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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04759131




Registration number
NCT04759131
Ethics application status
Date submitted
13/02/2021
Date registered
18/02/2021
Date last updated
13/02/2024

Titles & IDs
Public title
Safety, Efficacy and PK of BIVV001 in Pediatric Patients With Hemophilia A
Scientific 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
Secondary ID [1] 0 0
2020-000769-18
Secondary ID [2] 0 0
EFC16295
Universal Trial Number (UTN)
Trial acronym
XTEND-Kids
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hemophilia A 0 0
Condition category
Condition code
Blood 0 0 0 0
Clotting disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - efanesoctocog alfa (BIVV001)

Experimental: BIVV001: Participants aged <6 Years - Participants aged less than (\<) 6 years received BIVV001 at a dose of 50 international units per kilogram (IU/kg) intravenous (IV) injection once-weekly (QW) prophylaxis for 52 weeks.

Experimental: BIVV001: Participants aged 6 to <12 Years - Participants aged 6 to \<12 years received BIVV001 at a dose of 50 IU/kg IV injection QW prophylaxis for 52 weeks.


Treatment: Drugs: efanesoctocog alfa (BIVV001)
Pharmaceutical form: solution for injection Route of administration: IV
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Neutralising Antibodies (Development of Inhibitors) Directed Against Factor VIII
Timepoint [1] 0 0
Baseline up to Week 52
Secondary outcome [1] 0 0
Annualized Bleeding Rate (ABR): For Treated Bleeds
Timepoint [1] 0 0
Baseline up to Week 52
Secondary outcome [2] 0 0
Sensitivity Analysis: Annualized Bleeding Rate: For Treated Bleeds
Timepoint [2] 0 0
Baseline up to Week 52
Secondary outcome [3] 0 0
Annualized Bleeding Rate for All Bleeding Episodes
Timepoint [3] 0 0
Baseline up to Week 52
Secondary outcome [4] 0 0
Sensitivity Analysis: Annualized Bleeding Rate for All Bleeding Episodes
Timepoint [4] 0 0
Baseline up to Week 52
Secondary outcome [5] 0 0
Annualized Bleeding Rate by Type of Bleed (Spontaneous, Traumatic and Unknown Type)
Timepoint [5] 0 0
Baseline up to Week 52
Secondary outcome [6] 0 0
Sensitivity Analysis: Annualized Bleeding Rate by Type of Bleed (Spontaneous, Traumatic and Unknown Type)
Timepoint [6] 0 0
Baseline up to Week 52
Secondary outcome [7] 0 0
Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal and Skin/Mucosa)
Timepoint [7] 0 0
Baseline up to Week 52
Secondary outcome [8] 0 0
Sensitivity Analysis: Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal and Skin/Mucosa)
Timepoint [8] 0 0
Baseline up to Week 52
Secondary outcome [9] 0 0
Percentage of Participants Achieving FVIII Activity Levels Above 1%, 3%, 5%, 10%, 15%, and 20%
Timepoint [9] 0 0
Baseline up to Week 52
Secondary outcome [10] 0 0
Number of Injections of BIVV001 Required to Treat a Bleeding Episode
Timepoint [10] 0 0
Baseline up to Week 52
Secondary outcome [11] 0 0
Sensitivity Analysis: Number of Injections of BIVV001 Required to Treat a Bleeding Episode
Timepoint [11] 0 0
Baseline up to Week 52
Secondary outcome [12] 0 0
Percentage of Bleeding Episodes Treated With a Single Injection of BIVV001
Timepoint [12] 0 0
Baseline up to Week 52
Secondary outcome [13] 0 0
Sensitivity Analysis: Percentage of Bleeding Episodes Treated With a Single Injection of BIVV001
Timepoint [13] 0 0
Baseline up to Week 52
Secondary outcome [14] 0 0
Total Dose of BIVV001 Required to Treat a Bleeding Episode
Timepoint [14] 0 0
Baseline up to Week 52
Secondary outcome [15] 0 0
Sensitivity Analysis: Total Dose of BIVV001 Required to Treat a Bleeding Episode
Timepoint [15] 0 0
Baseline up to Week 52
Secondary outcome [16] 0 0
Physicians' Global Assessment (PGA) of Participant's Response to BIVV001 Treatment Based on a 4-point Response Scale
Timepoint [16] 0 0
Week 13 and Week 52/End of study (EOS)/Early termination (ET)
Secondary outcome [17] 0 0
Participant's Response to BIVV001 Treatment Based on the International Society on Thrombosis and Haemostasis (ISTH) 4-point Response Scale
Timepoint [17] 0 0
Baseline up to Week 52
Secondary outcome [18] 0 0
Total Annualized BIVV001 Consumption Per Participant
Timepoint [18] 0 0
Baseline up to Week 52
Secondary outcome [19] 0 0
Annualized Joint Bleeding Rate (AJBR)
Timepoint [19] 0 0
Baseline up to Week 52
Secondary outcome [20] 0 0
Sensitivity Analysis: Annualized Joint Bleeding Rate (AJBR)
Timepoint [20] 0 0
Baseline up to Week 52
Secondary outcome [21] 0 0
Change From Baseline in Hemophilia Joint Health Score Domain Score at Week 52
Timepoint [21] 0 0
Baseline, Week 52
Secondary outcome [22] 0 0
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)
Timepoint [22] 0 0
Baseline, Week 52
Secondary outcome [23] 0 0
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
Timepoint [23] 0 0
Baseline, Week 52
Secondary outcome [24] 0 0
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)
Timepoint [24] 0 0
Baseline, Week 52
Secondary outcome [25] 0 0
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
Timepoint [25] 0 0
Baseline, Week 52
Secondary outcome [26] 0 0
Total Number of Target Joints Resolved in Participants at Week 52
Timepoint [26] 0 0
Week 52
Secondary outcome [27] 0 0
Change From Baseline in Hemophilia Joint Health Score (HJHS) Total Score at Week 52
Timepoint [27] 0 0
Baseline, Week 52
Secondary outcome [28] 0 0
Investigators' or Surgeons' Assessment of Participant's Hemostatic Response to BIVV001 Treatment
Timepoint [28] 0 0
Baseline up to Week 52
Secondary outcome [29] 0 0
Number of Injections Per Surgery Required to Maintain Hemostasis During Perioperative Period for Major Surgery
Timepoint [29] 0 0
During the perioperative period (any time during Baseline up to Week 52)
Secondary outcome [30] 0 0
Number of Blood Component Transfusions Used During Perioperative Period for Major Surgery
Timepoint [30] 0 0
During the perioperative period (any time during Baseline up to Week 52)
Secondary outcome [31] 0 0
Total BIVV001 Consumption From Day -1 to 14 During Perioperative Period for Major Surgery
Timepoint [31] 0 0
Day -1 to Day 14
Secondary outcome [32] 0 0
Type of Blood Component Transfusions Used During Perioperative Period for Major Surgery
Timepoint [32] 0 0
During the perioperative period (any time during Baseline up to Week 52)
Secondary outcome [33] 0 0
Total Dose Required to Maintain Hemostasis From Day -1 to Day 0 During Perioperative Period for Major Surgery
Timepoint [33] 0 0
Day -1 to Day 0 (day of surgery)
Secondary outcome [34] 0 0
Estimated Blood Loss During Major Surgery
Timepoint [34] 0 0
Day 0 (i.e., day of surgery)
Secondary outcome [35] 0 0
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse (TESAEs)
Timepoint [35] 0 0
From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55)
Secondary outcome [36] 0 0
Number of Participants With Occurrence of Embolic and Thrombotic Events
Timepoint [36] 0 0
Baseline up to Week 52
Secondary outcome [37] 0 0
Pharmacokinetics (PK): Maximum FVIII Activity (Cmax)
Timepoint [37] 0 0
Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1
Secondary outcome [38] 0 0
Pharmacokinetics: Clearance (CL)
Timepoint [38] 0 0
Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1
Secondary outcome [39] 0 0
Pharmacokinetics: Volume of Distribution at Steady State (Vss)
Timepoint [39] 0 0
Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1
Secondary outcome [40] 0 0
Pharmacokinetics: Elimination Half-life (t1/2z)
Timepoint [40] 0 0
Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1
Secondary outcome [41] 0 0
Pharmacokinetics: Area Under the Plasma FVIII Activity Versus Time Curve (AUC0-tau)
Timepoint [41] 0 0
Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1
Secondary outcome [42] 0 0
Pharmacokinetics: Total Clearance at Steady State (CLss)
Timepoint [42] 0 0
0 hour - 168 hour at week 26, 39 or 52
Secondary outcome [43] 0 0
Pharmacokinetics: Incremental Recovery (IR)
Timepoint [43] 0 0
Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1
Secondary outcome [44] 0 0
Pharmacokinetics: Trough Concentration for BIVV001 (Ctrough)
Timepoint [44] 0 0
Pre-dose at Baseline (Day 1) and Week 52
Secondary outcome [45] 0 0
Pharmacokinetics: Mean Residence Time (MRT)
Timepoint [45] 0 0
Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1
Secondary outcome [46] 0 0
Time Above Predefined (10% and 40%) FVIII Activity Levels
Timepoint [46] 0 0
Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1
Secondary outcome [47] 0 0
Pharmacokinetics: Dose-normalized Area Under the Activity-time Curve (DNAUC0-tau)
Timepoint [47] 0 0
Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1

Eligibility
Key inclusion 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.
Minimum age
No limit
Maximum age
11 Years
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/02/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
18/01/2023
Sample size
Target
Accrual to date
Final
74
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
Investigational Site Number :0360001 - Westmead
Recruitment hospital [2] 0 0
Investigational Site Number :0360002 - South Brisbane
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Iowa
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Wisconsin
Country [10] 0 0
Canada
State/province [10] 0 0
Ontario
Country [11] 0 0
France
State/province [11] 0 0
Bron
Country [12] 0 0
France
State/province [12] 0 0
Kremlin Bicetre
Country [13] 0 0
France
State/province [13] 0 0
Lille
Country [14] 0 0
Germany
State/province [14] 0 0
Frankfurt am Main
Country [15] 0 0
Germany
State/province [15] 0 0
München
Country [16] 0 0
Hungary
State/province [16] 0 0
Pécs
Country [17] 0 0
Ireland
State/province [17] 0 0
Dublin
Country [18] 0 0
Italy
State/province [18] 0 0
Milano
Country [19] 0 0
Italy
State/province [19] 0 0
Napoli
Country [20] 0 0
Netherlands
State/province [20] 0 0
Amsterdam
Country [21] 0 0
Netherlands
State/province [21] 0 0
Utrecht
Country [22] 0 0
Spain
State/province [22] 0 0
Catalunya [Cataluña]
Country [23] 0 0
Spain
State/province [23] 0 0
Madrid, Comunidad De
Country [24] 0 0
Sweden
State/province [24] 0 0
Malmö
Country [25] 0 0
Switzerland
State/province [25] 0 0
Zürich
Country [26] 0 0
Taiwan
State/province [26] 0 0
Taichung
Country [27] 0 0
Taiwan
State/province [27] 0 0
Taipei
Country [28] 0 0
Turkey
State/province [28] 0 0
Antalya
Country [29] 0 0
Turkey
State/province [29] 0 0
Istanbul
Country [30] 0 0
Turkey
State/province [30] 0 0
Izmir
Country [31] 0 0
United Kingdom
State/province [31] 0 0
Birmingham
Country [32] 0 0
United Kingdom
State/province [32] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bioverativ, a Sanofi company
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT04759131
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04759131