.1111/hae.70017. Epub 2025 Mar 18.

Reference Type DERIVED
PMID: 40099428 (View on PubMed)

Weyand AC, Meunier S, Suzuki N, Bystricka L, Neill G, Abad-Franch L, Willemze A, Tosetto A. Treatment of Bleeding Episodes With Efanesoctocog Alfa in Previously Treated Patients With Severe Hemophilia A in the Phase 3 XTEND-1 Study. Am J Hematol. 2025 May;100(5):813-820. doi: 10.1002/ajh.27603. Epub 2025 Feb 10.

Reference Type DERIVED
PMID: 39927501 (View on PubMed)

DiBenedetti D, Neme D, Pan-Petesch B, Willemze A, Wynn T, Kragh N, Wilson A. Patient Experience With Efanesoctocog Alfa for Severe Hemophilia A: Results From the XTEND-1 Phase 3 Clinical Study Exit Interviews. Clin Ther. 2024 Dec;46(12):1016-1023. doi: 10.1016/j.clinthera.2024.09.010. Epub 2024 Oct 15.

Reference Type DERIVED
PMID: 39414418 (View on PubMed)

von Drygalski A, Chowdary P, Kulkarni R, Susen S, Konkle BA, Oldenburg J, Matino D, Klamroth R, Weyand AC, Jimenez-Yuste V, Nogami K, Poloskey S, Winding B, Willemze A, Knobe K; XTEND-1 Trial Group. Efanesoctocog Alfa Prophylaxis for Patients with Severe Hemophilia A. N Engl J Med. 2023 Jan 26;388(4):310-318. doi: 10.1056/NEJMoa2209226.

Reference Type DERIVED
PMID: 36720133 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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2019-002023-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1223-4867

Identifier Type: REGISTRY

Identifier Source: secondary_id

EFC16293

Identifier Type: -

Identifier Source: org_study_id

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