Clinical trial NCT04759131: Safety, Efficacy and PK of BIVV001 in Pediatric Patients With Hemophilia A
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hemophilia A
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2021-02-18
Enrollment: 74
Sex: MALE
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Objective:

- To evaluate the safety of BIVV001 in previously treated pediatric participants 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: Study duration per participants was approximately 60 weeks (maximum 8 weeks for screening and 52 weeks of treatment).

All participants completing or remaining at the end of study were offered participation in the planned extension trial.

Eligibility criteria: 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 international units per deciliter (IU/dL) (\<1 percent \[%\]) endogenous Factor VIII (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 exposure days (EDs) for participants aged 6 to \<12 years and above 50 EDs for participants 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 greater than or equal to (\>=) 0.6 Bethesda units (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 would not exclude the participant.
* Positive inhibitor test result, defined as \>=0.6 BU/mL at Screening.

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

Primary outcomes:
measure: Number of Participants With Neutralising Antibodies (Development of Inhibitors) Directed Against Factor VIII
timeFrame: Baseline up to Week 52
Secondary outcomes:
measure: Annualized Bleeding Rate (ABR): For Treated Bleeds
timeFrame: Baseline up to Week 52
measure: Sensitivity Analysis: Annualized Bleeding Rate: For Treated Bleeds
timeFrame: Baseline up to Week 52
measure: Annualized Bleeding Rate for All Bleeding Episodes
timeFrame: Baseline up to Week 52
measure: Sensitivity Analysis: Annualized Bleeding Rate for All Bleeding Episodes
timeFrame: Baseline up to Week 52
measure: Annualized Bleeding Rate by Type of Bleed (Spontaneous, Traumatic and Unknown Type)
timeFrame: Baseline up to Week 52
measure: Sensitivity Analysis: Annualized Bleeding Rate by Type of Bleed (Spontaneous, Traumatic and Unknown Type)
timeFrame: Baseline up to Week 52
measure: Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal and Skin/Mucosa)
timeFrame: Baseline up to Week 52
measure: Sensitivity Analysis: Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal and Skin/Mucosa)
timeFrame: Baseline up to Week 52
measure: Percentage of Participants Achieving FVIII Activity Levels Above 1%, 3%, 5%, 10%, 15%, and 20%
timeFrame: Baseline up to Week 52
measure: Number of Injections of BIVV001 Required to Treat a Bleeding Episode
timeFrame: Baseline up to Week 52
measure: Sensitivity Analysis: Number of Injections of BIVV001 Required to Treat a Bleeding Episode
timeFrame: Baseline up to Week 52
measure: Percentage of Bleeding Episodes Treated With a Single Injection of BIVV001
timeFrame: Baseline up to Week 52
measure: Sensitivity Analysis: Percentage of Bleeding Episodes Treated With a Single Injection of BIVV001
timeFrame: Baseline up to Week 52
measure: Total Dose of BIVV001 Required to Treat a Bleeding Episode
timeFrame: Baseline up to Week 52
measure: Sensitivity Analysis: Total Dose of BIVV001 Required to Treat a Bleeding Episode
timeFrame: Baseline up to Week 52
measure: Physicians' Global Assessment (PGA) of Participant's Response to BIVV001 Treatment Based on a 4-point Response Scale
timeFrame: Week 13 and Week 52/End of study (EOS)/Early termination (ET)
measure: Participant's Response to BIVV001 Treatment Based on the International Society on Thrombosis and Haemostasis (ISTH) 4-point Response Scale
timeFrame: Baseline up to Week 52
measure: Total Annualized BIVV001 Consumption Per Participant
timeFrame: Baseline up to Week 52
measure: Annualized Joint Bleeding Rate (AJBR)
timeFrame: Baseline up to Week 52
measure: Sensitivity Analysis: Annualized Joint Bleeding Rate (AJBR)
timeFrame: Baseline up to Week 52
measure: Change From Baseline in Hemophilia Joint Health Score Domain Score at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in Hemophilia Quality of Life Questionnaire (Haemo-QoL) Kids Short Version Total Score at Week 52 for Children Participants (Aged 4 to 7 and 8 to <12 Years)
timeFrame: Baseline, Week 52
measure: Change From Baseline in Hemophilia Quality of Life Questionnaire Parent Proxy Short Version Total Score at Week 52 for Children Participants (Aged 4 to 7 and 8 to <12 Years): Parent's Evaluation
timeFrame: Baseline, Week 52
measure: Change From Baseline in Hemophilia Quality of Life Questionnaire Kids Short Version Physical Health Domain Score at Week 52 for Children Participants (Aged 8 to <12 Years)
timeFrame: Baseline, Week 52
measure: Change From Baseline in Hemophilia Quality of Life Questionnaire Parent Proxy Short Version Physical Health Domain Score at Week 52 for Children Participants (Aged 8 to <12 Years): Parent's Evaluation
timeFrame: Baseline, Week 52
measure: Total Number of Target Joints Resolved in Participants at Week 52
timeFrame: Week 52
measure: Change From Baseline in Hemophilia Joint Health Score (HJHS) Total Score at Week 52
timeFrame: Baseline, Week 52
measure: Investigators' or Surgeons' Assessment of Participant's Hemostatic Response to BIVV001 Treatment
timeFrame: Baseline up to Week 52
measure: Number of Injections Per Surgery Required to Maintain Hemostasis During Perioperative Period for Major Surgery
timeFrame: During the perioperative period (any time during Baseline up to Week 52)
measure: Number of Blood Component Transfusions Used During Perioperative Period for Major Surgery
timeFrame: During the perioperative period (any time during Baseline up to Week 52)
measure: Total BIVV001 Consumption From Day -1 to 14 During Perioperative Period for Major Surgery
timeFrame: Day -1 to Day 14
measure: Type of Blood Component Transfusions Used During Perioperative Period for Major Surgery
timeFrame: During the perioperative period (any time during Baseline up to Week 52)
measure: Total Dose Required to Maintain Hemostasis From Day -1 to Day 0 During Perioperative Period for Major Surgery
timeFrame: Day -1 to Day 0 (day of surgery)
measure: Estimated Blood Loss During Major Surgery
timeFrame: Day 0 (i.e., day of surgery)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse (TESAEs)
timeFrame: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55)
measure: Number of Participants With Occurrence of Embolic and Thrombotic Events
timeFrame: Baseline up to Week 52
measure: Pharmacokinetics (PK): Maximum FVIII Activity (Cmax)
timeFrame: Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1
measure: Pharmacokinetics: Clearance (CL)
timeFrame: Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1
measure: Pharmacokinetics: Volume of Distribution at Steady State (Vss)
timeFrame: Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1
measure: Pharmacokinetics: Elimination Half-life (t1/2z)
timeFrame: Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1
measure: Pharmacokinetics: Area Under the Plasma FVIII Activity Versus Time Curve (AUC0-tau)
timeFrame: Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1
measure: Pharmacokinetics: Total Clearance at Steady State (CLss)
timeFrame: 0 hour - 168 hour at week 26, 39 or 52
measure: Pharmacokinetics: Incremental Recovery (IR)
timeFrame: Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1
measure: Pharmacokinetics: Trough Concentration for BIVV001 (Ctrough)
timeFrame: Pre-dose at Baseline (Day 1) and Week 52
measure: Pharmacokinetics: Mean Residence Time (MRT)
timeFrame: Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1
measure: Time Above Predefined (10% and 40%) FVIII Activity Levels
timeFrame: Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1
measure: Pharmacokinetics: Dose-normalized Area Under the Activity-time Curve (DNAUC0-tau)
timeFrame: Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles-Site Number:8400006
state: California
city: Gainesville
country: United States
facility: University of Florida-Site Number:8400009
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta-Site Number:8400019
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center-Site Number:8400001
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics-Site Number:8400002
state: Iowa
city: New York
country: United States
facility: NY Presbyterian - Weill Cornell Medical Center-Site Number:8400020
state: New York
city: Greenville
country: United States
facility: East Carolina University/Brody Medical Sciences Building-Site Number:8400015
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center-Site Number:8400008
state: Ohio
city: Columbus
country: United States
facility: Childrens Hospital Of Columbus-Site Number:8400012
state: Ohio
city: Milwaukee
country: United States
facility: Children's Hospital Of Wisconsin-Site Number:8400005
state: Wisconsin
city: Westmead
country: Australia
facility: Investigational Site Number :0360001
state: New South Wales
city: South Brisbane
country: Australia
facility: Investigational Site Number :0360002
state: Queensland
city: Hamilton
country: Canada
facility: Investigational Site Number :1240004
state: Ontario
city: London
country: Canada
facility: Investigational Site Number :1240003
state: Ontario
city: Ottawa
country: Canada
facility: Investigational Site Number :1240002
state: Ontario
city: Toronto
country: Canada
facility: Investigational Site Number :1240001
state: Ontario
city: Bron
country: France
facility: Investigational Site Number :2500004
city: Kremlin Bicetre
country: France
facility: Investigational Site Number :2500001
city: Lille
country: France
facility: Investigational Site Number :2500003
city: Frankfurt am Main
country: Germany
facility: Investigational Site Number :2760001
city: München
country: Germany
facility: Investigational Site Number :2760002
city: Pécs
country: Hungary
facility: Investigational Site Number :3480005
city: Dublin
country: Ireland
facility: Investigational Site Number :3720001
city: Milano
country: Italy
facility: Investigational Site Number :3800001
city: Napoli
country: Italy
facility: Investigational Site Number :3800002
city: Amsterdam
country: Netherlands
facility: Investigational Site Number :5280002
city: Utrecht
country: Netherlands
facility: Investigational Site Number :5280001
city: Esplugues de Llobregat
country: Spain
facility: Investigational Site Number :7240002
state: Catalunya [Cataluña]
city: Madrid
country: Spain
facility: Investigational Site Number :7240001
state: Madrid, Comunidad De
city: Malmö
country: Sweden
facility: Investigational Site Number :7520001
city: Zürich
country: Switzerland
facility: Investigational Site Number :7560001
city: Taichung
country: Taiwan
facility: Investigational Site Number :1580001
city: Taichung
country: Taiwan
facility: Investigational Site Number :1580003
city: Taipei
country: Taiwan
facility: Investigational Site Number :1580002
city: Taipei
country: Taiwan
facility: Investigational Site Number :1580004
city: Antalya
country: Turkey
facility: Investigational Site Number :7920004
city: Istanbul
country: Turkey
facility: Investigational Site Number :7920001
city: Izmir
country: Turkey
facility: Investigational Site Number :7920003
city: Birmingham
country: United Kingdom
facility: Investigational Site Number :8260003
city: London
country: United Kingdom
facility: Investigational Site Number :8260001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: