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Dose-finding Study of SPK-8016 Gene Therapy in Patients With Hemophilia A to Support Evaluation in Individuals With FVIII Inhibitors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03734588
Recruitment Status : Recruiting
First Posted : November 8, 2018
Last Update Posted : March 13, 2019
Information provided by (Responsible Party):
Spark Therapeutics

Brief Summary:
SPK-8016 is in development for the treatment of patients with inhibitors to FVIII. This Phase 1/2, open-label, non-randomized, dose-finding study is part one of a planned two part study of SPK-8016. Part one will evaluate the safety, efficacy, and tolerability of SPK-8016 in adult males with clinically severe hemophilia A and no measurable inhibitor against FVIII. Data obtained from Part 1 will inform the study design and dose selection for Part 2 in patients with FVIII inhibitors.

Condition or disease Intervention/treatment Phase
Adeno-Associated Virus (AAV) Blood Coagulation Disorder Blood Coagulation Disorders, Inherited Coagulation Protein Disorders Factor VIII (FVIII) Factor VIII (FVIII) Deficiency Factor VIII (FVIII) Gene Factor VIII (FVIII) Protein Genetic Diseases, Inborn Genetic Diseases, X-Linked Gene Therapy Gene Transfer Hematologic Diseases Hemorrhagic Disorders Recombinant Vector Inhibitors Genetic: SPK-8016 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Dose-finding Study of SPK-8016 Gene Therapy in Patients With Hemophilia A to Support Evaluation in Individuals With FVIII Inhibitors
Actual Study Start Date : January 30, 2019
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : April 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: SPK-8016
All participants who meet the eligibility criteria will receive an outpatient single intravenous (i.v.) administration of SPK-8016.
Genetic: SPK-8016
adeno-associated viral vector

Primary Outcome Measures :
  1. Number of study-related adverse events, including clinically significant abnormal laboratory values. [ Time Frame: 52 weeks ]
    Adverse events.

  2. Occurrence of hepatic transaminase elevation requiring immunosuppression. [ Time Frame: 52 weeks ]
    Number of incidences of hepatic transaminase elevation where immunosuppression is required.

  3. Number of bleeding events (spontaneous and traumatic) after vector administration. [ Time Frame: 52 weeks ]
    Bleeding events.

  4. Number of FVIII infusions after vector administration. [ Time Frame: 52 weeks ]
    FVIII infusions.

  5. Peak and steady-state FVIII activity levels. [ Time Frame: 52 weeks ]
    Peak and steady-state FVIII activity levels assessed by coagulation clotting assays.

Secondary Outcome Measures :
  1. Vector shedding of SPK-8016 in bodily fluids. [ Time Frame: 52 weeks ]
    Vector shedding.

  2. Incidence of immune response to AAV capsid protein and transgene product. [ Time Frame: 52 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Genetically male
Accepts Healthy Volunteers:   No

Inclusion Criteria for Part 1:

  1. Be male and ≥18 years of age;
  2. Have clinically severe hemophilia A, defined as:

    1. <1% (<1 IU/dL) endogenous FVIII activity levels as historically documented by a certified laboratory or screening data results; OR
    2. 1-2% (1-2 IU/dL) endogenous FVIII activity levels and > 10 bleeding events per year (in the last 52 weeks prior to screening); OR
    3. 1-2% (1-2 IU/dL) endogenous FVIII activity levels and on prophylaxis;
  3. Have had >150 exposure days (EDs) to any recombinant and/or plasma-derived FVIII concentrates or cryoprecipitates
  4. Have no prior history of hypersensitivity or anaphylaxis associated with any FVIII or IV immunoglobulin administration
  5. Have no measurable inhibitor against FVIII as assessed by central laboratory, have no confirmed history of clinically significant FVIII inhibitor, and no clinical signs or symptoms of decreased response to FVIII administration (Note: family history of inhibitors will not exclude study participation)
  6. Agree to use reliable barrier contraception after the administration of SPK-8016 until notified by the Investigator.

Exclusion Criteria for Part 1:

  1. Have active hepatitis B or C
  2. Have significant underlying liver disease.
  3. Have serological evidence of HIV-1 or HIV-2 with CD4 counts ≤200/mm3. Participants who are HIV-positive and stable, with an adequate CD4 count (>200/mm3) and undetectable viral load, and are on an antiretroviral drug regimen are eligible to enroll
  4. Have detectable antibodies reactive with AAV-Spark capsid
  5. Have history of chronic infection or other chronic disease
  6. Have been dosed in a previous gene therapy research trial within the last 52 weeks or with an investigational drug within the last 12 weeks
  7. Any concurrent clinically significant major disease (such as liver abnormalities or type I diabetes) or other condition that, in the opinion of the Investigator and/or Sponsor, makes the subject unsuitable for participation in the study;
  8. Unable or unwilling to comply with the schedule of visits and study assessments described in the clinical protocol.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03734588

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Contact: Clinical Director 215-220-9300

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United States, Mississippi
Mississippi Center for Advanced Medicine Recruiting
Madison, Mississippi, United States, 39110
Contact: Spencer K. Sullivan, MD   
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Lindsey George, MD   
Contact: Ben Samelson-Jones, MD   
United States, Virginia
Virginia Commonwealth University School of Medicine Recruiting
Richmond, Virginia, United States, 23219
Contact: J Christian Barrett, MD   
Sponsors and Collaborators
Spark Therapeutics
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Principal Investigator: Lindsey George, MD Children's Hospital of Philadelphia

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Responsible Party: Spark Therapeutics Identifier: NCT03734588     History of Changes
Other Study ID Numbers: SPK-8016-101
First Posted: November 8, 2018    Key Record Dates
Last Update Posted: March 13, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hemostatic Disorders
Hematologic Diseases
Blood Coagulation Disorders
Hemorrhagic Disorders
Coagulation Protein Disorders
Blood Coagulation Disorders, Inherited
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Vascular Diseases
Cardiovascular Diseases
Hemophilia A
Pathologic Processes
Factor VIII