Long-term Safety and Efficacy of Efanesoctocog Alfa (BIVV001) in Previously Treated Patients With Hemophilia A

Hemophilia A Clinical Trial

— XTEND-ed  

Official 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04644575
• Other study ID #: LTS16294
• Secondary ID: U1111-1244-05172
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 23, 2021
• Est. completion date: January 15, 2027

Study information

• Verified date: June 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary Objective:

• To evaluate the long-term safety of BIVV001 in previously treated 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 safety and tolerability of BIVV001 treatment.

• To assess the PK of BIVV001 based on the one stage activated partial thromboplastin time (aPTT) and two-stage chromogenic FVIII activity assays (only applicable to Arm B).

• To evaluate the efficacy of BIVV001 for perioperative management

Description:

Participants will receive BIVV001 once weekly for a total of at least 100 exposure days to BIVV001 (including exposure during a BIVV001 parent study, if applicable). 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 261
• Est. completion date: January 15, 2027
• Est. primary completion date: January 15, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

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.

Related Conditions & MeSH terms

• Hemophilia A

Intervention

Drug:
• efanesoctocog alfa (BIVV001)
Pharmaceutical form:Solution for Injection Route of administration: Intravenous

Locations

Country	Name	City	State
Argentina	Investigational Site Number : 0320003	Buenos Aires
Argentina	Investigational Site Number : 0320001	Caba	Ciudad De Buenos Aires
Argentina	Investigational Site Number : 0320002	Godoy Cruz	Mendoza
Australia	Investigational Site Number : 0360004	Camperdown	New South Wales
Australia	Investigational Site Number : 0360003	Murdoch	Western Australia
Australia	Investigational Site Number : 0360002	South Brisbane	Queensland
Australia	Investigational Site Number : 0360001	Westmead	New South Wales
Belgium	Investigational Site Number : 0560003	Sint-Lambrechts-Woluwe
Brazil	Hemocentro Campinas - UNICAMP Site Number : 0760001	Campinas	São Paulo
Bulgaria	Investigational Site Number : 1000171	Plovdiv
Bulgaria	Investigational Site Number : 1000172	Sofia
Canada	Investigational Site Number : 1240004	Hamilton	Ontario
Canada	Investigational Site Number : 1240005	Hamilton	Ontario
Canada	Investigational Site Number : 1240002	Ottawa	Ontario
Canada	Investigational Site Number : 1240001	Toronto	Ontario
China	Investigational Site Number : 1560002	Beijing
China	Investigational Site Number : 1560006	Beijing
China	Investigational Site Number : 1560001	Guangzhou
China	Investigational Site Number : 1560003	Hangzhou
China	Investigational Site Number : 1560004	Hangzhou
China	Investigational Site Number : 1560005	Jinan
China	Investigational Site Number : 1560009	Kunming
China	Investigational Site Number : 1560010	Kunming
China	Investigational Site Number : 1560013	Lanzhou
China	Investigational Site Number : 1560007	Suzhou
France	Investigational Site Number : 2500005	Brest
France	Investigational Site Number : 2500004	Bron
France	Investigational Site Number : 2500001	Kremlin Bicetre
France	Investigational Site Number : 2500003	Lille
France	Investigational Site Number : 2500006	Marseille
Germany	Investigational Site Number : 2760304	Berlin
Germany	Investigational Site Number : 2760302	Bonn
Germany	Investigational Site Number : 2760001	Frankfurt am Main
Germany	Investigational Site Number : 2760002	München
Greece	Investigational Site Number : 3000001	Athens
Hungary	Investigational Site Number : 3480002	Budapest
Hungary	Investigational Site Number : 3480004	Debrecen
Hungary	Investigational Site Number : 3480005	Pécs
Ireland	Investigational Site Number : 3720001	Dublin
Italy	Investigational Site Number : 3800001	Milano
Italy	Investigational Site Number : 3800002	Napoli	Campania
Italy	Investigational Site Number : 3800003	Vicenza
Japan	Investigational Site Number : 3920422	Kashihara-Shi	Niigata
Japan	Investigational Site Number : 3920426	Kawasaki-shi	Kanagawa
Japan	Investigational Site Number : 3920423	Kitakyushu-shi	Fukuoka
Japan	Investigational Site Number : 3920425	Nagoya-shi	Aichi
Japan	Investigational Site Number : 3920421	Shinjuku-ku	Tokyo
Japan	Investigational Site Number : 3920424	Suginami-ku	Tokyo
Korea, Republic of	Investigational Site Number : 4100603	Daegu	Daegu-gwangyeoksi
Korea, Republic of	Investigational Site Number : 4100600	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number : 4100601	Seoul	Seoul-teukbyeolsi
Netherlands	Investigational Site Number : 5280002	Amsterdam
Netherlands	Investigational Site Number : 5280001	Utrecht
Spain	Investigational Site Number : 7240002	Esplugues de Llobregat	Catalunya [Cataluña]
Spain	Investigational Site Number : 7240001	Madrid	Madrid, Comunidad De
Sweden	Investigational Site Number : 7520001	Malmo
Switzerland	Investigational Site Number : 7560001	Zürich
Taiwan	Investigational Site Number : 1580005	Changhua County
Taiwan	Investigational Site Number : 1580001	Taichung
Taiwan	Investigational Site Number : 1580003	Taichung
Taiwan	Investigational Site Number : 1580002	Taipei
Taiwan	Investigational Site Number : 1580004	Taipei
Turkey	Investigational Site Number : 7920004	Antalya
Turkey	Investigational Site Number : 7920001	Istanbul
Turkey	Investigational Site Number : 7920003	Izmir
United Kingdom	Investigational Site Number : 8260003	Birmingham
United Kingdom	Investigational Site Number : 8260004	Hampshire
United Kingdom	Investigational Site Number : 8260001	London	London, City Of
United Kingdom	Investigational Site Number : 8260005	London	London, City Of
United States	University of Michigan Medical Center Site Number : 8400006	Ann Arbor	Michigan
United States	Children's Healthcare of Atlanta Site Number : 8400016	Atlanta	Georgia
United States	Rush University Medical Center Site Number : 8400010	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center Site Number : 8400012	Cincinnati	Ohio
United States	Children's Research Institute Site Number : 8400013	Columbus	Ohio
United States	Michigan State University School Of Med Site Number : 8400002	East Lansing	Michigan
United States	University of Florida Health Site Number : 8400008	Gainesville	Florida
United States	East Carolina University -2390 Hemby Ln Site Number : 8400015	Greenville	North Carolina
United States	Children's Hospital Of Iowa Site Number : 8400011	Iowa City	Iowa
United States	Hemostasis and Thrombosis Center of Nevada Site Number : 8400001	Las Vegas	Nevada
United States	Children's Hospital Los Angeles Site Number : 8400009	Los Angeles	California
United States	Orthopaedic Institute for Children Site Number : 8400003	Los Angeles	California
United States	Children's Hospital of Wisconsin Site Number : 8400014	Milwaukee	Wisconsin
United States	New York Presbyterian Hospital/Weill Cornell Medical Center Site Number : 8400017	New York	New York
United States	University of California San Diego Site Number : 8400007	San Diego	California
United States	Bloodworks Northwest Site Number : 8400005	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Bioverativ, a Sanofi company

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Bulgaria,  Canada,  China,  France,  Germany,  Greece,  Hungary,  Ireland,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Spain,  Sweden,  Switzerland,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with the occurrence of inhibitor development (neutralizing antibodies detected against factor VIII [FVIII])	The number of participants with the occurrence of inhibitor development (neuatralizing antibodies detected against factor VIII [FVIII]) as determined via the Nijmegen modified Bethesda assay.	Baseline to month 48
Secondary	Annual bleeding rate (ABR)	Annualized bleeding rate (ABR) for treated bleeding episodes and all bleeding episodes (including untreated bleeds).	Baseline to month 48
Secondary	Annualized bleeding rate (ABR) by type of bleed	Annualized bleeding rate (ABR) by type during prophylaxis treatment per study arm and parent study.	Baseline to month 48
Secondary	Annualized bleeding rate (ABR) by location	Annualized bleeding rate (ABR) by location during prophylaxis treatment per study arm and parent study.	Baseline to month 48
Secondary	Percentage of patients who maintain factor VIII (FVIII) above prespecified activity levels	Percentage of participants who maintain factor VIII (FVIII) activity levels over 7 days post dose during prophylaxis treatment per study arm and per parent study or arm.	Baseline to month 48
Secondary	Number of injections and dose of BIVV0001 to treat a bleeding episode		Month 48
Secondary	Percentage of bleeding episode treated with a single injection of BIVV001		Month 48
Secondary	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	Baseline to month 48
Secondary	Physician's global assessment (PGA) of participants response to BIVV001	Physician's global assessment (PGA) of participant's response to BIVV001 treatment based on a 4-point response scale .	Baseline to month 48
Secondary	Total annualized BIVV001 consumption	Total annualized BIVV001 consumption per participant during prophylaxis treatment	Baseline to month 48
Secondary	Annualized joint bleeding rate (AJBR)		Baseline to month 48
Secondary	Target joint resolution	Target joint development, resolution and maintenance of target joint resolution based on ISTH criteria.	Month 48
Secondary	Change from baseline in Hemophilia Joint Health Score (HJHS)	Change from Baseline to the end of study visit in total score and domain scores (eg, swelling and strength) assessed by the Hemophilia Joint Health Score (HJHS)	Baseline to month 48
Secondary	Change from baseline in PROMIS-SF Physical Function	Change in Quality of Life (QoL) measures from baseline to end of study visit per study arm and per parent study arm: PROMIS-SF Physical Function (participants aged =18 years old).)	Baseline to month 48
Secondary	Change from baseline in Haem-A-QoL total score and physical health score	Change from baseline in Haemophilia QoL Questionnaire for Adults (Haem-A-QoL) total and physical health domain score on participants aged =17 years old.	Baseline to month 48
Secondary	Change from baselin in Haemo-QoL total score and physical health score	Change from baseline in Haemophilia QoL Questionnaire for Children (Haemo-QoL) total and physical health domain score on participants aged =4 to 16 years old and parent proxy for participants aged =4 to to <12 years old.	Baseline to month 48
Secondary	Number of participants with adverse events (AEs) and serious adverse events (SAEs)	Participants with occurrences of treatment emergent adverse events (AEs) and serious adverse events (SAEs).	Baseline to month 48
Secondary	Number of participants with the occurrence of embolic and thrombotic events	Participants with the occurrence of embolic and thrombotic events.	Baseline to month 48
Secondary	PK parameter: Maximum activity (Cmax)		Baseline to week 52
Secondary	PK parameter: Elimination half-life (t1/2)		Baseline to week 26
Secondary	PK parameter: Total clearance (CL)		Baseline to week 26
Secondary	PK parameter: Total clearance at steady state (CLss)		Baseline to week 26
Secondary	PK parameter: Accumulation index (AI)		Baseline to week 26
Secondary	PK parameter: Area under the activity time curve (AUC)		Baseline to week 26
Secondary	PK parameter: Volume of distribution at steady state (Vss)		Baseline to week 26
Secondary	PK parameter: Mean residence time (MRT)		Baseline to week 26
Secondary	PK parameter: Incremental recovery (IR)		Baseline to week 52
Secondary	PK parameter: Trough activity (Ctrough)		Baseline to week 52
Secondary	PK parameter: Time above FVIII activity levels		Baseline to week 26
Secondary	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.	Baseline to month 48
Secondary	Number of injections and dose to maintain hemostasis during perioperative period for major surgery		Baseline to month 48
Secondary	Total BIVV001 consumption during perioperative period for major surgery		Baseline to month 48
Secondary	Number and type of blood component transfusions used during perioperative period for major surgery		Baseline to month 48
Secondary	Estimated blood loss during perioperative period for major surgery		Baseline to month 48