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: February 22, 2023
• Sponsor: Spark Therapeutics
• Information provided by (Responsible Party): Spark Therapeutics

Study Description

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

Study Design

• 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
• Estimated Primary Completion Date: March 2023
• Estimated Study Completion Date: December 2023

Arms and Interventions

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

Outcome Measures

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 ]

Eligibility Criteria

• 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

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.

Contacts and Locations

Locations

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

Investigators

• Study Director: Tiffany Chang, MD; Spark Therapeutics

More Information

• Responsible Party: Spark Therapeutics
• ClinicalTrials.gov Identifier: NCT03734588
• Other Study ID Numbers: SPK-8016-101
• First Posted: November 8, 2018
• Last Update Posted: February 22, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

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