Safety, Efficacy and PK of BIVV001 in Pediatric Patients With Hemophilia A

Study Overview
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Brief Summary
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Primary Objective: - To evaluate the safety of BIVV001 in previously treated pediatric 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 efficacy of BIVV001 for perioperative management To evaluate the safety and tolerability of BIVV001 treatment To assess the pharmacokinetics (PK) of BIVV001

Detailed Description
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Study duration per participants will be approximately 60 weeks (maximum 8 weeks for screening and 52 weeks of treatment) All participants completing or remaining at the end of study will be offered participation in the planned extension trial.

Official Title
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A Phase 3 Open-label, Multicenter Study of the Safety, Efficacy, and Pharmacokinetics of Intravenous Recombinant Coagulation Factor VIII Fc-von Willebrand Factor-XTEN Fusion Protein (rFVIIIFc-VWF-XTEN; BIVV001) in Previously Treated Pediatric Patients <12 Years of Age With Severe Hemophilia A

Conditions
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Hemophilia A

Intervention / Treatment
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* Drug: efanesoctocog alfa (BIVV001)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Participant must be younger than 12 years of age, at the time of signing the informed consent Severe hemophilia A defined as <1 IU/dL (<1%) endogenous FVIII 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 for patients aged 6-11 years and above 50 EDs for patients aged <6 years Weight above or equal to 10 kg. Exclusion criteria: 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 result, defined as ≥0.6 BU/mL at Screening. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Maximum Age: 12 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prophylaxis<br>Participants will receive weekly dose of BIVV001 for 52 weeks. | Drug: efanesoctocog alfa (BIVV001)<br>* Pharmaceutical form:solution for injection Route of administration: Intravenous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of inhibitor development | The occurrence of inhibitor development (neutralizing antibodies directed against factor VIII [FVIII]) as determined via the Nijmegen modified Bethesda assay | baseline to 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized bleeding rate (ABR) levels | Annualized bleeding rate (ABR) for treated, for untreated, for all bleeding episodes. | baseline to week 52 | 
| Annualized bleeding rate (ABR) by type of bleed | ABR by type of bleed such as spontaneous or traumatic | baseline to week 52 | 
| Annualized bleeding rate (ABR) by location of bleed | ABR by location of bleed such as joint, muscle, internal, or skin/mucosa | baseline to week 52 | 
| Percentage of participants who maintain FVIII activity above prespecified levels |  | baseline to week 52 | 
| Number of injection and dose of BIVV001 to treat a bleeding episode |  | baseline to week 52 | 
| Percentage of bleeding episodes treated with a single injection of BIVV001 |  | baseline to week 52 | 
| 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. | 52 weeks | 
| Physician's global assessment of the participant's response based on BIVV001 treatment | Physician's global assessment (PGA) of participant's response to BIVV001 treatment based on a 4-point response scale | baseline to week 52 | 
| Total annualized BIVV001 consumption |  | baseline to week 52 | 
| Annualized Joint Bleeding Rate (AJBR) |  | baseline to week 52 | 
| Target joint resolution | Target joint resolution at week 52, based on ISTH criteria. | At week 52 | 
| Change in Hemophilia Joint Health Score (HJHS) total score and domain scores | Change from baseline to week 52 in total score and domain scores (eg, swelling and strength) assessed by the HJHS. | baseline to week 52 | 
| Changes in Haemophilia Quality of Life Questionnaire for Children (Haemo-QoL) total score | Changes in Haemophilia Quality of Life Questionnaire for Children (Haemo-QoL) total score from baseline to Week 52 (≥ 4 years old and parent proxy for all ages) | baseline to week 52 | 
| Changes in Haemophilia Quality of Life Questionnaire for Children (Haemo-QoL) physical health domain scores from | Changes in Haemophilia Quality of Life Questionnaire for Children (Haemo-QoL) physical health domain scores from baseline to Week 52 (≥ 4 years old and parent proxy for all ages) | baseline to week 52 | 
| 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 | baseline to week 52 | 
| Number of injections and dose to maintain hemostasis during perioperative period for major surgery |  | baseline to week 52 | 
| Total BIVV001 consumption during perioperative period for major surgery |  | baseline to week 52 | 
| Number of blood component transfusions used during perioperative period for major surgery |  | baseline to week 52 | 
| Type of blood component transfusions used during perioperative period for major surgery |  | baseline to week 52 | 
| Estimated blood loss during perioperative period for major surgery |  | baseline to week 52 | 
| Number of participants with occurence of adverse events (AEs) and serious adverse events (SAEs) | Participants with ocurrence of adverse events (AEs) and serious adverse events (SAEs) | baseline to week 52 | 
| Number of participants with occurrence of embolic and thrombotic events |  | baseline to week 52 | 
| PK parameter: Maximum activity (Cmax) |  | baseline to week 52 | 
| PK parameter: Elimination half-life (t1/2) |  | baseline (day 1) | 
| PK parameter: Total clearance (CL) |  | baseline (day 1) | 
| PK parameter: Total clearance at steady state (CLss) |  | baseline (day 1) | 
| PK parameter:dose-normalized area under the activity-time curve (DNAUC) |  | baseline (day 1) | 
| PK parameter: Area under the activity time curve (AUC) |  | baseline (day 1) | 
| PK parameter: Volume of distribution at steady state (Vss) |  | baseline (day 1) | 
| PK parameter: Mean residence time (MRT) |  | baseline (day 1) | 
| PK parameter: Incremental recovery (IR) |  | baseline to week 52 | 
| PK parameter: Trough activity (Ctrough) |  | baseline to week 52 | 
| PK parameter: Time above predefined FVIII activity levels |  | baseline (day 1) |