A Gene Transfer Study for Hemophilia A

Hemophilia A Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03003533
• Other study ID #: SPK-8011-101
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 26, 2017
• Est. completion date: December 5, 2023

Study information

• Verified date: July 2023
• Source: Spark Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: December 5, 2023
• Est. primary completion date: December 5, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hemophilia A

Intervention

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

Locations

Country	Name	City	State
Australia	Royal Prince Alfred Hosptial	Camperdown	New South Wales
Australia	The Alfred Hospital	Melbourne
Canada	McMaster University Medical Centre and Juravinski Hospital	Hamilton	Ontario
Israel	Chaim Sheba Center	Ramat Gan	Tel Hashomer
Thailand	Mahidol University - Ramathibody Hospital	Bangkok
United States	Boston Children's Hospital	Boston	Massachusetts
United States	University of Florida Health	Gainesville	Florida
United States	Pennsylvania State University Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Mississippi Center for Advanced Medicine	Madison	Mississippi
United States	Weill Cornell Medicine-Comprehensive Center for Hemophilia and Coagulation Disorders	New York	New York
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Jefferson University Hospitals	Philadelphia	Pennsylvania
United States	Hemophilia Center of Western Pennsylvania	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	Virginia Commonwealth University School of Medicine	Richmond	Virginia
United States	University of California Davis - Hemostasis and Thrombosis Center	Sacramento	California

Sponsors (1)

Lead Sponsor	Collaborator
Spark Therapeutics

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Israel,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of study-related adverse events, including clinically significant abnormal laboratory values	adverse events	52 weeks
Primary	Changes from baseline in FVIII activity levels after a single outpatient administration of SPK-8011	changes in FVIII activity levels	52 weeks
Secondary	Kinetic assessment of SPK-8011 including shedding of vector DNA in bodily fluids	vector shedding	52 weeks
Secondary	Number of participants requiring a course of steroid therapy for the elevations in liver enzymes	number of participants requiring steroids	52 weeks