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Safety, Efficacy and PK of BIVV001 in Pediatric Patients With Hemophilia A (XTEND-Kids)

Primary Purpose

Hemophilia A

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
efanesoctocog alfa (BIVV001)
Sponsored by
Bioverativ, a Sanofi company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hemophilia A

Eligibility Criteria

undefined - 12 Years (Child)MaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Children's Hospital Los Angeles-Site Number:8400006
  • University of Florida-Site Number:8400009
  • Children's Healthcare of Atlanta-Site Number:8400019
  • Rush University Medical Center-Site Number:8400001
  • University of Iowa Hospitals and Clinics-Site Number:8400002
  • NY Presbyterian - Weill Cornell Medical Center-Site Number:8400020
  • East Carolina University/Brody Medical Sciences Building-Site Number:8400015
  • Cincinnati Children's Hospital Medical Center-Site Number:8400008
  • Childrens Hospital Of Columbus-Site Number:8400012
  • Children's Hospital Of Wisconsin-Site Number:8400005
  • Investigational Site Number :0360001
  • Investigational Site Number :0360002
  • Investigational Site Number :1240004
  • Investigational Site Number :1240003
  • Investigational Site Number :1240002
  • Investigational Site Number :1240001
  • Investigational Site Number :2500004
  • Investigational Site Number :2500001
  • Investigational Site Number :2500003
  • Investigational Site Number :2760001
  • Investigational Site Number :2760002
  • Investigational Site Number :3480005
  • Investigational Site Number :3720001
  • Investigational Site Number :3800001
  • Investigational Site Number :3800002
  • Investigational Site Number :5280002
  • Investigational Site Number :5280001
  • Investigational Site Number :7240002
  • Investigational Site Number :7240001
  • Investigational Site Number :7520001
  • Investigational Site Number :7560001
  • Investigational Site Number :1580001
  • Investigational Site Number :1580003
  • Investigational Site Number :1580002
  • Investigational Site Number :1580004
  • Investigational Site Number :7920004
  • Investigational Site Number :7920001
  • Investigational Site Number :7920003
  • Investigational Site Number :8260003
  • Investigational Site Number :8260001

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Prophylaxis

Arm Description

Participants will receive weekly dose of BIVV001 for 52 weeks.

Outcomes

Primary Outcome Measures

Occurrence of inhibitor development
The occurrence of inhibitor development (neutralizing antibodies directed against factor VIII [FVIII]) as determined via the Nijmegen modified Bethesda assay

Secondary Outcome Measures

Annualized bleeding rate (ABR) levels
Annualized bleeding rate (ABR) for treated, for untreated, for all bleeding episodes.
Annualized bleeding rate (ABR) by type of bleed
ABR by type of bleed such as spontaneous or traumatic
Annualized bleeding rate (ABR) by location of bleed
ABR by location of bleed such as joint, muscle, internal, or skin/mucosa
Percentage of participants who maintain FVIII activity above prespecified levels
Number of injection and dose of BIVV001 to treat a bleeding episode
Percentage of bleeding episodes treated with a single injection of BIVV001
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.
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
Total annualized BIVV001 consumption
Annualized Joint Bleeding Rate (AJBR)
Target joint resolution
Target joint resolution at week 52, based on ISTH criteria.
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.
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)
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)
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
Number of injections and dose to maintain hemostasis during perioperative period for major surgery
Total BIVV001 consumption during perioperative period for major surgery
Number of blood component transfusions used during perioperative period for major surgery
Type of blood component transfusions used during perioperative period for major surgery
Estimated blood loss during perioperative period for major surgery
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)
Number of participants with occurrence of embolic and thrombotic events
PK parameter: Maximum activity (Cmax)
PK parameter: Elimination half-life (t1/2)
PK parameter: Total clearance (CL)
PK parameter: Total clearance at steady state (CLss)
PK parameter:dose-normalized area under the activity-time curve (DNAUC)
PK parameter: Area under the activity time curve (AUC)
PK parameter: Volume of distribution at steady state (Vss)
PK parameter: Mean residence time (MRT)
PK parameter: Incremental recovery (IR)
PK parameter: Trough activity (Ctrough)
PK parameter: Time above predefined FVIII activity levels

Full Information

First Posted
February 13, 2021
Last Updated
May 3, 2023
Sponsor
Bioverativ, a Sanofi company
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1. Study Identification

Unique Protocol Identification Number
NCT04759131
Brief Title
Safety, Efficacy and PK of BIVV001 in Pediatric Patients With Hemophilia A
Acronym
XTEND-Kids
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

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
February 19, 2021 (Actual)
Primary Completion Date
January 18, 2023 (Actual)
Study Completion Date
January 18, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bioverativ, a Sanofi company

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia A

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
75 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Prophylaxis
Arm Type
Experimental
Arm Description
Participants will receive weekly dose of BIVV001 for 52 weeks.
Intervention Type
Drug
Intervention Name(s)
efanesoctocog alfa (BIVV001)
Intervention Description
Pharmaceutical form:solution for injection Route of administration: Intravenous
Primary Outcome Measure Information:
Title
Occurrence of inhibitor development
Description
The occurrence of inhibitor development (neutralizing antibodies directed against factor VIII [FVIII]) as determined via the Nijmegen modified Bethesda assay
Time Frame
baseline to 52 weeks
Secondary Outcome Measure Information:
Title
Annualized bleeding rate (ABR) levels
Description
Annualized bleeding rate (ABR) for treated, for untreated, for all bleeding episodes.
Time Frame
baseline to week 52
Title
Annualized bleeding rate (ABR) by type of bleed
Description
ABR by type of bleed such as spontaneous or traumatic
Time Frame
baseline to week 52
Title
Annualized bleeding rate (ABR) by location of bleed
Description
ABR by location of bleed such as joint, muscle, internal, or skin/mucosa
Time Frame
baseline to week 52
Title
Percentage of participants who maintain FVIII activity above prespecified levels
Time Frame
baseline to week 52
Title
Number of injection and dose of BIVV001 to treat a bleeding episode
Time Frame
baseline to week 52
Title
Percentage of bleeding episodes treated with a single injection of BIVV001
Time Frame
baseline to week 52
Title
Assessment of response to BIVV001 treatment of individual bleeding episodes
Description
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
52 weeks
Title
Physician's global assessment of the participant's response based on BIVV001 treatment
Description
Physician's global assessment (PGA) of participant's response to BIVV001 treatment based on a 4-point response scale
Time Frame
baseline to week 52
Title
Total annualized BIVV001 consumption
Time Frame
baseline to week 52
Title
Annualized Joint Bleeding Rate (AJBR)
Time Frame
baseline to week 52
Title
Target joint resolution
Description
Target joint resolution at week 52, based on ISTH criteria.
Time Frame
At week 52
Title
Change in Hemophilia Joint Health Score (HJHS) total score and domain scores
Description
Change from baseline to week 52 in total score and domain scores (eg, swelling and strength) assessed by the HJHS.
Time Frame
baseline to week 52
Title
Changes in Haemophilia Quality of Life Questionnaire for Children (Haemo-QoL) total score
Description
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)
Time Frame
baseline to week 52
Title
Changes in Haemophilia Quality of Life Questionnaire for Children (Haemo-QoL) physical health domain scores from
Description
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)
Time Frame
baseline to week 52
Title
Investigators' or Surgeons' assessment of participant's hemostatic response to BIVV001 treatment
Description
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 week 52
Title
Number of injections and dose to maintain hemostasis during perioperative period for major surgery
Time Frame
baseline to week 52
Title
Total BIVV001 consumption during perioperative period for major surgery
Time Frame
baseline to week 52
Title
Number of blood component transfusions used during perioperative period for major surgery
Time Frame
baseline to week 52
Title
Type of blood component transfusions used during perioperative period for major surgery
Time Frame
baseline to week 52
Title
Estimated blood loss during perioperative period for major surgery
Time Frame
baseline to week 52
Title
Number of participants with occurence of adverse events (AEs) and serious adverse events (SAEs)
Description
Participants with ocurrence of adverse events (AEs) and serious adverse events (SAEs)
Time Frame
baseline to week 52
Title
Number of participants with occurrence of embolic and thrombotic events
Time Frame
baseline to week 52
Title
PK parameter: Maximum activity (Cmax)
Time Frame
baseline to week 52
Title
PK parameter: Elimination half-life (t1/2)
Time Frame
baseline (day 1)
Title
PK parameter: Total clearance (CL)
Time Frame
baseline (day 1)
Title
PK parameter: Total clearance at steady state (CLss)
Time Frame
baseline (day 1)
Title
PK parameter:dose-normalized area under the activity-time curve (DNAUC)
Time Frame
baseline (day 1)
Title
PK parameter: Area under the activity time curve (AUC)
Time Frame
baseline (day 1)
Title
PK parameter: Volume of distribution at steady state (Vss)
Time Frame
baseline (day 1)
Title
PK parameter: Mean residence time (MRT)
Time Frame
baseline (day 1)
Title
PK parameter: Incremental recovery (IR)
Time Frame
baseline to week 52
Title
PK parameter: Trough activity (Ctrough)
Time Frame
baseline to week 52
Title
PK parameter: Time above predefined FVIII activity levels
Time Frame
baseline (day 1)

10. Eligibility

Sex
Male
Maximum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
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 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Children's Hospital Los Angeles-Site Number:8400006
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
University of Florida-Site Number:8400009
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Children's Healthcare of Atlanta-Site Number:8400019
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Rush University Medical Center-Site Number:8400001
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612-3833
Country
United States
Facility Name
University of Iowa Hospitals and Clinics-Site Number:8400002
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
NY Presbyterian - Weill Cornell Medical Center-Site Number:8400020
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
East Carolina University/Brody Medical Sciences Building-Site Number:8400015
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27834
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center-Site Number:8400008
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45206
Country
United States
Facility Name
Childrens Hospital Of Columbus-Site Number:8400012
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Children's Hospital Of Wisconsin-Site Number:8400005
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226-0509
Country
United States
Facility Name
Investigational Site Number :0360001
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Investigational Site Number :0360002
City
South Brisbane
State/Province
Queensland
ZIP/Postal Code
4101
Country
Australia
Facility Name
Investigational Site Number :1240004
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 3Z5
Country
Canada
Facility Name
Investigational Site Number :1240003
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 4G5
Country
Canada
Facility Name
Investigational Site Number :1240002
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L1
Country
Canada
Facility Name
Investigational Site Number :1240001
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
Facility Name
Investigational Site Number :2500004
City
Bron
ZIP/Postal Code
69500
Country
France
Facility Name
Investigational Site Number :2500001
City
Kremlin Bicetre
ZIP/Postal Code
94275
Country
France
Facility Name
Investigational Site Number :2500003
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Investigational Site Number :2760001
City
Frankfurt am Main
ZIP/Postal Code
60590
Country
Germany
Facility Name
Investigational Site Number :2760002
City
München
ZIP/Postal Code
80337
Country
Germany
Facility Name
Investigational Site Number :3480005
City
Pécs
ZIP/Postal Code
7623
Country
Hungary
Facility Name
Investigational Site Number :3720001
City
Dublin
ZIP/Postal Code
D12 N512
Country
Ireland
Facility Name
Investigational Site Number :3800001
City
Milano
ZIP/Postal Code
20121
Country
Italy
Facility Name
Investigational Site Number :3800002
City
Napoli
ZIP/Postal Code
80123
Country
Italy
Facility Name
Investigational Site Number :5280002
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
Investigational Site Number :5280001
City
Utrecht
ZIP/Postal Code
3584 CX
Country
Netherlands
Facility Name
Investigational Site Number :7240002
City
Esplugues de Llobregat
State/Province
Catalunya [Cataluña]
ZIP/Postal Code
08950
Country
Spain
Facility Name
Investigational Site Number :7240001
City
Madrid
State/Province
Madrid, Comunidad De
ZIP/Postal Code
28046
Country
Spain
Facility Name
Investigational Site Number :7520001
City
Malmö
ZIP/Postal Code
20502
Country
Sweden
Facility Name
Investigational Site Number :7560001
City
Zürich
ZIP/Postal Code
8032
Country
Switzerland
Facility Name
Investigational Site Number :1580001
City
Taichung
ZIP/Postal Code
402
Country
Taiwan
Facility Name
Investigational Site Number :1580003
City
Taichung
ZIP/Postal Code
407
Country
Taiwan
Facility Name
Investigational Site Number :1580002
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Facility Name
Investigational Site Number :1580004
City
Taipei
ZIP/Postal Code
11031
Country
Taiwan
Facility Name
Investigational Site Number :7920004
City
Antalya
ZIP/Postal Code
07059
Country
Turkey
Facility Name
Investigational Site Number :7920001
City
Istanbul
ZIP/Postal Code
34390
Country
Turkey
Facility Name
Investigational Site Number :7920003
City
Izmir
ZIP/Postal Code
TR-35100
Country
Turkey
Facility Name
Investigational Site Number :8260003
City
Birmingham
ZIP/Postal Code
B4 6NH
Country
United Kingdom
Facility Name
Investigational Site Number :8260001
City
London
ZIP/Postal Code
WC1N3JH
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

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

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