NIPH Clinical Trials Search

JAPANESE
国立保健医療科学院
JRCT ID: jRCT2080225103

Registered date:02/03/2020

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

Basic Information

Recruitment status completed
Health condition(s) or Problem(s) studiedFactor VIII deficiency
Date of first enrollment13/05/2020
Target sample size150
Countries of recruitmentArgentina,Australia,Belgium,Brazil,Bulgaria,Canada,France,Germany,Greece,Hungary,Italy,Republic of Korea,Mexico,Netherlands,Spain,Taiwan,United Kingdom,United States,Japan
Study typeInterventional
Intervention(s)Investigational drug: efanesoctocog alfa (BIVV001) Control drug: NA Dosage and Administration: - Prophylaxis arm: prophylaxis treatment regimen with once weekly injection of BIVV001 for 52 weeks - On-demand then prophylaxis arm: on-demand regimen with BIVV001 for 26 weeks followed by prophylaxis treatment regimen with once weekly injection of BIVV001 for 26 weeks

Outcome(s)

Primary Outcome1. Annualized bleeding rate (ABR) in prophylaxis treatment arm [Time frame: baseline to 52 weeks] ABR will be estimated for the weekly (QW) prophylaxis treatment arm.
Secondary Outcome1. Intra-patient comparison of ABR of participants of this study to the ABR of same participants previously participated 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. 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. 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. 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 then prophylaxis arm 6. Percentage of participants who maintain FVIII activity levels [Time frame: 52 weeks] 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: 52 weeks] 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: 52 weeks] 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. 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 (e.g., swelling and strength) assessed by the HJHS in prophylaxis treatment arm. 13. Annualized Joint Bleeding Rate (AJBR) [Time frame: baseline to week 52] AJBR per study arm and treatment regimen 14. Target joint resolution [Time frame: baseline to week 52] Target joint resolution at week 52, based on ISTH criteria, for the prophylaxis treatment arm 15. Changes in Haem-A-QoL total score and physical health score [Time frame for evaluation: 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 16. Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Pain intensity [Time frame: baseline to week 52] Changes in PROMIS Pain Intensity from Baseline to Week 52 in prophylaxis treatment arm 17. 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 18. 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 19. Number of injections and dose to maintain hemostasis during perioperative period for major surgery [Time frame: baseline to week 52] 20. Total BIVV001 consumption during perioperative period for major surgery [Time frame: baseline to week 52] 21. Number of blood component transfusions used during perioperative period for major surgery [Time frame: baseline to week 52] 22. Type of blood component transfusions used during perioperative period for major surgery [Time frame: baseline to week 52] 23. Estimated blood loss during perioperative period for major surgery [Time frame: baseline to week 52] 24. Number of participants with occurrences of adverse events (AEs) and serious adverse events (SAEs) [Time frame: baseline to week 52] Participants with occurrences of AEs and SAEs 25. 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 26. Number of participants with occurrence of embolic and thrombotic events [Time frame: baseline to week 52] 27. PK parameter: Maximum activity (Cmax) [Time frame: baseline to week 52] 28. PK parameter: Elimination half-life (t1/2) [Time frame: baseline to week 26] 29. PK parameter: Total clearance (CL) [Time frame: baseline to week 26] 30. PK parameter: Total clearance at steady state (CLss) [Time frame: baseline to week 26] 31. PK parameter: Accumulation index (AI) [Time frame: baseline to week 26] 32. PK parameter: Area under the activity time curve (AUC) [Time frame: baseline to week 26] 33. PK parameter: Volume of distribution at steady state (Vss) [Time frame: baseline to week 26] 34. PK parameter: Mean residence time (MRT) [Time frame: baseline to week 26] 35. PK parameter: Incremental recovery (IR) [Time frame: baseline to week 26] 36. PK parameter: Trough activity (Ctrough) [Time frame: baseline to week 52] 37. PK parameter: Time above FVIII activity levels [Time frame: baseline to week 52]

Key inclusion & exclusion criteria

Age minimum>= 12age old
Age maximumNot applicable
GenderBoth
Include criteria1. 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 exposure days. 4. 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. 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.
Exclude criteriaParticipants are excluded from the study if any of the following criteria apply: - 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.

Related Information

Contact

Public contact
Name Unit Study Clinical
Address Tokyo Opera City Tower, 3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo 163-1488, Japan
Telephone +81-3-6301-3670
E-mail clinical-trials-jp@sanofi.com
Affiliation Sanofi K.K.
Scientific contact
Name Tomoyuki Tanaka
Address Tokyo Opera City Tower, 3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo 163-1488, Japan
Telephone +81-3-6301-3670
E-mail clinical-trials-jp@sanofi.com
Affiliation Sanofi K.K.