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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

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ClinicalTrials.gov Identifier: NCT03734588
Recruitment Status : Recruiting
First Posted : November 8, 2018
Last Update Posted : March 13, 2019
Sponsor:
Information provided by (Responsible Party):
Spark Therapeutics

Tracking Information
First Submitted Date  ICMJE November 6, 2018
First Posted Date  ICMJE November 8, 2018
Last Update Posted Date March 13, 2019
Actual Study Start Date  ICMJE January 30, 2019
Estimated Primary Completion Date April 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 7, 2018)
  • Number of study-related adverse events, including clinically significant abnormal laboratory values. [ Time Frame: 52 weeks ]
    Adverse events.
  • Occurrence of hepatic transaminase elevation requiring immunosuppression. [ Time Frame: 52 weeks ]
    Number of incidences of hepatic transaminase elevation where immunosuppression is required.
  • Number of bleeding events (spontaneous and traumatic) after vector administration. [ Time Frame: 52 weeks ]
    Bleeding events.
  • Number of FVIII infusions after vector administration. [ Time Frame: 52 weeks ]
    FVIII infusions.
  • Peak and steady-state FVIII activity levels. [ Time Frame: 52 weeks ]
    Peak and steady-state FVIII activity levels assessed by coagulation clotting assays.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03734588 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 7, 2018)
  • Vector shedding of SPK-8016 in bodily fluids. [ Time Frame: 52 weeks ]
    Vector shedding.
  • Incidence of immune response to AAV capsid protein and transgene product. [ Time Frame: 52 weeks ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose-finding Study of SPK-8016 Gene Therapy in Patients With Hemophilia A to Support Evaluation in Individuals With FVIII Inhibitors
Official Title  ICMJE Dose-finding Study of SPK-8016 Gene Therapy in Patients With Hemophilia A to Support Evaluation in Individuals With FVIII Inhibitors
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE Genetic: SPK-8016
adeno-associated viral vector
Study Arms  ICMJE Experimental: SPK-8016
All participants who meet the eligibility criteria will receive an outpatient single intravenous (i.v.) administration of SPK-8016.
Intervention: Genetic: SPK-8016
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 7, 2018)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2020
Estimated Primary Completion Date April 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Gender Based Eligibility: Yes
Gender Eligibility Description: Genetically male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Clinical Director 215-220-9300 clinicaltrials@sparktx.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03734588
Other Study ID Numbers  ICMJE SPK-8016-101
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Spark Therapeutics
Study Sponsor  ICMJE Spark Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Lindsey George, MD Children's Hospital of Philadelphia
PRS Account Spark Therapeutics
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP