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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

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
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04759131