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

A Phase 3 Open-label, Multicenter Study of the Long-term Safety and Efficacy of Intravenous Recombinant Coagulation Factor VIII Fc-von Willebrand Factor-XTEN Fusion Protein (rFVIIIFc-VWF-XTEN; BIVV001) in Previously Treated Patients With Severe Hemophilia A

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

Participants will receive BIVV001 once weekly for a total of at least 100 exposure days to BIVV001 (including exposure during a BIVV001 parent study, if applicable). 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.

Inclusion criteria :

• 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.

Exclusion criteria:

• 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.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.