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

Phase 3Active Not RecruitingNCT04644575

Bioverativ, a Sanofi company261 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

261

Conditions

Hemophilia A

Interventions

Eligibility

Sex: ALL

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

Time frame: Baseline to month 48

Secondary Outcomes

Annual bleeding rate (ABR)

Annualized bleeding rate (ABR) for treated bleeding episodes and all bleeding episodes (including untreated bleeds).

Time frame: Baseline to month 48

Annualized bleeding rate (ABR) by type of bleed

Annualized bleeding rate (ABR) by type during prophylaxis treatment per study arm and parent study.

Time frame: Baseline to month 48

Annualized bleeding rate (ABR) by location

Annualized bleeding rate (ABR) by location during prophylaxis treatment per study arm and parent study.

Time frame: Baseline to month 48

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

Percentage of participants who maintain factor VIII (FVIII) activity levels over 7 days post dose during prophylaxis treatment per study arm and per parent study or arm.

Time frame: Baseline to month 48

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

Time frame: Month 48

Percentage of bleeding episode treated with a single injection of BIVV001

Time frame: Month 48

Assessment of response to BIVV001 treatment of individual bleeding episodes

Assessment of response to BIVV001 treatment of individual bleeding episodes based on the International Society on Thrombosis and Haemostasis (ISTH) 4-point response scale

Time frame: Baseline to month 48

Physician's global assessment (PGA) of participants response to BIVV001

Physician's global assessment (PGA) of participant's response to BIVV001 treatment based on a 4-point response scale .

Time frame: Baseline to month 48

Total annualized BIVV001 consumption

Total annualized BIVV001 consumption per participant during prophylaxis treatment

Time frame: Baseline to month 48

Annualized joint bleeding rate (AJBR)

Time frame: Baseline to month 48

Target joint resolution

Target joint development, resolution and maintenance of target joint resolution based on ISTH criteria.

Time frame: Month 48

Change from baseline in Hemophilia Joint Health Score (HJHS)

Change from Baseline to the end of study visit in total score and domain scores (eg, swelling and strength) assessed by the Hemophilia Joint Health Score (HJHS)

Time frame: Baseline to month 48

Change from baseline in PROMIS-SF Physical Function

Change in Quality of Life (QoL) measures from baseline to end of study visit per study arm and per parent study arm: PROMIS-SF Physical Function (participants aged ≥18 years old).)

Time frame: Baseline to month 48

Change from baseline in Haem-A-QoL total score and physical health score

Change from baseline in Haemophilia QoL Questionnaire for Adults (Haem-A-QoL) total and physical health domain score on participants aged ≥17 years old.

Time frame: Baseline to month 48

Change from baselin in Haemo-QoL total score and physical health score

Change from baseline in Haemophilia QoL Questionnaire for Children (Haemo-QoL) total and physical health domain score on participants aged ≥4 to 16 years old and parent proxy for participants aged ≥4 to to \<12 years old.

Time frame: Baseline to month 48

Number of participants with adverse events (AEs) and serious adverse events (SAEs)

Participants with occurrences of treatment emergent adverse events (AEs) and serious adverse events (SAEs).

Time frame: Baseline to month 48

Number of participants with the occurrence of embolic and thrombotic events

Participants with the occurrence of embolic and thrombotic events.

Time frame: Baseline to month 48

PK parameter: Maximum activity (Cmax)

Time frame: Baseline to week 52

PK parameter: Elimination half-life (t1/2)

Time frame: Baseline to week 26

PK parameter: Total clearance (CL)

Time frame: Baseline to week 26

PK parameter: Total clearance at steady state (CLss)

Time frame: Baseline to week 26

PK parameter: Accumulation index (AI)

Time frame: Baseline to week 26

PK parameter: Area under the activity time curve (AUC)

Time frame: Baseline to week 26

PK parameter: Volume of distribution at steady state (Vss)

Time frame: Baseline to week 26

PK parameter: Mean residence time (MRT)

Time frame: Baseline to week 26

PK parameter: Incremental recovery (IR)

Time frame: Baseline to week 52

PK parameter: Trough activity (Ctrough)

Time frame: Baseline to week 52

PK parameter: Time above FVIII activity levels

Time frame: Baseline to week 26

Investigators' or Surgeons' assessment of participant's hemostatic response to BIVV001 treatment

Investigators' or Surgeons' assessment of participant's hemostatic response to BIVV001 treatment on the ISTH 4 point response for surgical procedures scale.

Time frame: Baseline to month 48

Number of injections and dose to maintain hemostasis during perioperative period for major surgery

Time frame: Baseline to month 48

Total BIVV001 consumption during perioperative period for major surgery

Time frame: Baseline to month 48

Number and type of blood component transfusions used during perioperative period for major surgery

Time frame: Baseline to month 48

Estimated blood loss during perioperative period for major surgery

Time frame: Baseline to month 48

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

Overview

Conditions

Interventions

Eligibility

Locations (85)

Outcomes

Primary Outcomes

Secondary Outcomes