Long-term Safety and Efficacy of Efanesoctocog Alfa (BIVV001) in Previously Treated Patients With Hemophilia A
- Conditions
- Hemophilia A
- Interventions
- Drug: efanesoctocog alfa (BIVV001)
- Registration Number
- NCT04644575
- Lead Sponsor
- Bioverativ, a Sanofi company
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 261
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arm C: Newly initiated in BIVV001 with planned major surgery efanesoctocog alfa (BIVV001) This arm includes participants of any age who will be newly initiated on BIVV001 prophylaxis treatment once-weekly (QW) and will undergo planned major surgery after at least 6 initial EDs with BIVV001, and within 26 weeks from Day 1. After 52 weeks of treatment in arm C, participants will be able to roll into arm A. Arm A: Previously treated in BIVV001 study efanesoctocog alfa (BIVV001) This arm includes participants who have completed study EFC16293 or study EFC16295, participants who have completed Arm B or Arm C of this study (LTS16294) and roll over into Arm A, and participants who have completed any other potential BIVV001 study. Participants in this arm will continue receiving BIVV001 prophylaxis treatment once weekly (QW) for a total of 100 exposure days (EDs) cumulative from the parent study and this study. 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. Arm B: Newly initiated (China Only) in BIVV001 efanesoctocog alfa (BIVV001) This arm includes Chinese participants of any age who will be newly initiated on BIVV001 prophylaxis treatment once-weekly (QW) for 52 weeks. After 52 weeks of treatment in this arm B, participants will be able to roll over into arm A.
- Primary Outcome Measures
Name Time Method Number of participants with the occurrence of inhibitor development (neutralizing antibodies detected against factor VIII [FVIII]) Baseline to month 48 The number of participants with the occurrence of inhibitor development (neuatralizing antibodies detected against factor VIII \[FVIII\]) as determined via the Nijmegen modified Bethesda assay.
- Secondary Outcome Measures
Name Time Method Percentage of patients who maintain factor VIII (FVIII) above prespecified activity levels Baseline to month 48 Percentage of participants who maintain factor VIII (FVIII) activity levels over 7 days post dose during prophylaxis treatment per study arm and per parent study or arm.
Annual bleeding rate (ABR) Baseline to month 48 Annualized bleeding rate (ABR) for treated bleeding episodes and all bleeding episodes (including untreated bleeds).
Total annualized BIVV001 consumption Baseline to month 48 Total annualized BIVV001 consumption per participant during prophylaxis treatment
Target joint resolution Month 48 Target joint development, resolution and maintenance of target joint resolution based on ISTH criteria.
Physician's global assessment (PGA) of participants response to BIVV001 Baseline to month 48 Physician's global assessment (PGA) of participant's response to BIVV001 treatment based on a 4-point response scale .
Annualized bleeding rate (ABR) by type of bleed Baseline to month 48 Annualized bleeding rate (ABR) by type during prophylaxis treatment per study arm and parent study.
Annualized bleeding rate (ABR) by location Baseline to month 48 Annualized bleeding rate (ABR) by location during prophylaxis treatment per study arm and parent study.
Number of injections and dose of BIVV0001 to treat a bleeding episode Month 48 Percentage of bleeding episode treated with a single injection of BIVV001 Month 48 Assessment of response to BIVV001 treatment of individual bleeding episodes Baseline to month 48 Assessment of response to BIVV001 treatment of individual bleeding episodes based on the International Society on Thrombosis and Haemostasis (ISTH) 4-point response scale
PK parameter: Total clearance at steady state (CLss) Baseline to week 26 PK parameter: Accumulation index (AI) Baseline to week 26 PK parameter: Volume of distribution at steady state (Vss) Baseline to week 26 PK parameter: Mean residence time (MRT) Baseline to week 26 PK parameter: Incremental recovery (IR) Baseline to week 52 PK parameter: Trough activity (Ctrough) Baseline to week 52 Annualized joint bleeding rate (AJBR) Baseline to month 48 Change from baseline in Hemophilia Joint Health Score (HJHS) Baseline to month 48 Change from Baseline to the end of study visit in total score and domain scores (eg, swelling and strength) assessed by the Hemophilia Joint Health Score (HJHS)
Change from baseline in PROMIS-SF Physical Function Baseline to month 48 Change in Quality of Life (QoL) measures from baseline to end of study visit per study arm and per parent study arm: PROMIS-SF Physical Function (participants aged ≥18 years old).)
PK parameter: Time above FVIII activity levels Baseline to week 26 Investigators' or Surgeons' assessment of participant's hemostatic response to BIVV001 treatment Baseline to month 48 Investigators' or Surgeons' assessment of participant's hemostatic response to BIVV001 treatment on the ISTH 4 point response for surgical procedures scale.
Number of injections and dose to maintain hemostasis during perioperative period for major surgery Baseline to month 48 Change from baseline in Haem-A-QoL total score and physical health score Baseline to month 48 Change from baseline in Haemophilia QoL Questionnaire for Adults (Haem-A-QoL) total and physical health domain score on participants aged ≥17 years old.
Change from baselin in Haemo-QoL total score and physical health score Baseline to month 48 Change from baseline in Haemophilia QoL Questionnaire for Children (Haemo-QoL) total and physical health domain score on participants aged ≥4 to 16 years old and parent proxy for participants aged ≥4 to to \<12 years old.
Number of participants with adverse events (AEs) and serious adverse events (SAEs) Baseline to month 48 Participants with occurrences of treatment emergent adverse events (AEs) and serious adverse events (SAEs).
Number of participants with the occurrence of embolic and thrombotic events Baseline to month 48 Participants with the occurrence of embolic and thrombotic events.
PK parameter: Maximum activity (Cmax) Baseline to week 52 PK parameter: Elimination half-life (t1/2) Baseline to week 26 PK parameter: Total clearance (CL) Baseline to week 26 PK parameter: Area under the activity time curve (AUC) Baseline to week 26 Total BIVV001 consumption during perioperative period for major surgery Baseline to month 48 Number and type of blood component transfusions used during perioperative period for major surgery Baseline to month 48 Estimated blood loss during perioperative period for major surgery Baseline to month 48
Trial Locations
- Locations (85)
Investigational Site Number : 2500001
🇫🇷Kremlin Bicetre, France
Orthopaedic Institute for Children Site Number : 8400003
🇺🇸Los Angeles, California, United States
Children's Hospital Los Angeles Site Number : 8400009
🇺🇸Los Angeles, California, United States
East Carolina University -2390 Hemby Ln Site Number : 8400015
🇺🇸Greenville, North Carolina, United States
Investigational Site Number : 0360004
🇦🇺Camperdown, New South Wales, Australia
Investigational Site Number : 1240001
🇨🇦Toronto, Ontario, Canada
Hemostasis and Thrombosis Center of Nevada Site Number : 8400001
🇺🇸Las Vegas, Nevada, United States
Cincinnati Children's Hospital Medical Center Site Number : 8400012
🇺🇸Cincinnati, Ohio, United States
University of California San Diego Site Number : 8400007
🇺🇸San Diego, California, United States
Investigational Site Number : 0320003
🇦🇷Buenos Aires, Argentina
Investigational Site Number : 1000171
🇧🇬Plovdiv, Bulgaria
Investigational Site Number : 3920426
🇯🇵Kawasaki-shi, Kanagawa, Japan
Investigational Site Number : 3920421
🇯🇵Shinjuku-ku, Tokyo, Japan
Investigational Site Number : 0560003
🇧🇪Sint-Lambrechts-Woluwe, Belgium
Investigational Site Number : 1000172
🇧🇬Sofia, Bulgaria
Investigational Site Number : 3920422
🇯🇵Kashihara-Shi, Niigata, Japan
Hemocentro Campinas - UNICAMP Site Number : 0760001
🇧🇷Campinas, São Paulo, Brazil
Investigational Site Number : 3920424
🇯🇵Suginami-ku, Tokyo, Japan
Investigational Site Number : 5280002
🇳🇱Amsterdam, Netherlands
Investigational Site Number : 1580005
🇨🇳Changhua County, Taiwan
Investigational Site Number : 7560001
🇨🇭Zürich, Switzerland
Investigational Site Number : 1580001
🇨🇳Taichung, Taiwan
Investigational Site Number : 1580003
🇨🇳Taichung, Taiwan
Investigational Site Number : 1580002
🇨🇳Taipei, Taiwan
Investigational Site Number : 1560006
🇨🇳Beijing, China
Bloodworks Northwest Site Number : 8400005
🇺🇸Seattle, Washington, United States
University of Michigan Medical Center Site Number : 8400006
🇺🇸Ann Arbor, Michigan, United States
Rush University Medical Center Site Number : 8400010
🇺🇸Chicago, Illinois, United States
Michigan State University School Of Med Site Number : 8400002
🇺🇸East Lansing, Michigan, United States
Investigational Site Number : 0320001
🇦🇷Caba, Ciudad De Buenos Aires, Argentina
Investigational Site Number : 0360001
🇦🇺Westmead, New South Wales, Australia
Children's Research Institute Site Number : 8400013
🇺🇸Columbus, Ohio, United States
Investigational Site Number : 0360003
🇦🇺Murdoch, Western Australia, Australia
Investigational Site Number : 1240005
🇨🇦Hamilton, Ontario, Canada
Investigational Site Number : 1240004
🇨🇦Hamilton, Ontario, Canada
Investigational Site Number : 1560001
🇨🇳Guangzhou, China
Investigational Site Number : 1240002
🇨🇦Ottawa, Ontario, Canada
Investigational Site Number : 1560004
🇨🇳Hangzhou, China
Investigational Site Number : 7520001
🇸🇪Malmo, Sweden
Investigational Site Number : 7920004
🇹🇷Antalya, Turkey
Investigational Site Number : 8260003
🇬🇧Birmingham, United Kingdom
Investigational Site Number : 7240001
🇪🇸Madrid, Madrid, Comunidad De, Spain
Investigational Site Number : 1560002
🇨🇳Beijing, China
Investigational Site Number : 7240002
🇪🇸Esplugues de Llobregat, Catalunya [Cataluña], Spain
Investigational Site Number : 8260005
🇬🇧London, London, City Of, United Kingdom
Investigational Site Number : 8260001
🇬🇧London, London, City Of, United Kingdom
Investigational Site Number : 8260004
🇬🇧Hampshire, United Kingdom
Investigational Site Number : 4100600
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number : 7920001
🇹🇷Istanbul, Turkey
Investigational Site Number : 7920003
🇹🇷Izmir, Turkey
Investigational Site Number : 4100603
🇰🇷Daegu, Daegu-gwangyeoksi, Korea, Republic of
Investigational Site Number : 4100601
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number : 0360002
🇦🇺South Brisbane, Queensland, Australia
Children's Hospital of Wisconsin Site Number : 8400014
🇺🇸Milwaukee, Wisconsin, United States
Children's Healthcare of Atlanta Site Number : 8400016
🇺🇸Atlanta, Georgia, United States
University of Florida Health Site Number : 8400008
🇺🇸Gainesville, Florida, United States
Children's Hospital Of Iowa Site Number : 8400011
🇺🇸Iowa City, Iowa, United States
New York Presbyterian Hospital/Weill Cornell Medical Center Site Number : 8400017
🇺🇸New York, New York, United States
Investigational Site Number : 1560003
🇨🇳Hangzhou, China
Investigational Site Number : 1560005
🇨🇳Jinan, China
Investigational Site Number : 1560009
🇨🇳Kunming, China
Investigational Site Number : 1560010
🇨🇳Kunming, China
Investigational Site Number : 2500005
🇫🇷Brest, France
Investigational Site Number : 1560013
🇨🇳Lanzhou, China
Investigational Site Number : 2500004
🇫🇷Bron, France
Investigational Site Number : 1560007
🇨🇳Suzhou, China
Investigational Site Number : 2500003
🇫🇷Lille, France
Investigational Site Number : 2760302
🇩🇪Bonn, Germany
Investigational Site Number : 2500006
🇫🇷Marseille, France
Investigational Site Number : 2760304
🇩🇪Berlin, Germany
Investigational Site Number : 2760001
🇩🇪Frankfurt am Main, Germany
Investigational Site Number : 2760002
🇩🇪München, Germany
Investigational Site Number : 3000001
🇬🇷Athens, Greece
Investigational Site Number : 3480002
🇭🇺Budapest, Hungary
Investigational Site Number : 3480004
🇭🇺Debrecen, Hungary
Investigational Site Number : 3480005
🇭🇺Pécs, Hungary
Investigational Site Number : 3800002
🇮🇹Napoli, Campania, Italy
Investigational Site Number : 3800001
🇮🇹Milano, Italy
Investigational Site Number : 3800003
🇮🇹Vicenza, Italy
Investigational Site Number : 3720001
🇮🇪Dublin, Ireland
Investigational Site Number : 3920425
🇯🇵Nagoya-shi, Aichi, Japan
Investigational Site Number : 3920423
🇯🇵Kitakyushu-shi, Fukuoka, Japan
Investigational Site Number : 5280001
🇳🇱Utrecht, Netherlands
Investigational Site Number : 0320002
🇦🇷Godoy Cruz, Mendoza, Argentina
Investigational Site Number : 1580004
🇨🇳Taipei, Taiwan