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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04161495




Registration number
NCT04161495
Ethics application status
Date submitted
5/11/2019
Date registered
13/11/2019
Date last updated
24/05/2023

Titles & IDs
Public title
A Phase 3 Open-label Interventional Study of Intravenous Recombinant Coagulation Factor VIII Fc-von Willebrand Factor-XTEN Fusion Protein, Efanesoctocog Alfa (BIVV001), in Patients With Severe 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 Patients =12 Years of Age With Severe Hemophilia A
Secondary ID [1] 0 0
2019-002023-15
Secondary ID [2] 0 0
EFC16293
Universal Trial Number (UTN)
Trial acronym
XTEND-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Factor VIII Deficiency 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
Other interventions - efanesoctocog alfa (BIVV001)

Experimental: Arm A: Prophylaxis - Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 international units per kilogram (IU/kg) intravenous (IV) injection once-weekly (QW) for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis [OBS16221]) in the outcome measure analysis.

Experimental: Arm B: On-Demand Then Prophylaxis - Participants who were on an on-demand treatment regimen with a FVIII product prior to study EFC16293, including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection as an on-demand treatment (as needed for the treatment of bleeding episodes) from Week 1 to Week 26 in current study. At Week 26, participants in Arm B were switched to prophylaxis treatment, and received BIVV001 50 IU/kg, IV injection QW until Week 52.


Other interventions: efanesoctocog alfa (BIVV001)
Pharmaceutical form: solution for injection Route of administration: IV injection

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Estimated Annualized Bleeding Rate (ABR) in Arm A: Prophylaxis
Timepoint [1] 0 0
Baseline to Week 52
Primary outcome [2] 0 0
Observed Annualized Bleeding Rate in Arm A: Prophylaxis
Timepoint [2] 0 0
Baseline to Week 52
Secondary outcome [1] 0 0
Estimated Annualized Bleeding Rate During the Efficacy Period in Arm A: Prophylaxis - Non-inferiority Analysis
Timepoint [1] 0 0
Historical prophylaxis: From 6 months (prior to entry into study EFC16293) until the day before enrollment in EFC16293; BIVV001 prophylaxis: Baseline up to Week 52 of current study EFC16293
Secondary outcome [2] 0 0
Observed Annualized Bleeding Rate During the Efficacy Period in Prophylaxis - Non-inferiority Analysis
Timepoint [2] 0 0
Historical prophylaxis: From 6 months (prior to entry into study EFC16293) until the day before enrollment in EFC16293; BIVV001 Prophylaxis: Baseline up to Week 52 of current study EFC16293
Secondary outcome [3] 0 0
Estimated Annualized Bleeding Rate During the Efficacy Period in Arm A: Prophylaxis - Superiority Analysis
Timepoint [3] 0 0
Historical Prophylaxis: From 6 months (prior to entry into study EFC16293) until the day before enrollment in EFC16293; BIVV001 Prophylaxis: Baseline up to Week 52 of current study EFC16293
Secondary outcome [4] 0 0
Observed Annualized Bleeding Rate During the Efficacy Period in Arm A: Prophylaxis - Superiority Analysis
Timepoint [4] 0 0
Historical Prophylaxis: From 6 months (prior to entry into study EFC16293) until the day before enrollment in EFC16293; BIVV001 Prophylaxis: Baseline up to Week 52 of current study EFC16293
Secondary outcome [5] 0 0
Change From Baseline in Hemophilia-specific Health-related Quality of Life Questionnaire for Adults (Haem-A-QOL) Physical Health Domain Score at Week 52 in Arm A: Prophylaxis
Timepoint [5] 0 0
Baseline, Week 52
Secondary outcome [6] 0 0
Change From Baseline in Patient Reported Outcomes Measurements Information Systems (PROMIS) Pain Intensity 3a Score at Week 52 in Arm A: Prophylaxis
Timepoint [6] 0 0
Baseline, Week 52
Secondary outcome [7] 0 0
Change From Baseline in Hemophilia Joint Health Score (HJHS) Total Score at Week 52 in Arm A: Prophylaxis
Timepoint [7] 0 0
Baseline, Week 52
Secondary outcome [8] 0 0
Annualized Bleeding Rate by Type of Bleed (Spontaneous, Traumatic and Unknown Type)
Timepoint [8] 0 0
Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52
Secondary outcome [9] 0 0
Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal and Skin/Mucosa)
Timepoint [9] 0 0
Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52
Secondary outcome [10] 0 0
Annualized Bleeding Rate for All Bleeding Episodes
Timepoint [10] 0 0
Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52
Secondary outcome [11] 0 0
Annualized Bleeding Rate: Intra-participant Comparison of Arm B Participants
Timepoint [11] 0 0
Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52
Secondary outcome [12] 0 0
Percentage of Participants Achieving Factor VIII (FVIII) Activity Levels Above 1%, 5%, 10%, 15%, and 20% in Arm A: Prophylaxis
Timepoint [12] 0 0
Baseline to Week 52
Secondary outcome [13] 0 0
Number of Injections of BIVV001 Required to Treat a Bleeding Episode
Timepoint [13] 0 0
Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52
Secondary outcome [14] 0 0
Total Dose of BIVV001 Required to Treat Bleeding Episode
Timepoint [14] 0 0
Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52
Secondary outcome [15] 0 0
Percentage of Bleeding Episodes Treated With a Single Injection of BIVV001
Timepoint [15] 0 0
Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52
Secondary outcome [16] 0 0
Percentage of Participants With Response to BIVV001 Treatment Based on the International Society on Thrombosis and Haemostasis (ISTH) 4-point Response Scale
Timepoint [16] 0 0
Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52
Secondary outcome [17] 0 0
Physicians' Global Assessment of Participant's Response to BIVV001 Treatment
Timepoint [17] 0 0
Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52
Secondary outcome [18] 0 0
Total Annualized BIVV001 Consumption Per Participant
Timepoint [18] 0 0
Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52
Secondary outcome [19] 0 0
Change From Baseline in Hemophilia Joint Health Score (HJHS) Domain Score at Week 52 in Arm A: Prophylaxis
Timepoint [19] 0 0
Baseline, Week 52
Secondary outcome [20] 0 0
Estimated Annualized Joint Bleeding Rate (AJBR)
Timepoint [20] 0 0
Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52
Secondary outcome [21] 0 0
Observed Annualized Joint Bleeding Rate (AJBR)
Timepoint [21] 0 0
Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52
Secondary outcome [22] 0 0
Total Number of Target Joint Resolved in Participants at Week 52 in Arm A: Prophylaxis
Timepoint [22] 0 0
Week 52
Secondary outcome [23] 0 0
Change From Baseline in Hemophilia-specific Health-related Quality of Life Questionnaire for Adults Total Score at Week 52 in Arm A: Prophylaxis
Timepoint [23] 0 0
Baseline, Week 52
Secondary outcome [24] 0 0
Change From Baseline in Patient Reported Outcomes Measurements Information Systems Short Form (PROMIS-SF) Physical Function (PF) 6b at Week 52 in Arm A: Prophylaxis
Timepoint [24] 0 0
Baseline, Week 52
Secondary outcome [25] 0 0
Investigators' or Surgeons' Assessment of Participant's Hemostatic Response to BIVV001 Treatment
Timepoint [25] 0 0
Baseline to Week 52
Secondary outcome [26] 0 0
Number of Injections Per Surgery Required to Maintain Hemostasis During Perioperative Period for Major Surgery
Timepoint [26] 0 0
During the perioperative period (any time during Baseline up to Week 52)
Secondary outcome [27] 0 0
Total Dose Required to Maintain Hemostasis From Day -1 to Day 0 During Perioperative Period for Major Surgery
Timepoint [27] 0 0
Day -1 to Day 0 (day of surgery)
Secondary outcome [28] 0 0
Total BIVV001 Consumption From Day -1 to 14 During Perioperative Period for Major Surgery
Timepoint [28] 0 0
Day -1 to Day 14
Secondary outcome [29] 0 0
Number of Blood Component Transfusions Used 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
Type 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
Estimated Blood Loss During Major Surgery
Timepoint [31] 0 0
Day 0 (i.e., day of surgery)
Secondary outcome [32] 0 0
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAE)
Timepoint [32] 0 0
Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 up to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55)
Secondary outcome [33] 0 0
Number of Participants With Neutralizing Antibodies (Development of Inhibitors) Directed Against Factor VIII
Timepoint [33] 0 0
Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52
Secondary outcome [34] 0 0
Number of Participants With Occurrence of Embolic and Thrombotic Events
Timepoint [34] 0 0
Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52
Secondary outcome [35] 0 0
Pharmacokinetics (PK): Maximum FVIII Activity (Cmax)
Timepoint [35] 0 0
Baseline (15 minutes post-dose on Day 1) and 15 minutes post-dose on Week 52
Secondary outcome [36] 0 0
Pharmacokinetics: Elimination Half-life (t1/2z)
Timepoint [36] 0 0
pre-dose, 0.25, 3, 24, 72, 168, 240 and 336 hours post-dose on Day 1 (Baseline); pre-dose, 0.25, 3, 24, 72, 168, 240, and 336 hours post-dose on Week 26
Secondary outcome [37] 0 0
Pharmacokinetics: Clearance (CL)
Timepoint [37] 0 0
Pre-dose, 0.25, 3, 24, 72, 168, 240 and 336 hours post-dose on Day 1 (Baseline)
Secondary outcome [38] 0 0
Pharmacokinetics: Total Clearance at Steady State (CLss)
Timepoint [38] 0 0
Pre-dose, 0.25, 3, 24, 72, 168, 240, and 336 hours post-dose on Week 26
Secondary outcome [39] 0 0
Pharmacokinetics: Accumulation Index (AI)
Timepoint [39] 0 0
Pre-dose, 0.25, 3, 24, 72, 168, 240, and 336 hours post-dose on Week 26
Secondary outcome [40] 0 0
Pharmacokinetics: Area Under the Plasma FVIII Activity Versus Time Curve (AUC0-tau)
Timepoint [40] 0 0
Pre-dose, 0.25, 3, 24, 72, 168, 240 and 336 hours post-dose on Day 1 (Baseline); pre-dose, 0.25, 3, 24, 72, 168, 240, and 336 hours post-dose on Week 26 (Day 183)
Secondary outcome [41] 0 0
Pharmacokinetics: Volume of Distribution at Steady State (Vss)
Timepoint [41] 0 0
Pre-dose, 0.25, 3, 24, 72, 168, 240 and 336 hours post-dose on Day 1 (Baseline); pre-dose, 0.25, 3, 24, 72, 168, 240, and 336 hours post-dose on Week 26 (Day 183)
Secondary outcome [42] 0 0
Pharmacokinetics: Mean Residence Time (MRT)
Timepoint [42] 0 0
Pre-dose, 0.25, 3, 24, 72, 168, 240 and 336 hours post-dose on Day 1 (Baseline); pre-dose, 0.25, 3, 24, 72, 168, 240, and 336 hours post-dose on Week 26 (Day 183)
Secondary outcome [43] 0 0
Pharmacokinetics: Incremental Recovery (IR)
Timepoint [43] 0 0
Pre-dose, 0.25 hours post-dose on Day 1 (Baseline); pre-dose, 0.25 hours post-dose on Week 26 (Day 183)
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: Time Above Predefined (10 and 40%) FVIII Activity Levels
Timepoint [45] 0 0
Pre-dose and 0.25, 3, 24, 72, 168, 240 and 336 hours post-dose on Day 1 (Baseline)

Eligibility
Key inclusion criteria
Inclusion criteria:

- Participant, male or female, must be equal to or greater than 12 years of age
inclusive, at the time of signing the informed consent.

- Severe hemophilia A, defined as less than (<) 1 international units per deciliter
(IU/dL) (<1 percent [%]) endogenous FVIII activity 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.

- Current regimen included one of the following:

- Prophylactic treatment regimen with a FVIII product or prophylactic emicizumab
therapy for at least 6 months during the previous 12 months. Appropriate washout
time needs to be taken into account.

- On-demand regimen with a FVIII product with a history of at least 12 bleeding
episodes in the previous 12 months or at least 6 bleeding episodes in the
previous 6 months prior to study enrollment.

- On-demand participant was accepted to move to a prophylaxis treatment regimen after
26-week on-demand period.

- Willingness and ability of the participant or surrogate (a caregiver or a family
member greater than or equal to [>=] 18 years of age) to complete training in the use
of the study electronic Patient Diary (ePD) and to use the ePD throughout the study.

- Ability of the participant or his or her legally authorized representative (eg.,
parent or legal guardian) to understand the purpose and risks of the study, willing
and able to comply with study requirements and provide signed and dated informed
consent or assent (as applicable) and authorization to use protected health
information in accordance with national and local participant privacy regulations.
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

- Clinically significant liver disease.

- Serious active bacterial or viral infection (other than chronic hepatitis or HIV)
present within 30 days of screening.

- Other known coagulation disorder(s) in addition to hemophilia A.

- History of hypersensitivity or anaphylaxis associated with any FVIII product.

- Positive inhibitor results, defined as >=0.6 Bethesda unit per milliliter (BU/mL) at
screening. History of a positive inhibitor test defined as >=0.6 BU/mL. Family history
of inhibitors would not exclude the participant.

- Use of Emicizumab within the 20 weeks prior to screening.

- Major surgery within 8 weeks prior to 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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Investigational Site Number 121 - Perth
Recruitment hospital [2] 0 0
Investigational Site Number 122 - Sydney
Recruitment postcode(s) [1] 0 0
- Perth
Recruitment postcode(s) [2] 0 0
- Sydney
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
Michigan
Country [4] 0 0
United States of America
State/province [4] 0 0
Nevada
Country [5] 0 0
United States of America
State/province [5] 0 0
Washington
Country [6] 0 0
Argentina
State/province [6] 0 0
Buenos Aires
Country [7] 0 0
Argentina
State/province [7] 0 0
Mendoza
Country [8] 0 0
Belgium
State/province [8] 0 0
Brussels
Country [9] 0 0
Brazil
State/province [9] 0 0
Campinas
Country [10] 0 0
Bulgaria
State/province [10] 0 0
Plovdiv
Country [11] 0 0
Bulgaria
State/province [11] 0 0
Sofia
Country [12] 0 0
Canada
State/province [12] 0 0
Hamilton
Country [13] 0 0
France
State/province [13] 0 0
Brest
Country [14] 0 0
France
State/province [14] 0 0
Lille
Country [15] 0 0
France
State/province [15] 0 0
Lyon
Country [16] 0 0
France
State/province [16] 0 0
Marseille
Country [17] 0 0
Germany
State/province [17] 0 0
Berlin
Country [18] 0 0
Germany
State/province [18] 0 0
Bonn
Country [19] 0 0
Germany
State/province [19] 0 0
Frankfurt
Country [20] 0 0
Greece
State/province [20] 0 0
Athens
Country [21] 0 0
Hungary
State/province [21] 0 0
Budapest
Country [22] 0 0
Hungary
State/province [22] 0 0
Debrecen
Country [23] 0 0
Italy
State/province [23] 0 0
Milan
Country [24] 0 0
Italy
State/province [24] 0 0
Vicenza
Country [25] 0 0
Japan
State/province [25] 0 0
Kawasaki
Country [26] 0 0
Japan
State/province [26] 0 0
Kitakyushu
Country [27] 0 0
Japan
State/province [27] 0 0
Nagoya
Country [28] 0 0
Japan
State/province [28] 0 0
Nara
Country [29] 0 0
Japan
State/province [29] 0 0
Tokyo
Country [30] 0 0
Korea, Republic of
State/province [30] 0 0
Daegu
Country [31] 0 0
Korea, Republic of
State/province [31] 0 0
Seoul
Country [32] 0 0
Mexico
State/province [32] 0 0
Durango
Country [33] 0 0
Netherlands
State/province [33] 0 0
Utrecht
Country [34] 0 0
Spain
State/province [34] 0 0
Madrid
Country [35] 0 0
Taiwan
State/province [35] 0 0
Chang Hua
Country [36] 0 0
Taiwan
State/province [36] 0 0
Taipei
Country [37] 0 0
United Kingdom
State/province [37] 0 0
Basingstoke
Country [38] 0 0
United Kingdom
State/province [38] 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 efficacy of BIVV001 as a prophylaxis treatment in prophylaxis treatment
arm.

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 the 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 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 based on the 1-stage activated partial
thromboplastin time (aPTT) and 2-stage chromogenic coagulation factor VIII (FVIII)
activity assays.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04161495
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/ct2/show/NCT04161495