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

• ClinicalTrials.gov Identifier: NCT03734588
• Recruitment Status: Active, not recruiting
• First Posted: November 8, 2018
• Last Update Posted: November 2, 2020
• Sponsor: Spark Therapeutics
• Information provided by (Responsible Party): Spark Therapeutics

Tracking Information

• First Submitted Date: November 6, 2018
• First Posted Date: November 8, 2018
• Last Update Posted Date: November 2, 2020
• Actual Study Start Date: January 30, 2019
• Estimated Primary Completion Date: November 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Dose-finding Study of SPK-8016 Gene Therapy in Patients With Hemophilia A to Support Evaluation in Individuals With FVIII Inhibitors
• Official Title: 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: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• 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

Genetic: SPK-8016

adeno-associated viral vector

Study Arms

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

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: November 7, 2018): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 2021
• Estimated Primary Completion Date: November 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Genetically male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03734588
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Responsible Party: Spark Therapeutics
• Study Sponsor: Spark Therapeutics
• Collaborators: Not Provided

Investigators

• Principal Investigator: Lindsey George, MD; Children's Hospital of Philadelphia

• PRS Account: Spark Therapeutics
• Verification Date: October 2020