Long-term Safety and Efficacy of Efanesoctocog Alfa (BIVV001) in Previously Treated Patients With Hemophilia A

NCT04644575 | Active Not Recruiting Phase 3 FDA Drug

• 4 other identifiers: LTS16294U1111-1244-05172023-508929-27-002020-002215-22
• Study Type: interventional
• Target: 261
• Locations: 23 countries
• Sites: 85

Brief Summary

Primary Objective: \- To evaluate the long-term safety of BIVV001 in previously treated subjects with hemophilia A 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 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 (QoL) outcomes.
• To evaluate the safety and tolerability of BIVV001 treatment.
• To assess the PK of BIVV001 based on the one stage activated partial thromboplastin time (aPTT) and two-stage chromogenic FVIII activity assays (only applicable to Arm B).
• To evaluate the efficacy of BIVV001 for perioperative management

Conditions

Hemophilia A

Outcome Measures

Primary Outcomes (1)

• Number of participants with the occurrence of inhibitor development (neutralizing antibodies detected against factor VIII [FVIII])

  The number of participants with the occurrence of inhibitor development (neuatralizing antibodies detected against factor VIII \[FVIII\]) as determined via the Nijmegen modified Bethesda assay.

  Baseline to month 48

Secondary Outcomes (33)

• Annual bleeding rate (ABR)

  Baseline to month 48

• Annualized bleeding rate (ABR) by type of bleed

  Baseline to month 48

• Annualized bleeding rate (ABR) by location

  Baseline to month 48

• Percentage of patients who maintain factor VIII (FVIII) above prespecified activity levels

  Baseline to month 48

• Number of injections and dose of BIVV0001 to treat a bleeding episode

  Month 48

Study Arms (3)

Arm A: Previously treated in BIVV001 study

EXPERIMENTAL

This arm includes participants who have completed study EFC16293 or study EFC16295, participants who have completed Arm B or Arm C of this study (LTS16294) and roll over into Arm A, and participants who have completed any other potential BIVV001 study. Participants in this arm will continue receiving BIVV001 prophylaxis treatment once weekly (QW) for a total of 100 exposure days (EDs) cumulative from the parent study and this study. Participants will have the opportunity to continue in this study for up to 4 years, unless BIVV001 is commercially available in their applicable participating country.

Drug: efanesoctocog alfa (BIVV001)

Arm B: Newly initiated (China Only) in BIVV001

EXPERIMENTAL

This arm includes Chinese participants of any age who will be newly initiated on BIVV001 prophylaxis treatment once-weekly (QW) for 52 weeks. After 52 weeks of treatment in this arm B, participants will be able to roll over into arm A.

Drug: efanesoctocog alfa (BIVV001)

Arm C: Newly initiated in BIVV001 with planned major surgery

EXPERIMENTAL

This arm includes participants of any age who will be newly initiated on BIVV001 prophylaxis treatment once-weekly (QW) and will undergo planned major surgery after at least 6 initial EDs with BIVV001, and within 26 weeks from Day 1. After 52 weeks of treatment in arm C, participants will be able to roll into arm A.

Drug: efanesoctocog alfa (BIVV001)

Interventions

efanesoctocog alfa (BIVV001) DRUG

Pharmaceutical form:Solution for Injection Route of administration: Intravenous

Arm A: Previously treated in BIVV001 study; Arm B: Newly initiated (China Only) in BIVV001; Arm C: Newly initiated in BIVV001 with planned major surgery

Eligibility Criteria

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

You may qualify if:

• For participants rolling over into Arm A
• Participants who have completed the studies EFC16923, EFC16925, Arm B or Arm C of the current study, or any other potential BIVV001 study.
• Male or Female
• For participants new to BIVV001 (Arm B and C)
• Participants who have severe hemophilia A, defined as \<1 IU/dL (\<1%) 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 EDs or 50 EDs for participants aged \<6 years.
• Platelet count ≥100 000 cells/μL at screening.
• A participant known to be human immunodeficiency virus (HIV) antibody positive, either previously documented or identified from screening assessments, must have the following results prior to enrollment: CD4 lymphocyte count \>200 cells/mm³ and viral load of \<400 000 copies/mL
• Male
• Only for Arm B: Chinese participants
• Only for Arm C: planned major surgery within 6 months after Day 1.

You may not qualify if:

• For participants rolling over into Arm A
• Positive inhibitor result, defined as ≥0.6 Bethesda units (BU)/mL.
• Participation in another study.
• For participants new to BIVV001 (Arm B and Arm C)
• Any concurrent clinically significant liver disease that, in the opinion of the Investigator, would make the participant unsuitable for enrollment. This may include, but is not limited to cirrhosis, portal hypertension, and acute hepatitis.
• Serious active bacterial, fungal, 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.
• History of a positive inhibitor (to FVIII) test defined as ≥0.6 BU/mL, or any value greater than or equal to the lower sensitivity cut-off for laboratories with cut-offs for inhibitor detection between 0.7 and 1.0 BU/mL, or clinical signs or symptoms of decreased response to FVIII administrations. Family history of inhibitors will not exclude the participant.
• Positive inhibitor test (FVIII) result, defined as ≥0.6 BU/mL at screening.
• Treatment with acetylsalicylic acid (ASA) or antiplatelet agents that are not nonsteroidal anti-inflammatory drugs (NSAIDs) within 2 weeks prior to screening.
• Treatment with NSAIDs greater than the maximum dose specified in the regional prescribing information within 2 weeks prior to screening.
• Systemic treatment within 12 weeks prior to Screening with chemotherapy and/or other immunosuppressive drugs (except for the treatment of hepatitis C virus \[HCV\] or HIV).
• Emicizumab use within the 20 weeks prior to screening.
• Major surgery within 8 weeks prior to screening.

Sponsors & Collaborators

• Bioverativ, a Sanofi company: lead

Study Sites (85)

Orthopaedic Institute for Children Site Number : 8400003

Los Angeles, California, 90007, United States

Location

Children's Hospital Los Angeles Site Number : 8400009

Los Angeles, California, 90027, United States

Location

University of California San Diego Site Number : 8400007

San Diego, California, 92121, United States

Location

University of Florida Health Site Number : 8400008

Gainesville, Florida, 32608, United States

Location

Children's Healthcare of Atlanta Site Number : 8400016

Atlanta, Georgia, 30322, United States

Location

Rush University Medical Center Site Number : 8400010

Chicago, Illinois, 60612-3833, United States

Location

Children's Hospital Of Iowa Site Number : 8400011

Iowa City, Iowa, 52242, United States

Location

University of Michigan Medical Center Site Number : 8400006

Ann Arbor, Michigan, 48109, United States

Location

Michigan State University School Of Med Site Number : 8400002

East Lansing, Michigan, 48824, United States

Location

Hemostasis and Thrombosis Center of Nevada Site Number : 8400001

Las Vegas, Nevada, 89113, United States

Location

New York Presbyterian Hospital/Weill Cornell Medical Center Site Number : 8400017

New York, New York, 10021, United States

Location

East Carolina University -2390 Hemby Ln Site Number : 8400015

Greenville, North Carolina, 27834, United States

Location

Cincinnati Children's Hospital Medical Center Site Number : 8400012

Cincinnati, Ohio, 45229, United States

Location

Children's Research Institute Site Number : 8400013

Columbus, Ohio, 43205-2696, United States

Location

Bloodworks Northwest Site Number : 8400005

Seattle, Washington, 98104, United States

Location

Children's Hospital of Wisconsin Site Number : 8400014

Milwaukee, Wisconsin, 53226-0509, United States

Location

Investigational Site Number : 0320001

CABA, Buenos Aires F.D., C1425BWE, Argentina

Location

Investigational Site Number : 0320002

Godoy Cruz, Mendoza Province, M5504FKD, Argentina

Location

Investigational Site Number : 0320003

Buenos Aires, C1015ABO, Argentina

Location

Investigational Site Number : 0360004

Camperdown, New South Wales, 2050, Australia

Location

Investigational Site Number : 0360001

Westmead, New South Wales, 2145, Australia

Location

Investigational Site Number : 0360002

South Brisbane, Queensland, 4101, Australia

Location

Investigational Site Number : 0360003

Murdoch, Western Australia, 6961, Australia

Location

Investigational Site Number : 0560003

Woluwe-Saint-Lambert, 1200, Belgium

Location

Hemocentro Campinas - UNICAMP Site Number : 0760001

Campinas, São Paulo, 13083-970, Brazil

Location

Investigational Site Number : 1000171

Plovdiv, 4002, Bulgaria

Location

Investigational Site Number : 1000172

Sofia, 1756, Bulgaria

Location

Investigational Site Number : 1240005

Hamilton, Ontario, L8L 8E7, Canada

Location

Investigational Site Number : 1240004

Hamilton, Ontario, L8N 3Z5, Canada

Location

Investigational Site Number : 1240002

Ottawa, Ontario, K1H 8L1, Canada

Location

Investigational Site Number : 1240001

Toronto, Ontario, M5G 1X8, Canada

Location

Investigational Site Number : 1560002

Beijing, 100045, China

Location

Investigational Site Number : 1560006

Beijing, 100730, China

Location

Investigational Site Number : 1560001

Guangzhou, 510515, China

Location

Investigational Site Number : 1560003

Hangzhou, 310003, China

Location

Investigational Site Number : 1560004

Hangzhou, 310003, China

Location

Investigational Site Number : 1560005

Jinan, 250013, China

Location

Investigational Site Number : 1560009

Kunming, 650032, China

Location

Investigational Site Number : 1560010

Kunming, 650101, China

Location

Investigational Site Number : 1560013

Lanzhou, 730000, China

Location

Investigational Site Number : 1560007

Suzhou, 215006, China

Location

Investigational Site Number : 2500005

Brest, 29200, France

Location

Investigational Site Number : 2500004

Bron, 69500, France

Location

Investigational Site Number : 2500001

Le Kremlin-Bicêtre, 94275, France

Location

Investigational Site Number : 2500003

Lille, 59037, France

Location

Investigational Site Number : 2500006

Marseille, 13385, France

Location

Investigational Site Number : 2760304

Berlin, 10249, Germany

Location

Investigational Site Number : 2760302

Bonn, 53127, Germany

Location

Investigational Site Number : 2760001

Frankfurt am Main, 60590, Germany

Location

Investigational Site Number : 2760002

München, 80337, Germany

Location

Investigational Site Number : 3000001

Athens, 11527, Greece

Location

Investigational Site Number : 3480002

Budapest, 1134, Hungary

Location

Investigational Site Number : 3480004

Debrecen, 4093, Hungary

Location

Investigational Site Number : 3480005

Pécs, 7623, Hungary

Location

Investigational Site Number : 3720001

Dublin, D12 N512, Ireland

Location

Investigational Site Number : 3800002

Napoli, Campania, 80123, Italy

Location

Investigational Site Number : 3800001

Milan, 20121, Italy

Location

Investigational Site Number : 3800003

Vicenza, 36100, Italy

Location

Investigational Site Number : 3920425

Nagoya, Aichi-ken, 466-0065, Japan

Location

Investigational Site Number : 3920423

Kitakyushu-shi, Fukuoka, 807-8556, Japan

Location

Investigational Site Number : 3920426

Kawasaki-shi, Kanagawa, 216-8511, Japan

Location

Investigational Site Number : 3920422

Kashihara-Shi, Niigata, 634-8521, Japan

Location

Investigational Site Number : 3920421

Shinjuku-ku, Tokyo, 160-0023, Japan

Location

Investigational Site Number : 3920424

Suginami-ku, Tokyo, 167-0035, Japan

Location

Investigational Site Number : 5280002

Amsterdam, 1105 AZ, Netherlands

Location

Investigational Site Number : 5280001

Utrecht, 3584 CX, Netherlands

Location

Investigational Site Number : 4100603

Daegu, Daegu, 41404, South Korea

Location

Investigational Site Number : 4100601

Seoul, Seoul-teukbyeolsi, 03722, South Korea

Location

Investigational Site Number : 4100600

Seoul, Seoul-teukbyeolsi, 05278, South Korea

Location

Investigational Site Number : 7240002

Esplugues de Llobregat, Catalunya [Cataluña], 08950, Spain

Location

Investigational Site Number : 7240001

Madrid, Madrid, Comunidad de, 28046, Spain

Location

Investigational Site Number : 7520001

Malmo, 20502, Sweden

Location

Investigational Site Number : 7560001

Zurich, 8032, Switzerland

Location

Investigational Site Number : 1580005

Changhua County, 500, Taiwan

Location

Investigational Site Number : 1580001

Taichung, 40201, Taiwan

Location

Investigational Site Number : 1580003

Taichung, 407, Taiwan

Location

Investigational Site Number : 1580002

Taipei, 10002, Taiwan

Location

Investigational Site Number : 1580004

Taipei, 11031, Taiwan

Location

Investigational Site Number : 7920004

Antalya, 07059, Turkey (Türkiye)

Location

Investigational Site Number : 7920001

Istanbul, 34390, Turkey (Türkiye)

Location

Investigational Site Number : 7920003

Izmir, TR-35100, Turkey (Türkiye)

Location

Investigational Site Number : 8260005

London, London, City of, NW3 2QG, United Kingdom

Location

Investigational Site Number : 8260001

London, London, City of, WC1N 3JH, United Kingdom

Location

Investigational Site Number : 8260003

Birmingham, B4 6NH, United Kingdom

Location

Investigational Site Number : 8260004

Hampshire, RG24 9NA, United Kingdom

Location

Related Publications (1)

• Quintilla JM, de la Gala C, Berrueco R, Claverol J, Figueres B, Bergos A, Rodriguez L, Mora A, DiBiaso V, Llanos C, Nafria B. High-Fidelity Clinical Simulation to Improve a Pediatric Clinical Trial Design: Lessons Learned and Conceptualization of the Return on Investment (ROI) and Return on Engagement (ROE) Analysis. Paediatr Drugs. 2025 Jan;27(1):73-84. doi: 10.1007/s40272-024-00660-8. Epub 2024 Nov 25.

  PMID: 39585605 DERIVED

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

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

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

Model Details: It is a 3-arm study with single intervention

Study Record Dates

• First Submitted: November 23, 2020
• First Posted: November 25, 2020
• Study Start: February 23, 2021
• Primary Completion (Estimated): January 15, 2027
• Study Completion (Estimated): January 15, 2027
• Last Updated: August 1, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

AU (4); JP (6); TW (5); TU (3); ES (2); SE (1); GB (4); BU (2); FR (5); DE (4); NL (2); US (16); GR (1); KR (3); CH (1); IT (3); BR (1); CA (4); AR (3); CN (10); IE (1); BE (1); HU (3)