A Phase 3, Open-label Interventional Study of an Intravenous Recombinant Coagulation Factor VIII Fc-von Willebrand Factor-XTEN Fusion Protein, BIVV001, in Patients With Severe Hemophilia A (XTEND-1)

• Register: EUCTR
• Last refreshed on: 26 October 2021
• Main ID: EUCTR2019-002023-15-NL
• Date of registration: 25/11/2019
• Prospective Registration: Yes
• Primary sponsor: Bioverativ Therapeutics Inc. (a Sanofi company)
• Public title: A Phase 3, Open-label Interventional Study of an Intravenous Recombinant Coagulation Factor VIII Fc-von Willebrand Factor-XTEN Fusion Protein, BIVV001, in Patients With Severe Hemophilia A (XTEND-1)
• Scientific title: 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 - XTEND-1
• Target sample size: 164
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-002023-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: Cross over: Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Colombia, France, Germany, Greece, Hungary, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Spain, Taiwan, United Kingdom, United States

Contacts

• Name: Project Management
• Affiliation: PSI CRO AG

• Name: Project Management
• Affiliation: PSI CRO AG

Key inclusion & exclusion criteria

Inclusion criteria:
1. Participant, male or female, must be equal to or greater than 12 years of age inclusive, at the time of signing the informed consent.
2. 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
3. Previous treatment for hemophilia A (prophylaxis or on demand) with any recombinant and/or plasma-derived FVIII, or cryoprecipitate for at least 150 EDs.
4. Current regimen includes one of the following:
• Prophylactic treatment regimen with a marketed 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 marketed 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 is accepting to move to a prophylaxis treatment regimen after 26-week on-demand period.
5. Willingness and ability of the participant or surrogate (a caregiver or a family member =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.
6. 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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 10
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 149
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

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 BU/mL at Screening. History of a positive inhibitor test defined as =0.6 BU/mL. Family history of inhibitors will not exclude the participant.
- Use of Emicizumab within the 20 weeks prior to Screening
- Major surgery within 8 weeks prior to Screening.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

severe hemophilia A
MedDRA version: 20.0 Level: PT Classification code 10016080 Term: Factor VIII deficiency System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Intervention(s)

Product Name: Recombinant coagulation FVIII Fc – von Willebrand factor – XTEN fusion protein
Product Code: BIVV001 (rFVIIIFc-VWF-XTEN)
Pharmaceutical Form: Powder for injection
INN or Proposed INN: Efanesoctocog alfa
CAS Number: 2252477-42-0
Current Sponsor code: BIVV001 (rFVIIIFc-VWF-XTEN)
Other descriptive name: RECOMBINANT HUMAN COAGULATION FACTOR VIII FC - VON WILLEBRAND FACTOR - XTEN FUSION PROTEIN
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 250-

Product Name: Recombinant coagulation FVIII Fc – von Willebrand factor – XTEN fusion protein
Product Code: BIVV001 (rFVIIIFc-VWF-XTEN)
Pharmaceutical Form: Powder for injection
INN or Proposed INN: Efanesoctocog alfa
CAS Number: 2252477-42-0
Current Sponsor code: BIVV001 (rFVIIIFc-VWF-XTEN)
Other descriptive name: RECOMBINANT HUMAN COAGULATION FACTOR VIII FC - VON WILLEBRAND FACTOR - XTEN FUSION PROTEIN
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 500-

Product Name: Recombinant coagulation FVIII Fc – von Willebrand factor – XTEN fusion protein
Product Code: BIVV001 (rFVIIIFc-VWF-XTEN)
Pharmaceutical Form: Powder for injection
INN or Proposed INN: Efanesoctocog alfa
CAS Number: 2252477-42-0
Current Sponsor code: BIVV001 (rFVIIIFc-VWF-XTEN)
Other descriptive name: RECOMBINANT HUMAN COAGULATION FACTOR VIII FC - VON WILLEBRAND FACTOR - XTEN FUSION PROTEIN
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 1000-

Product Name: Recombinant coagulation FVIII Fc – von Willebrand factor – XTEN fusion protein
Product Code: BIVV001 (rFVIIIFc-VWF-XTEN)
Pharmaceutical Form: Powder for injection
INN or Proposed INN: Efanesoctocog alfa
CAS Number: 2252477-42-0
Current Sponsor code: BIVV001 (rFVIIIF

Primary Outcome(s)

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 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 (QoL) outcomes
- To evaluate the efficacy of BIVV001 for perioperative management
Safety Objective
- To evaluate the safety and tolerability of BIVV001 treatment
Pharmacokinetic Objective
- To assess the PK of BIVV001 based on the one stage activated partial thromboplastin time (aPTT) and two-stage chromogenic FVIII activity assays
Exploratory Objectives
- To evaluate joint-health structural outcomes via ultrasound using the JADE protocol and/or HEAD-US
- To assess the impact of BIVV001 treatment on patient reported outcome (PRO) measurements and physical activity (measures per study arm and treatment regimen)

Main Objective: To evaluate the efficacy of BIVV001 as a prophylaxis treatment

Primary end point(s): Primary Efficacy Endpoint:
Annualized bleeding rate (ABR) in prophylaxis treatment arm

Timepoint(s) of evaluation of this end point: baseline to 52 weeks

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: For efficacy, safety and PK assessments, planned time points are according to the Schedule of Activities in the study protocol

Secondary end point(s): Secondary Efficacy Endpoints:
-Intra-patient comparison of ABR of participants of this study to the ABR of same participants previously treated in an observational study
-Annualized bleeding rate (ABR) by type of bleed
-Annualized bleeding rate (ABR) by location of bleed
-Annualized bleeding rate (ABR) for all bleeding episodes including untreated bleeding episodes
-Intra-patient comparison of ABR during the weekly once (QW) prophylaxis treatment period versus ABR during the on-demand treatment period
- Percentage of participants who maintain FVIII activity levels
-Number of injection and dose of BIVV001 to treat a bleeding episode
-Percentage of bleeding episodes treated with a single injection of BIVV001
-Assessment of response to BIVV001 treatment of individual bleeding episodes
-Physician’s global assessment of the participant’s response based on BIVV001 treatment
-Total annualized BIVV001 consumption
-Annualized Joint Bleeding Rate (AJBR)
-Target joint resolution
-Change in Hemophilia Joint Health Score (HJHS) total score and domain scores
-Change in PROMIS-SF Physical Function
-Changes in Haem-A-QoL total score and physical health score
-Investigators’ or Surgeons’ assessment of participant’s hemostatic response to BIVV001 treatment
-Number of injections and dose to maintain hemostasis during perioperative period for major surgery
-Total BIVV001 consumption during perioperative period for major surgery
-Number of blood component transfusions used during perioperative period for major surgery
-Type of blood component transfusions used during perioperative period for major surgery
-Estimated blood loss during perioperative period for major surgery
-Number of participants with occurance of adverse events (AEs) and serious adverse events (SAEs)
-Number of participants with inhibitor development
-Number of participants with occurrence of embolic and thrombotic events
-PK parameter: Maximum activity (Cmax)
-PK parameter: Elimination half-life (t1/2)
-PK parameter: Total clearance (CL)
-PK parameter: Total clearance at steady state (CLss)
-PK parameter: Accumulation index (AI)
-PK parameter: Area under the activity time curve (AUC)
-PK parameter: Volume of distribution at steady state (Vss)
-PK parameter: Mean residence time (MRT)
-PK parameter: Incremental recovery (IR)
-PK parameter: Trough activity (Ctrough)
-PK parameter: Time above FVIII activity levels

Secondary ID(s)

17464

EFC16293

2019-002023-15-DE

NCT04161495

Source(s) of Monetary Support

Bioverativ Therapeutics Inc. (a Sanofi company)

Ethics review

Status: Approved
Approval date:
Contact: