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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04644575




Registration number
NCT04644575
Ethics application status
Date submitted
23/11/2020
Date registered
25/11/2020

Titles & IDs
Public title
Long-term Safety and Efficacy of Efanesoctocog Alfa (BIVV001) in Previously Treated Patients With Hemophilia A
Scientific title
A Phase 3 Open-label, Multicenter Study of the Long-term Safety and Efficacy of Intravenous Recombinant Coagulation Factor VIII Fc-von Willebrand Factor-XTEN Fusion Protein (rFVIIIFc-VWF-XTEN; BIVV001) in Previously Treated Patients With Severe Hemophilia A
Secondary ID [1] 0 0
U1111-1244-0517
Secondary ID [2] 0 0
LTS16294
Universal Trial Number (UTN)
Trial acronym
XTEND-ed
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: Arm A: Previously treated in BIVV001 study - This arm includes participants who have completed study EFC16293 or study EFC16295, participants who have completed Arm B or Arm C of this study (LTS16294) and roll over into Arm A, and participants who have completed any other potential BIVV001 study. Participants in this arm will continue receiving BIVV001 prophylaxis treatment once weekly (QW) for a total of 100 exposure days (EDs) cumulative from the parent study and this study. Participants will have the opportunity to continue in this study for up to 4 years, unless BIVV001 is commercially available in their applicable participating country.

Experimental: Arm B: Newly initiated (China Only) in BIVV001 - This arm includes Chinese participants of any age who will be newly initiated on BIVV001 prophylaxis treatment once-weekly (QW) for 52 weeks. After 52 weeks of treatment in this arm B, participants will be able to roll over into arm A.

Experimental: Arm C: Newly initiated in BIVV001 with planned major surgery - This arm includes participants of any age who will be newly initiated on BIVV001 prophylaxis treatment once-weekly (QW) and will undergo planned major surgery after at least 6 initial EDs with BIVV001, and within 26 weeks from Day 1. After 52 weeks of treatment in arm C, participants will be able to roll into arm A.


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

Outcomes
Primary outcome [1] 0 0
Number of participants with the occurrence of inhibitor development (neutralizing antibodies detected against factor VIII [FVIII])
Timepoint [1] 0 0
Baseline to month 48
Secondary outcome [1] 0 0
Annual bleeding rate (ABR)
Timepoint [1] 0 0
Baseline to month 48
Secondary outcome [2] 0 0
Annualized bleeding rate (ABR) by type of bleed
Timepoint [2] 0 0
Baseline to month 48
Secondary outcome [3] 0 0
Annualized bleeding rate (ABR) by location
Timepoint [3] 0 0
Baseline to month 48
Secondary outcome [4] 0 0
Percentage of patients who maintain factor VIII (FVIII) above prespecified activity levels
Timepoint [4] 0 0
Baseline to month 48
Secondary outcome [5] 0 0
Number of injections and dose of BIVV0001 to treat a bleeding episode
Timepoint [5] 0 0
Month 48
Secondary outcome [6] 0 0
Percentage of bleeding episode treated with a single injection of BIVV001
Timepoint [6] 0 0
Month 48
Secondary outcome [7] 0 0
Assessment of response to BIVV001 treatment of individual bleeding episodes
Timepoint [7] 0 0
Baseline to month 48
Secondary outcome [8] 0 0
Physician's global assessment (PGA) of participants response to BIVV001
Timepoint [8] 0 0
Baseline to month 48
Secondary outcome [9] 0 0
Total annualized BIVV001 consumption
Timepoint [9] 0 0
Baseline to month 48
Secondary outcome [10] 0 0
Annualized joint bleeding rate (AJBR)
Timepoint [10] 0 0
Baseline to month 48
Secondary outcome [11] 0 0
Target joint resolution
Timepoint [11] 0 0
Month 48
Secondary outcome [12] 0 0
Change from baseline in Hemophilia Joint Health Score (HJHS)
Timepoint [12] 0 0
Baseline to month 48
Secondary outcome [13] 0 0
Change from baseline in PROMIS-SF Physical Function
Timepoint [13] 0 0
Baseline to month 48
Secondary outcome [14] 0 0
Change from baseline in Haem-A-QoL total score and physical health score
Timepoint [14] 0 0
Baseline to month 48
Secondary outcome [15] 0 0
Change from baselin in Haemo-QoL total score and physical health score
Timepoint [15] 0 0
Baseline to month 48
Secondary outcome [16] 0 0
Number of participants with adverse events (AEs) and serious adverse events (SAEs)
Timepoint [16] 0 0
Baseline to month 48
Secondary outcome [17] 0 0
Number of participants with the occurrence of embolic and thrombotic events
Timepoint [17] 0 0
Baseline to month 48
Secondary outcome [18] 0 0
PK parameter: Maximum activity (Cmax)
Timepoint [18] 0 0
Baseline to week 52
Secondary outcome [19] 0 0
PK parameter: Elimination half-life (t1/2)
Timepoint [19] 0 0
Baseline to week 26
Secondary outcome [20] 0 0
PK parameter: Total clearance (CL)
Timepoint [20] 0 0
Baseline to week 26
Secondary outcome [21] 0 0
PK parameter: Total clearance at steady state (CLss)
Timepoint [21] 0 0
Baseline to week 26
Secondary outcome [22] 0 0
PK parameter: Accumulation index (AI)
Timepoint [22] 0 0
Baseline to week 26
Secondary outcome [23] 0 0
PK parameter: Area under the activity time curve (AUC)
Timepoint [23] 0 0
Baseline to week 26
Secondary outcome [24] 0 0
PK parameter: Volume of distribution at steady state (Vss)
Timepoint [24] 0 0
Baseline to week 26
Secondary outcome [25] 0 0
PK parameter: Mean residence time (MRT)
Timepoint [25] 0 0
Baseline to week 26
Secondary outcome [26] 0 0
PK parameter: Incremental recovery (IR)
Timepoint [26] 0 0
Baseline to week 52
Secondary outcome [27] 0 0
PK parameter: Trough activity (Ctrough)
Timepoint [27] 0 0
Baseline to week 52
Secondary outcome [28] 0 0
PK parameter: Time above FVIII activity levels
Timepoint [28] 0 0
Baseline to week 26
Secondary outcome [29] 0 0
Investigators' or Surgeons' assessment of participant's hemostatic response to BIVV001 treatment
Timepoint [29] 0 0
Baseline to month 48
Secondary outcome [30] 0 0
Number of injections and dose to maintain hemostasis during perioperative period for major surgery
Timepoint [30] 0 0
Baseline to month 48
Secondary outcome [31] 0 0
Total BIVV001 consumption during perioperative period for major surgery
Timepoint [31] 0 0
Baseline to month 48
Secondary outcome [32] 0 0
Number and type of blood component transfusions used during perioperative period for major surgery
Timepoint [32] 0 0
Baseline to month 48
Secondary outcome [33] 0 0
Estimated blood loss during perioperative period for major surgery
Timepoint [33] 0 0
Baseline to month 48

Eligibility
Key inclusion criteria
Inclusion criteria :

* For participants rolling over into Arm A

* Participants who have completed the studies EFC16923, EFC16925, Arm B or Arm C of the current study, or any other potential BIVV001 study.
* Male or Female
* For participants new to BIVV001 (Arm B and C)

* Participants who have severe hemophilia A, defined as <1 IU/dL (<1%) 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 EDs or 50 EDs for participants aged <6 years.
* Platelet count =100 000 cells/µL at screening.
* A participant known to be human immunodeficiency virus (HIV) antibody positive, either previously documented or identified from screening assessments, must have the following results prior to enrollment: CD4 lymphocyte count >200 cells/mm³ and viral load of <400 000 copies/mL
* Male
* Only for Arm B: Chinese participants
* Only for Arm C: planned major surgery within 6 months after Day 1.
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

* For participants rolling over into Arm A

* Positive inhibitor result, defined as =0.6 Bethesda units (BU)/mL.
* Participation in another study.
* For participants new to BIVV001 (Arm B and Arm C)

* Any concurrent clinically significant liver disease that, in the opinion of the Investigator, would make the participant unsuitable for enrollment. This may include, but is not limited to cirrhosis, portal hypertension, and acute hepatitis.
* Serious active bacterial, fungal, 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.
* 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 (FVIII) result, defined as =0.6 BU/mL at screening.
* Treatment with acetylsalicylic acid (ASA) or antiplatelet agents that are not nonsteroidal anti-inflammatory drugs (NSAIDs) within 2 weeks prior to screening.
* Treatment with NSAIDs greater than the maximum dose specified in the regional prescribing information within 2 weeks prior to screening.
* Systemic treatment within 12 weeks prior to Screening with chemotherapy and/or other immunosuppressive drugs (except for the treatment of hepatitis C virus [HCV] or HIV).
* Emicizumab use within the 20 weeks prior to screening.
* Major surgery within 8 weeks prior to screening.

The above information is not intended to contain all considerations relevant to a patient'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
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/02/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
15/01/2027
Actual
Sample size
Target
Accrual to date
Final
261
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
Investigational Site Number : 0360004 - Camperdown
Recruitment hospital [2] 0 0
Investigational Site Number : 0360001 - Westmead
Recruitment hospital [3] 0 0
Investigational Site Number : 0360002 - South Brisbane
Recruitment hospital [4] 0 0
Investigational Site Number : 0360003 - Murdoch
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
6961 - Murdoch
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
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Nevada
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Washington
Country [12] 0 0
United States of America
State/province [12] 0 0
Wisconsin
Country [13] 0 0
Argentina
State/province [13] 0 0
Ciudad De Buenos Aires
Country [14] 0 0
Argentina
State/province [14] 0 0
Mendoza
Country [15] 0 0
Argentina
State/province [15] 0 0
Buenos Aires
Country [16] 0 0
Belgium
State/province [16] 0 0
Sint-Lambrechts-Woluwe
Country [17] 0 0
Brazil
State/province [17] 0 0
São Paulo
Country [18] 0 0
Bulgaria
State/province [18] 0 0
Plovdiv
Country [19] 0 0
Bulgaria
State/province [19] 0 0
Sofia
Country [20] 0 0
Canada
State/province [20] 0 0
Ontario
Country [21] 0 0
China
State/province [21] 0 0
Beijing
Country [22] 0 0
China
State/province [22] 0 0
Guangzhou
Country [23] 0 0
China
State/province [23] 0 0
Hangzhou
Country [24] 0 0
China
State/province [24] 0 0
Jinan
Country [25] 0 0
China
State/province [25] 0 0
Kunming
Country [26] 0 0
China
State/province [26] 0 0
Lanzhou
Country [27] 0 0
China
State/province [27] 0 0
Suzhou
Country [28] 0 0
France
State/province [28] 0 0
Brest
Country [29] 0 0
France
State/province [29] 0 0
Bron
Country [30] 0 0
France
State/province [30] 0 0
Kremlin Bicetre
Country [31] 0 0
France
State/province [31] 0 0
Lille
Country [32] 0 0
France
State/province [32] 0 0
Marseille
Country [33] 0 0
Germany
State/province [33] 0 0
Berlin
Country [34] 0 0
Germany
State/province [34] 0 0
Bonn
Country [35] 0 0
Germany
State/province [35] 0 0
Frankfurt am Main
Country [36] 0 0
Germany
State/province [36] 0 0
München
Country [37] 0 0
Greece
State/province [37] 0 0
Athens
Country [38] 0 0
Hungary
State/province [38] 0 0
Budapest
Country [39] 0 0
Hungary
State/province [39] 0 0
Debrecen
Country [40] 0 0
Hungary
State/province [40] 0 0
Pécs
Country [41] 0 0
Ireland
State/province [41] 0 0
Dublin
Country [42] 0 0
Italy
State/province [42] 0 0
Campania
Country [43] 0 0
Italy
State/province [43] 0 0
Milano
Country [44] 0 0
Italy
State/province [44] 0 0
Vicenza
Country [45] 0 0
Japan
State/province [45] 0 0
Aichi
Country [46] 0 0
Japan
State/province [46] 0 0
Fukuoka
Country [47] 0 0
Japan
State/province [47] 0 0
Kanagawa
Country [48] 0 0
Japan
State/province [48] 0 0
Niigata
Country [49] 0 0
Japan
State/province [49] 0 0
Tokyo
Country [50] 0 0
Korea, Republic of
State/province [50] 0 0
Daegu-gwangyeoksi
Country [51] 0 0
Korea, Republic of
State/province [51] 0 0
Seoul-teukbyeolsi
Country [52] 0 0
Netherlands
State/province [52] 0 0
Amsterdam
Country [53] 0 0
Netherlands
State/province [53] 0 0
Utrecht
Country [54] 0 0
Spain
State/province [54] 0 0
Catalunya [Cataluña]
Country [55] 0 0
Spain
State/province [55] 0 0
Madrid, Comunidad De
Country [56] 0 0
Sweden
State/province [56] 0 0
Malmo
Country [57] 0 0
Switzerland
State/province [57] 0 0
Zürich
Country [58] 0 0
Taiwan
State/province [58] 0 0
Changhua County
Country [59] 0 0
Taiwan
State/province [59] 0 0
Taichung
Country [60] 0 0
Taiwan
State/province [60] 0 0
Taipei
Country [61] 0 0
Turkey
State/province [61] 0 0
Antalya
Country [62] 0 0
Turkey
State/province [62] 0 0
Istanbul
Country [63] 0 0
Turkey
State/province [63] 0 0
Izmir
Country [64] 0 0
United Kingdom
State/province [64] 0 0
London, City Of
Country [65] 0 0
United Kingdom
State/province [65] 0 0
Birmingham
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Hampshire

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?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04644575