A Gene Transfer Study for Hemophilia A

January 8, 2024 updated by: Spark Therapeutics

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

25

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Melbourne, Australia, 3004
        • The Alfred Hospital
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Royal Prince Alfred Hosptial
  • Canada
    • Ontario
      • Hamilton, Ontario, Canada, L8N 3Z5
        • McMaster University Medical Centre and Juravinski Hospital
  • Israel
    • Tel Hashomer
      • Ramat Gan, Tel Hashomer, Israel, 526000
        • Chaim Sheba Center
  • Thailand
      • Bangkok, Thailand, 10400
        • Mahidol University - Ramathibody Hospital
  • United States
    • California
      • Sacramento, California, United States, 94817
        • University of California Davis - Hemostasis and Thrombosis Center
    • Florida
      • Gainesville, Florida, United States, 32610
        • University of Florida Health
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Boston Children's Hospital
    • Mississippi
      • Madison, Mississippi, United States, 39110
        • Mississippi Center for Advanced Medicine
    • New York
      • New York, New York, United States, 10065
        • Weill Cornell Medicine-Comprehensive Center for Hemophilia and Coagulation Disorders
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 10733
        • Pennsylvania State University Milton S. Hershey Medical Center
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
      • Philadelphia, Pennsylvania, United States, 19107
        • Jefferson University Hospitals
      • Pittsburgh, Pennsylvania, United States, 15213
        • Hemophilia Center of Western Pennsylvania
    • Virginia
      • Richmond, Virginia, United States, 23219
        • Virginia Commonwealth University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: SPK-8011
All participants who meet the eligibility criteria will receive an outpatient single intravenous (i.v.) administration of SPK-8011.
Genetic: SPK-8011
A novel, bio-engineered, recombinant adeno-associated viral vector carrying human factor VIII gene

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Spark Therapeutics

Investigators

  • Study Director: Clinical Trial Director, Spark Therapeutics, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 26, 2017

Primary Completion (Actual)

December 5, 2023

Study Completion (Actual)

December 5, 2023

Study Registration Dates

First Submitted

December 16, 2016

First Submitted That Met QC Criteria

December 21, 2016

First Posted (Estimated)

December 28, 2016

Study Record Updates

Last Update Posted (Actual)

January 9, 2024

Last Update Submitted That Met QC Criteria

January 8, 2024

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SPK-8011-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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