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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. Read our disclaimer for details. Identifier: NCT03734588
Recruitment Status : Completed
First Posted : November 8, 2018
Results First Posted : February 23, 2024
Last Update Posted : February 23, 2024
Information provided by (Responsible Party):
Spark Therapeutics, Inc.

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 to evaluate the safety, efficacy, and tolerability of SPK-8016 in adult males with severe hemophilia A and no measurable inhibitor against FVIII.

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)
Actual Enrollment : 4 participants
Allocation: N/A
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
Actual Primary Completion Date : October 14, 2020
Actual Study Completion Date : January 19, 2023

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 Participants With Adverse Events (AEs) [ Time Frame: Up to week 52 ]
    An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

  2. Number of Participants With Hepatic Transaminase Elevation Requiring Immunosuppression. [ Time Frame: Up to week 52 ]
  3. Peak FVIII Activity Levels Assessed by Coagulation Clotting Assays [ Time Frame: Up to week 52 ]
  4. Steady-state FVIII Activity Levels Assessed by Coagulation Clotting Assays [ Time Frame: Up to week 52 ]
  5. Number of Bleeding Events (Spontaneous and Traumatic) Since 28 Day Post Vector Administration [ Time Frame: From 28 days post vector administration up to week 52 ]
  6. Annualized Infusion Rate [ Time Frame: From 28 days post vector administration up to week 52 ]

Secondary Outcome Measures :
  1. Time to Achieve Steady-state FVIII Activity Levels [ Time Frame: Up to week 52 ]
  2. Number of Participants With Vector-shedding of SPK-8016 in Bodily Fluids [ Time Frame: Up to week 52 ]
  3. Number of Participants With Immune Responses to AAV Capsid Protein and BDD-hFVIII Transgene [ Time Frame: Up to week 52 ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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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:

  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:

  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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United States, California
Orthopaedic Institute for Children
Los Angeles, California, United States, 90007
United States, Illinois
Illinois Bleeding and Clotting Disorders Institute
Peoria, Illinois, United States, 61615
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Mississippi
Mississippi Center for Advanced Medicine
Madison, Mississippi, United States, 39110
United States, New York
Weill Cornell Medicine
New York, New York, United States, 10065
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Penn State Health
Hershey, Pennsylvania, United States, 17033
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Jefferson University Hospitals
Philadelphia, Pennsylvania, United States, 19107
Hemophilia Center of Western Pennsylvania
Pittsburgh, Pennsylvania, United States, 15213
United States, Virginia
Virginia Commonwealth University School of Medicine
Richmond, Virginia, United States, 23219
Sponsors and Collaborators
Spark Therapeutics, Inc.
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Study Director: Tiffany Chang, MD Spark Therapeutics, Inc.
  Study Documents (Full-Text)

Documents provided by Spark Therapeutics, Inc.:
Study Protocol  [PDF] March 19, 2021
Statistical Analysis Plan  [PDF] March 19, 2021

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Responsible Party: Spark Therapeutics, Inc. Identifier: NCT03734588    
Other Study ID Numbers: SPK-8016-101
First Posted: November 8, 2018    Key Record Dates
Results First Posted: February 23, 2024
Last Update Posted: February 23, 2024
Last Verified: February 2024
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
Hemophilia A
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