A Gene Transfer Study for Hemophilia A
- Conditions
- Hemophilia A
- Interventions
- Genetic: SPK-8011
- Registration Number
- NCT03003533
- Lead Sponsor
- Spark Therapeutics, Inc.
- Brief Summary
This clinical research study is being conducted by Spark Therapeutics, Inc. to determine the safety and efficacy of the factor VIII gene transfer treatment with SPK-8011 in individuals with hemophilia A.
- Detailed Description
Hemophilia A is a condition in which blood is unable to clot effectively. It is caused by a mutation or deletion in the gene that is responsible for producing blood-clotting factor VIII protein. Individuals with hemophilia A suffer from repeated bleeding episodes, often into the joints, which can cause chronic joint disease and sometime results in death due to the inability of the blood to clot efficiently. This chronic joint disease can have significant physical, psychosocial, and quality-of-life effects, including financial burden. The current standard of care includes the use of factor-based therapies which are given either as prophylaxis or to treat bleeding, as well as new non-factor prophylaxis therapies.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 25
- Males age 18 years or older
- Confirmed diagnosis of hemophilia A as evidenced by their medical history with baseline FVIII activity levels <=2%
- Have received >150 exposure days (EDs) to FVIII concentrates or cryoprecipitate
- Have no prior history of allergic reaction to any FVIII product
- Have no measurable inhibitor against FVIII as assessed by the central laboratory and have no prior history of inhibitors to FVIII protein and no clinical signs or symptoms of decreased response to FVIII administration
- Agree to use reliable barrier contraception
- Evidence of active hepatitis B or C
- Currently on antiviral therapy for hepatitis B or C
- Have significant underlying liver disease
- Have serological evidence* of HIV-1 or HIV-2 with CD4 counts ≤200/mm3 and who are on an antiretroviral drug regimen (* participants who are HIV+ and stable with CD4 count >200/mm3 and undetectable viral load are eligible to enroll)
- Have detectable antibodies reactive with AAV-Spark200 capsid
- Participated in a gene transfer trial within the last 52 weeks or in a clinical trial with an investigational product within the last 12 weeks
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description SPK-8011 SPK-8011 All participants who meet the eligibility criteria will receive an outpatient single intravenous (i.v.) administration of SPK-8011.
- Primary Outcome Measures
Name Time Method Number of Participants With Treatment-emergent Adverse Events (TEAEs) From date of first dose to Week 52/End of Study (EOS) Visit An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse events (SAEs) were defined as adverse events that result in death, are life-threatening, require inpatient hospitalization or prolongation of existing hospitalization, result in persistent or significant disability or incapacity, are a congenital anomaly or birth defect, or are an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A TEAE is defined as an AE with an onset date on or following SPK-8011 administration. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Number of Participants Who Received Corticosteroids for Presumed Immune Response Up to Week 52/EOS Visit Peak Factor VIII (FVIII) Activity Levels Assessed by One-Stage Coagulation Assay (OSA) Up to Week 52/EOS visit Median peak FVIII activity up to Week 52
Nominal FVIII Level by OSA at Week 52/EOS Up to Week 52/EOS Visit Steady-state FVIII activity measured by median FVIII levels at week 52 by OSA.
Spontaneous Bleeds Annualized Bleeding Rate Week 5 up to Week 52/EOS Visit Total Annualized FVIII Infusion Rate Week 5 up to Week 52/EOS Visit
- Secondary Outcome Measures
Name Time Method Time to Achieve Peak FVIII Activity Level Up to Week 52/EOS Visit Number of Participants With Vector-shedding Confirmed Below Quantifiable Limits (BQL) of SPK-8011-101 in Bodily Fluids Up to Week 52/EOS Visit Incidence of Immune Response to the BDD-hFVIII Transgene Up to Week 52/EOS Visit
Trial Locations
- Locations (16)
Jefferson University Hospitals
🇺🇸Philadelphia, Pennsylvania, United States
University of California Davis - Hemostasis and Thrombosis Center
🇺🇸Sacramento, California, United States
Chaim Sheba Center
🇮🇱Ramat Gan, Tel Hashomer, Israel
Pennsylvania State University Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
The Alfred Hospital
🇦🇺Melbourne, Australia
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Royal Prince Alfred Hosptial
🇦🇺Camperdown, New South Wales, Australia
Hemophilia Center of Western Pennsylvania
🇺🇸Pittsburgh, Pennsylvania, United States
Virginia Commonwealth University School of Medicine
🇺🇸Richmond, Virginia, United States
Mahidol University - Ramathibody Hospital
🇹🇭Bangkok, Thailand
McMaster University Medical Centre and Juravinski Hospital
🇨🇦Hamilton, Ontario, Canada
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
University of Florida Health
🇺🇸Gainesville, Florida, United States
Weill Cornell Medicine-Comprehensive Center for Hemophilia and Coagulation Disorders
🇺🇸New York, New York, United States
Mississippi Center for Advanced Medicine
🇺🇸Madison, Mississippi, United States