Hemophilia A MedDRA version: 20.0 Level: LLT Classification code 10060612 Term: Hemophilia A System Organ Class: 100000004850
Conditions
Interventions
Product Name: Recombinant coagulation FVIII Fc – von Willebrand factor – XTEN fusion
Product Code: BIVV001 (rFVIIIFc-VWF-XTEN)
Pharmaceutical Form: Powder for injection
INN or Proposed INN: Recombinan
Sponsors
Bioverativ Therapeutics Inc.
Eligibility
Sex/Gender
All
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 200 cells/mm³ and viral load of =65 years) yes F.1.3.1 Number of subjects for this age range 5
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the long-term safety of BIVV001 in previously treated subjects with hemophilia A;Secondary Objective: -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 ;Primary end point(s): Number of participants with the occurence of inhibitor development (neuatralizing antibodies detected against factor VIII [FVIII]) ;Timepoint(s) of evaluation of this end point: Baseline to month 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1/ Annual bleeding rate (ABR) 2/ Annualized bleeding rate (ABR) by type of bleed 3/ Annualized bleeding rate (ABR) by location 4 / Percentage of patients who maintain factor VIII (FVIII) above prespecified activity levels 5/ Number of injectons and dose of BIVV0001 to treat a bleeding episode 6/ Percentage of bleeding episode treated with a single injection of BIVV001 7/ Assessment of response to BIVV001 treatment of individual bleeding épisodes 8/ hysician's global assessment (PGA) of participants response to BIVV001 9/ Total annualized BIVV001 consumption 10/ Annulaized joint bleeding rate (AJBR) 11/ Target joint resolution 12/ Change from baseline in Hemophilia Joint Health Score (HJHS) 13/ Change from baseline in PROMIS-SF Physical Function 14/ Change from baseline in Haem-A-QoL total score and physical health score 15/ Change from baselin in Haemo-QoL total score and physical health score 16/ Number of participants with adverse events (AEs) and serious adverse events (SAEs) 17/ Number of particpants with the occurrence of embolic and thrombotic events 18/ PK parameter: Maximum activity (Cmax) 19/ PK parameter: Elimination half-life (t1/2) 20/ PK parameter: Total clearance (CL) 21/ PK parameter: Total clearance at steady state (CLss) 22/ PK parameter: Accumulation index (AI) 23/ PK parameter: Area under the activity time curve (AUC) 24/ PK parameter: Volume of distribution at steady state (Vss) 25/ PK parameter: Mean residence time (MRT) 26/ PK parameter: Incremental recovery (IR) 27/ PK parameter: Trough activity (Ctrough) 28/ PK parameter: Time above FVIII activity levels 29/ Investigators’ or Surgeons’ assessment of participant’s hemostatic response to BIVV001 treatment 30/ Number of injections and dose to maintain hemostasis during perioperative period for major surgery 31/ Total BIVV001 consumption during perioperative period for major surgery 32/ Number and type of blood component transfusions used during peri | — |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, China, Colombia, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Spain, Sweden, Switzerland, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactDirection des Opérations Cliniques
Sanofi-aventis France
Outcome results
None listed