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 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: EFC162932019-002023-15U1111-1223-4867
• Study Type: interventional
• Target: 159
• Locations: 19 countries
• Sites: 47

Brief Summary

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.

Conditions

Factor VIII Deficiency

Outcome Measures

Primary Outcomes (2)

• 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).

  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).

  Baseline to Week 52

Secondary Outcomes (45)

• 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

• 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

• 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

• 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

• 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

Study Arms (2)

Arm A: Prophylaxis

EXPERIMENTAL

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)

Arm B: On-Demand Then Prophylaxis

EXPERIMENTAL

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)

Interventions

efanesoctocog alfa (BIVV001) BIOLOGICAL

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

Arm A: Prophylaxis; Arm B: On-Demand Then Prophylaxis

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bioverativ, a Sanofi company: lead

Study Sites (47)

Investigational Site Number 920

Los Angeles, California, 90007-2664, United States

Location

Investigational Site Number 921

Los Angeles, California, 90027, United States

Location

Investigational Site Number 911

San Diego, California, 92121, United States

Location

Investigational Site Number 917

Gainesville, Florida, 32610, United States

Location

Investigational Site Number 919

Ann Arbor, Michigan, 48109, United States

Location

Investigational Site Number 908

Lansing, Michigan, 48824, United States

Location

Investigational Site Number 906

Las Vegas, Nevada, 89113, United States

Location

Investigational Site Number 902

Seattle, Washington, 98101-3932, United States

Location

Investigational Site Number 136

Buenos Aires, Argentina

Location

Investigational Site Number 137

Buenos Aires, Argentina

Location

Investigational Site Number 139

Mendoza, Argentina

Location

Investigational Site Number 121

Perth, Australia

Location

Investigational Site Number 122

Sydney, Australia

Location

Investigational Site Number 161

Brussels, Belgium

Location

Investigational Site Number 181

Campinas, Brazil

Location

Investigational Site Number 171

Plovdiv, Bulgaria

Location

Investigational Site Number 172

Sofia, Bulgaria

Location

Investigational Site Number 202

Hamilton, Canada

Location

Investigational Site Number 205

Hamilton, Canada

Location

Investigational Site Number 281

Brest, France

Location

Investigational Site Number 283

Lille, France

Location

Investigational Site Number 282

Lyon, France

Location

Investigational Site Number 284

Marseille, France

Location

Investigational Site Number 304

Berlin, Germany

Location

Investigational Site Number 302

Bonn, Germany

Location

Investigational Site Number 303

Frankfurt, Germany

Location

Investigational Site Number 321

Athens, Greece

Location

Investigational Site Number 312

Budapest, Hungary

Location

Investigational Site Number 314

Debrecen, Hungary

Location

Investigational Site Number 402

Milan, Italy

Location

Investigational Site Number 401

Vicenza, Italy

Location

Investigational Site Number 426

Kawasaki, Japan

Location

Investigational Site Number 423

Kitakyushu, Japan

Location

Investigational Site Number 425

Nagoya, Japan

Location

Investigational Site Number 422

Nara, Japan

Location

Investigational Site Number 421

Tokyo, Japan

Location

Investigational Site Number 424

Tokyo, Japan

Location

Investigational Site Number 435

Durango, Mexico

Location

Investigational Site Number 641

Utrecht, Netherlands

Location

Investigational Site Number 603

Daegu, South Korea

Location

Investigational Site Number 600

Seoul, South Korea

Location

Investigational Site Number 601

Seoul, South Korea

Location

Investigational Site Number 521

Madrid, Spain

Location

Investigational Site Number 531

Chang-hua, Taiwan

Location

Investigational Site Number 532

Taipei, Taiwan

Location

Investigational Site Number 581

Basingstoke, United Kingdom

Location

Investigational Site Number 581

London, United Kingdom

Location

Related Publications (5)

• Susen S, Kulkarni R, Nogami K, Peyvandi F, Konkle B, Santagostino E, Khan U, Willemze A, Bystricka L, Dumont J, Chowdary P. Outcomes in participants switching from FVIII replacement therapy to efanesoctocog alfa prophylaxis in XTEND-1: a post hoc analysis. Ther Adv Hematol. 2026 Jan 20;17:20406207251398986. doi: 10.1177/20406207251398986. eCollection 2026.

  PMID: 41583536 DERIVED

• 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.

  PMID: 40099428 DERIVED

• 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.

  PMID: 39927501 DERIVED

• 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.

  PMID: 39414418 DERIVED

• 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.

  PMID: 36720133 DERIVED

Related Links

• EFC16293 Plain Language Results Summary

MeSH Terms

Conditions

Hemophilia A

Interventions

BIVV001

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@Sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2019
• First Posted: November 13, 2019
• Study Start: November 19, 2019
• Primary Completion: February 3, 2022
• Study Completion: February 3, 2022
• Last Updated: September 17, 2025
• Results First Posted: May 24, 2023

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

JP (6); CA (2); FR (4); ME (1); AR (3); BR (1); HU (2); NL (1); DE (3); US (8); BU (2); GR (1); BE (1); KR (3); IT (2); ES (1); TW (2); AU (2); GB (2)