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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)

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ClinicalTrials.gov Identifier: NCT04161495
Recruitment Status : Recruiting
First Posted : November 13, 2019
Last Update Posted : July 30, 2020
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Bioverativ, a Sanofi company )

Brief Summary:

Primary Objective:

- To evaluate the efficacy of BIVV001 as a prophylaxis treatment in prophylaxis treatment arm.

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 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
  • To evaluate the safety and tolerability of BIVV001 treatment
  • To assess the pharmacokinetics (PK) of BIVV001 based on the 1-stage activated partial thromboplastin time (aPTT) and 2-stage chromogenic FVIII activity assays

Condition or disease Intervention/treatment Phase
Factor VIII Deficiency Drug: BIVV001 Phase 3

Detailed Description:

Participants in prophylaxis arm will receive a weekly prophylactic dose of BIVV001 for 52 weeks. Participants in on-demand arm will receive BIVV001 on demand for 26 weeks followed by a switch to weekly prophylaxis for another 26 weeks.

The Sponsor plans to perform a long-term safety trial. Enrollment in this open-label extension study will be offered to patients completing the treatment period based on eligibility criteria.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A 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
Actual Study Start Date : December 4, 2019
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hemophilia

Arm Intervention/treatment
Experimental: Prophylaxis
Participants will receive BIVV001 once-weekly (QW) during a prophylaxis treatment regimen for 52 weeks
Drug: BIVV001
Pharmaceutical form:solution for injection Route of administration: intravenous injection

Experimental: On Demand
Participants will receive BIVV001 on demand for 26 weeks, followed by a switch to a prophylaxis treatment regimen with BIVV001 for 26 weeks.
Drug: BIVV001
Pharmaceutical form:solution for injection Route of administration: intravenous injection




Primary Outcome Measures :
  1. Annualized bleeding rate (ABR) in prophylaxis treatment arm [ Time Frame: baseline to 52 weeks ]
    Annualized bleeding rate (ABR) will be estimated for the weekly (QW) prophylaxis treatment arm.


Secondary Outcome Measures :
  1. Intra-patient comparison of ABR of participants of this study to the ABR of same participants previously treated in an observational study [ Time Frame: baseline to week 52 ]
    Intra patient comparison of ABR during the BIVV001 weekly prophylaxis treatment period versus the historical prophylaxis ABR for participants in prophylaxis treatment who participated in Study 242HA201/OBS16221, an observational study

  2. Annualized bleeding rate (ABR) by type of bleed [ Time Frame: baseline to week 52 ]
    ABR by type of bleed such as spontaneous or traumatic per study arm

  3. Annualized bleeding rate (ABR) by location of bleed [ Time Frame: baseline to week 52 ]
    ABR by location of bleed such as joint, muscle, internal, or skin/mucosa per study arm

  4. Annualized bleeding rate (ABR) for all bleeding episodes including untreated bleeding episodes [ Time Frame: baseline to week 52 ]
    ABR for all bleeding episodes (including untreated bleeding episodes) for prophylaxis treatment per study arm

  5. Intra-patient comparison of ABR during the weekly once (QW) prophylaxis treatment period versus ABR during the on-demand treatment period [ Time Frame: baseline to week 52 ]
    Intra-patient comparison of ABR during the QW prophylaxis treatment period versus the ABR during the on-demand treatment period in the on-demand Arm

  6. Percentage of participants who maintain FVIII activity levels [ Time Frame: week 52 ]
    Percentage of participants who maintain FVIII activity levels in prophylaxis treatment arm

  7. Number of injection and dose of BIVV001 to treat a bleeding episode [ Time Frame: week 52 ]
    Number of injections and dose of BIVV001 to treat a bleeding episode per study arm and treatment regimen

  8. Percentage of bleeding episodes treated with a single injection of BIVV001 [ Time Frame: week 52 ]
    Percentage of bleeding episodes treated with a single injection of BIVV001 per study arm and treatment regimen

  9. Assessment of response to BIVV001 treatment of individual bleeding episodes [ Time Frame: baseline to week 52 ]
    Assessment of response to BIVV001 treatment of individual bleeding episodes based on the International Society on Thrombosis and Haemostasis (ISTH) 4-point response scale per study arm and treatment regimen

  10. Physician's global assessment of the participant's response based on BIVV001 treatment [ Time Frame: baseline to week 52 ]
    Physician's global assessment (PGA) of participant's response to BIVV001 treatment based on a 4-point response scale per study arm and treatment regimen

  11. Total annualized BIVV001 consumption [ Time Frame: baseline to week 52 ]
    Total annualized BIVV001 consumption per participant per study arm and treatment regimen

  12. Annualized Joint Bleeding Rate (AJBR) [ Time Frame: baseline to week 52 ]
    Annualized Joint Bleeding Rate (AJBR) per study arm and treatment regimen

  13. Target joint resolution [ Time Frame: At week 52 ]
    Target joint resolution at week 52, based on ISTH criteria, for the prophylaxis treatment arm

  14. Change in Hemophilia Joint Health Score (HJHS) total score and domain scores [ Time Frame: baseline to week 52 ]
    Change from baseline to week 52 in total score and domain scores (eg, swelling and strength) assessed by the HJHS in prophylaxis treatment arm.

  15. Change in Patient-Reported Outcomes Measurement Information System-Short Form (PROMIS-SF) Physical Function [ Time Frame: baseline to week 52 ]
    Changes in PROMIS-SF Physical Function (>=18 years old) measures from baseline to week 52 in prophylaxis treatment arm

  16. Changes in Haem-A-QoL total score and physical health score [ Time Frame: baseline to week 52 ]
    Changes in Haem-A-QoL (≥ 17 years old) total score and physical health score measures from baseline to Week 52 in prophylaxis treatment arm

  17. Investigators' or Surgeons' assessment of participant's hemostatic response to BIVV001 treatment [ Time Frame: baseline to week 52 ]
    Investigators' or Surgeons' assessment of participant's hemostatic response to BIVV001 treatment on the ISTH 4 point response for surgical procedures scale

  18. Number of injections and dose to maintain hemostasis during perioperative period for major surgery [ Time Frame: baseline to week 52 ]
  19. Total BIVV001 consumption during perioperative period for major surgery [ Time Frame: baseline to week 52 ]
  20. Number of blood component transfusions used during perioperative period for major surgery [ Time Frame: baseline to week 52 ]
  21. Type of blood component transfusions used during perioperative period for major surgery [ Time Frame: baseline to week 52 ]
  22. Estimated blood loss during perioperative period for major surgery [ Time Frame: baseline to week 52 ]
  23. Number of participants with occurrences of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: baseline to week 52 ]
    Participants with occurrences of adverse events (AEs) and serious adverse events (SAEs)

  24. Number of participants with inhibitor development [ Time Frame: baseline to week 52 ]
    Development of inhibitors (neutralizing antibodies directed against VIII [FVIII] as determined via the Nijmegen modified Bethesda assay

  25. Number of participants with occurrence of embolic and thrombotic events [ Time Frame: baseline to week 52 ]
  26. PK parameter: Maximum activity (Cmax) [ Time Frame: baseline to week 52 ]
  27. PK parameter: Elimination half-life (t1/2) [ Time Frame: baseline to week 26 ]
  28. PK parameter: Total clearance (CL) [ Time Frame: baseline to week 26 ]
  29. PK parameter: Total clearance at steady state (CLss) [ Time Frame: baseline to week 26 ]
  30. PK parameter: Accumulation index (AI) [ Time Frame: baseline to week 26 ]
  31. PK parameter: Area under the activity time curve (AUC) [ Time Frame: baseline to week 26 ]
  32. PK parameter: Volume of distribution at steady state (Vss) [ Time Frame: baseline to week 26 ]
  33. PK parameter: Mean residence time (MRT) [ Time Frame: baseline to week 26 ]
  34. PK parameter: Incremental recovery (IR) [ Time Frame: baseline to week 26 ]
  35. PK parameter: Trough activity (Ctrough) [ Time Frame: baseline to week 52 ]
  36. PK parameter: Time above FVIII activity levels [ Time Frame: baseline to week 26 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria :

  • Participant, male or female, must be equal to or greater than 12 years of age inclusive, at the time of signing the informed consent.
  • 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.
  • Current regimen includes one of the following:

    • Prophylactic treatment regimen with a 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 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.
  • 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.
  • 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.

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.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04161495


Contacts
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Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext option 6 Contact-US@sanofi.com

Locations
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United States, California
Investigational Site Number 920 Recruiting
Los Angeles, California, United States, 90007-2664
United States, Nevada
Investigational Site Number 906 Recruiting
Las Vegas, Nevada, United States, 89113
United States, Washington
Investigational Site Number 902 Recruiting
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Bioverativ, a Sanofi company
Investigators
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Study Director: Clinical Sciences & Operations Sanofi
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Responsible Party: Bioverativ, a Sanofi company
ClinicalTrials.gov Identifier: NCT04161495    
Other Study ID Numbers: EFC16293
2019-002023-15 ( EudraCT Number )
U1111-1223-4867 ( Other Identifier: UTN )
First Posted: November 13, 2019    Key Record Dates
Last Update Posted: July 30, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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://www.clinicalstudydatarequest.com/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn