A Gene Transfer Study for Hemophilia A

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Sequential Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 5, 2023

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.

Interventions

  • Genetic: SPK-8011
    • A novel, bio-engineered, recombinant adeno-associated viral vector carrying human factor VIII gene

Arms, Groups and Cohorts

  • Experimental: SPK-8011
    • All participants who meet the eligibility criteria will receive an outpatient single intravenous (i.v.) administration of SPK-8011.

Clinical Trial Outcome Measures

Primary Measures

  • Number of study-related adverse events, including clinically significant abnormal laboratory values
    • Time Frame: 52 weeks
    • adverse events
  • Changes from baseline in FVIII activity levels after a single outpatient administration of SPK-8011
    • Time Frame: 52 weeks
    • changes in FVIII activity levels

Secondary Measures

  • Kinetic assessment of SPK-8011 including shedding of vector DNA in bodily fluids
    • Time Frame: 52 weeks
    • vector shedding
  • Number of participants requiring a course of steroid therapy for the elevations in liver enzymes
    • Time Frame: 52 weeks
    • number of participants requiring steroids

Participating in This Clinical Trial

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 Eligibility: Male

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Spark Therapeutics, Inc.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Clinical Trial Director, Study Director, Spark Therapeutics, Inc.

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