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 (XTEND-1)

Bioverativ

Status and phase: Completed; Phase 3

Conditions: Factor VIII Deficiency

Treatments: Biological: efanesoctocog alfa (BIVV001)

Study type: Interventional

Funder types: Industry

Identifiers

NCT04161495

EFC16293

2019-002023-15 (EudraCT Number)

U1111-1223-4867 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 159 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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159 participants in 2 patient groups

Arm A: Prophylaxis

Experimental group

Description:

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.

Treatment:

Biological: efanesoctocog alfa (BIVV001)

Arm B: On-Demand Then Prophylaxis

Experimental group

Description:

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.

Treatment:

Biological: efanesoctocog alfa (BIVV001)