Clinical trial NCT04644575: Long-term Safety and Efficacy of Efanesoctocog Alfa (BIVV001) in Previously Treated Patients With Hemophilia A
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Hemophilia A
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2020-11-25
Enrollment: 261
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: It is a 3-arm study with single intervention
Primary purpose: TREATMENT

Brief 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

Detailed 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.

Eligibility 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.

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.

Primary outcomes:
measure: Number of participants with the occurrence of inhibitor development (neutralizing antibodies detected against factor VIII [FVIII])
timeFrame: Baseline to month 48
Secondary outcomes:
measure: Annual bleeding rate (ABR)
timeFrame: Baseline to month 48
measure: Annualized bleeding rate (ABR) by type of bleed
timeFrame: Baseline to month 48
measure: Annualized bleeding rate (ABR) by location
timeFrame: Baseline to month 48
measure: Percentage of patients who maintain factor VIII (FVIII) above prespecified activity levels
timeFrame: Baseline to month 48
measure: Number of injections and dose of BIVV0001 to treat a bleeding episode
timeFrame: Month 48
measure: Percentage of bleeding episode treated with a single injection of BIVV001
timeFrame: Month 48
measure: Assessment of response to BIVV001 treatment of individual bleeding episodes
timeFrame: Baseline to month 48
measure: Physician's global assessment (PGA) of participants response to BIVV001
timeFrame: Baseline to month 48
measure: Total annualized BIVV001 consumption
timeFrame: Baseline to month 48
measure: Annualized joint bleeding rate (AJBR)
timeFrame: Baseline to month 48
measure: Target joint resolution
timeFrame: Month 48
measure: Change from baseline in Hemophilia Joint Health Score (HJHS)
timeFrame: Baseline to month 48
measure: Change from baseline in PROMIS-SF Physical Function
timeFrame: Baseline to month 48
measure: Change from baseline in Haem-A-QoL total score and physical health score
timeFrame: Baseline to month 48
measure: Change from baselin in Haemo-QoL total score and physical health score
timeFrame: Baseline to month 48
measure: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Baseline to month 48
measure: Number of participants with the occurrence of embolic and thrombotic events
timeFrame: Baseline to month 48
measure: PK parameter: Maximum activity (Cmax)
timeFrame: Baseline to week 52
measure: PK parameter: Elimination half-life (t1/2)
timeFrame: Baseline to week 26
measure: PK parameter: Total clearance (CL)
timeFrame: Baseline to week 26
measure: PK parameter: Total clearance at steady state (CLss)
timeFrame: Baseline to week 26
measure: PK parameter: Accumulation index (AI)
timeFrame: Baseline to week 26
measure: PK parameter: Area under the activity time curve (AUC)
timeFrame: Baseline to week 26
measure: PK parameter: Volume of distribution at steady state (Vss)
timeFrame: Baseline to week 26
measure: PK parameter: Mean residence time (MRT)
timeFrame: Baseline to week 26
measure: PK parameter: Incremental recovery (IR)
timeFrame: Baseline to week 52
measure: PK parameter: Trough activity (Ctrough)
timeFrame: Baseline to week 52
measure: PK parameter: Time above FVIII activity levels
timeFrame: Baseline to week 26
measure: Investigators' or Surgeons' assessment of participant's hemostatic response to BIVV001 treatment
timeFrame: Baseline to month 48
measure: Number of injections and dose to maintain hemostasis during perioperative period for major surgery
timeFrame: Baseline to month 48
measure: Total BIVV001 consumption during perioperative period for major surgery
timeFrame: Baseline to month 48
measure: Number and type of blood component transfusions used during perioperative period for major surgery
timeFrame: Baseline to month 48
measure: Estimated blood loss during perioperative period for major surgery
timeFrame: Baseline to month 48
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Orthopaedic Institute for Children Site Number : 8400003
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles Site Number : 8400009
state: California
city: San Diego
country: United States
facility: University of California San Diego Site Number : 8400007
state: California
city: Gainesville
country: United States
facility: University of Florida Health Site Number : 8400008
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta Site Number : 8400016
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center Site Number : 8400010
state: Illinois
city: Iowa City
country: United States
facility: Children's Hospital Of Iowa Site Number : 8400011
state: Iowa
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center Site Number : 8400006
state: Michigan
city: East Lansing
country: United States
facility: Michigan State University School Of Med Site Number : 8400002
state: Michigan
city: Las Vegas
country: United States
facility: Hemostasis and Thrombosis Center of Nevada Site Number : 8400001
state: Nevada
city: New York
country: United States
facility: New York Presbyterian Hospital/Weill Cornell Medical Center Site Number : 8400017
state: New York
city: Greenville
country: United States
facility: East Carolina University -2390 Hemby Ln Site Number : 8400015
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center Site Number : 8400012
state: Ohio
city: Columbus
country: United States
facility: Children's Research Institute Site Number : 8400013
state: Ohio
city: Seattle
country: United States
facility: Bloodworks Northwest Site Number : 8400005
state: Washington
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin Site Number : 8400014
state: Wisconsin
city: Caba
country: Argentina
facility: Investigational Site Number : 0320001
state: Ciudad De Buenos Aires
city: Godoy Cruz
country: Argentina
facility: Investigational Site Number : 0320002
state: Mendoza
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320003
city: Camperdown
country: Australia
facility: Investigational Site Number : 0360004
state: New South Wales
city: Westmead
country: Australia
facility: Investigational Site Number : 0360001
state: New South Wales
city: South Brisbane
country: Australia
facility: Investigational Site Number : 0360002
state: Queensland
city: Murdoch
country: Australia
facility: Investigational Site Number : 0360003
state: Western Australia
city: Sint-Lambrechts-Woluwe
country: Belgium
facility: Investigational Site Number : 0560003
city: Campinas
country: Brazil
facility: Hemocentro Campinas - UNICAMP Site Number : 0760001
state: São Paulo
city: Plovdiv
country: Bulgaria
facility: Investigational Site Number : 1000171
city: Sofia
country: Bulgaria
facility: Investigational Site Number : 1000172
city: Hamilton
country: Canada
facility: Investigational Site Number : 1240005
state: Ontario
city: Hamilton
country: Canada
facility: Investigational Site Number : 1240004
state: Ontario
city: Ottawa
country: Canada
facility: Investigational Site Number : 1240002
state: Ontario
city: Toronto
country: Canada
facility: Investigational Site Number : 1240001
state: Ontario
city: Beijing
country: China
facility: Investigational Site Number : 1560002
city: Beijing
country: China
facility: Investigational Site Number : 1560006
city: Guangzhou
country: China
facility: Investigational Site Number : 1560001
city: Hangzhou
country: China
facility: Investigational Site Number : 1560003
city: Hangzhou
country: China
facility: Investigational Site Number : 1560004
city: Jinan
country: China
facility: Investigational Site Number : 1560005
city: Kunming
country: China
facility: Investigational Site Number : 1560009
city: Kunming
country: China
facility: Investigational Site Number : 1560010
city: Lanzhou
country: China
facility: Investigational Site Number : 1560013
city: Suzhou
country: China
facility: Investigational Site Number : 1560007
city: Brest
country: France
facility: Investigational Site Number : 2500005
city: Bron
country: France
facility: Investigational Site Number : 2500004
city: Kremlin Bicetre
country: France
facility: Investigational Site Number : 2500001
city: Lille
country: France
facility: Investigational Site Number : 2500003
city: Marseille
country: France
facility: Investigational Site Number : 2500006
city: Berlin
country: Germany
facility: Investigational Site Number : 2760304
city: Bonn
country: Germany
facility: Investigational Site Number : 2760302
city: Frankfurt am Main
country: Germany
facility: Investigational Site Number : 2760001
city: München
country: Germany
facility: Investigational Site Number : 2760002
city: Athens
country: Greece
facility: Investigational Site Number : 3000001
city: Budapest
country: Hungary
facility: Investigational Site Number : 3480002
city: Debrecen
country: Hungary
facility: Investigational Site Number : 3480004
city: Pécs
country: Hungary
facility: Investigational Site Number : 3480005
city: Dublin
country: Ireland
facility: Investigational Site Number : 3720001
city: Napoli
country: Italy
facility: Investigational Site Number : 3800002
state: Campania
city: Milano
country: Italy
facility: Investigational Site Number : 3800001
city: Vicenza
country: Italy
facility: Investigational Site Number : 3800003
city: Nagoya-shi
country: Japan
facility: Investigational Site Number : 3920425
state: Aichi
city: Kitakyushu-shi
country: Japan
facility: Investigational Site Number : 3920423
state: Fukuoka
city: Kawasaki-shi
country: Japan
facility: Investigational Site Number : 3920426
state: Kanagawa
city: Kashihara-Shi
country: Japan
facility: Investigational Site Number : 3920422
state: Niigata
city: Shinjuku-ku
country: Japan
facility: Investigational Site Number : 3920421
state: Tokyo
city: Suginami-ku
country: Japan
facility: Investigational Site Number : 3920424
state: Tokyo
city: Daegu
country: Korea, Republic of
facility: Investigational Site Number : 4100603
state: Daegu-gwangyeoksi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100601
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100600
state: Seoul-teukbyeolsi
city: Amsterdam
country: Netherlands
facility: Investigational Site Number : 5280002
city: Utrecht
country: Netherlands
facility: Investigational Site Number : 5280001
city: Esplugues de Llobregat
country: Spain
facility: Investigational Site Number : 7240002
state: Catalunya [Cataluña]
city: Madrid
country: Spain
facility: Investigational Site Number : 7240001
state: Madrid, Comunidad De
city: Malmo
country: Sweden
facility: Investigational Site Number : 7520001
city: Zürich
country: Switzerland
facility: Investigational Site Number : 7560001
city: Changhua County
country: Taiwan
facility: Investigational Site Number : 1580005
city: Taichung
country: Taiwan
facility: Investigational Site Number : 1580001
city: Taichung
country: Taiwan
facility: Investigational Site Number : 1580003
city: Taipei
country: Taiwan
facility: Investigational Site Number : 1580002
city: Taipei
country: Taiwan
facility: Investigational Site Number : 1580004
city: Antalya
country: Turkey
facility: Investigational Site Number : 7920004
city: Istanbul
country: Turkey
facility: Investigational Site Number : 7920001
city: Izmir
country: Turkey
facility: Investigational Site Number : 7920003
city: London
country: United Kingdom
facility: Investigational Site Number : 8260005
state: London, City Of
city: London
country: United Kingdom
facility: Investigational Site Number : 8260001
state: London, City Of
city: Birmingham
country: United Kingdom
facility: Investigational Site Number : 8260003
city: Hampshire
country: United Kingdom
facility: Investigational Site Number : 8260004
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: