Brief Title
A Gene Transfer Study for Hemophilia A
Official Title
Gene-transfer, Open-label, Dose-escalation Study of SPK-8011 [Adeno-associated Viral Vector With B-domain Deleted Human Factor VIII Gene] in Individuals With Hemophilia A
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 treatment is intravenous (i.v.) injections of factor VIII protein products, either 2-3 times weekly or in response to bleeding. Recent preliminary clinical data of a hemophilia B gene transfer study (which is also being conducted by Spark Therapeutics) shows all study participants achieving therapeutic factor IX activity levels (average of maintaining factor IX activity levels around 30% of normal with no confirmed bleeds, after receiving Spark gene transfer, with the approach of using the novel bio-engineered recombinant adeno-associated viral (rAAV) vector carrying a high specific activity of a factor IX gene. The approach being tested in this clinical research study uses a further modified novel AAV vector (with a stronger attraction to the human liver) to deliver the human factor VIII (hFVIII) gene into liver cells so that they can produce factor VIII protein.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Number of study-related adverse events, including clinically significant abnormal laboratory values
Secondary Outcome
Kinetic assessment of SPK-8011 including shedding of vector DNA in bodily fluids
Condition
Hemophilia A
Intervention
SPK-8011
Study Arms / Comparison Groups
SPK-8011
Description: All participants who meet the eligibility criteria will receive an outpatient single intravenous (i.v.) administration of SPK-8011.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Genetic
Estimated Enrollment
50
Start Date
January 26, 2017
Completion Date
December 2023
Primary Completion Date
December 2023
Eligibility Criteria
Inclusion Criteria: - Males age18 years or older - Confirmed diagnosis of hemophilia A as evidenced by their medical history with plasma FVIII activity levels ≤ 2% of normal - Have received >150 exposure days (EDs) to FVIII concentrates or cryoprecipitate - Have experienced >10 bleeding events over the previous 12 months only if receiving on-demand therapy and having FVIII baseline level 1-2% of normal - Have no prior history of allergic reaction to any FVIII product - Have no measurable inhibitor against Factor VIII as assessed by the central laboratory and have no prior history of inhibitors to FVIII protein - Agree to use reliable barrier contraception Exclusion Criteria: - 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 (* 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
Gender
Male
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Clinical Trial Director, ,
Location Countries
Australia
Location Countries
Australia
Administrative Informations
NCT ID
NCT03003533
Organization ID
SPK-8011-101
Responsible Party
Sponsor
Study Sponsor
Spark Therapeutics
Study Sponsor
Clinical Trial Director, Study Director, Spark Therapeutics, Inc.
Verification Date
March 2023