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

Phase 1

Completed

Conditions: Coagulation Protein Disorders
Factor VIII (FVIII) Deficiency
Factor VIII (FVIII) Gene
Genetic Diseases, Inborn
Gene Transfer
Hemorrhagic Disorders
Gene Therapy
Factor VIII (FVIII)
Factor VIII (FVIII) Protein
Hematologic Diseases

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.

Recruitment & Eligibility

Inclusion Criteria

Be male and ≥18 years of age;
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;
Have had >150 exposure days (EDs) to any recombinant and/or plasma-derived FVIII concentrates or cryoprecipitates
Have no prior history of hypersensitivity or anaphylaxis associated with any FVIII or IV immunoglobulin administration
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)
Agree to use reliable barrier contraception after the administration of SPK-8016 until notified by the Investigator.

Exclusion Criteria

Have active hepatitis B or C
Have significant underlying liver disease.
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
Have detectable antibodies reactive with AAV-Spark capsid
Have history of chronic infection or other chronic disease
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
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;
Unable or unwilling to comply with the schedule of visits and study assessments described in the clinical protocol.

Arm && Interventions

Group	Intervention	Description
SPK-8016	SPK-8016	All participants who meet the eligibility criteria will receive an outpatient single intravenous (i.v.) administration of SPK-8016.

Primary Outcome Measures

Name	Time	Method
Annualized Infusion Rate	From 28 days post vector administration up to week 52
Number of Participants With Hepatic Transaminase Elevation Requiring Immunosuppression.	Up to week 52
Number of Participants With Adverse Events (AEs)	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.
Number of Bleeding Events (Spontaneous and Traumatic) Since 28 Day Post Vector Administration	From 28 days post vector administration up to week 52
Peak FVIII Activity Levels Assessed by Coagulation Clotting Assays	Up to week 52
Steady-state FVIII Activity Levels Assessed by Coagulation Clotting Assays	Up to week 52

Secondary Outcome Measures

Name	Time	Method
Time to Achieve Steady-state FVIII Activity Levels	Up to week 52
Number of Participants With Immune Responses to AAV Capsid Protein and BDD-hFVIII Transgene	Up to week 52
Number of Participants With Vector-shedding of SPK-8016 in Bodily Fluids	Up to week 52

Locations (11): Orthopaedic Institute for Children
🇺🇸
Los Angeles, California, United States
Weill Cornell Medicine
🇺🇸
New York, New York, United States
Illinois Bleeding and Clotting Disorders Institute
🇺🇸
Peoria, Illinois, United States
Mississippi Center for Advanced Medicine
🇺🇸
Madison, Mississippi, United States
Oregon Health & Science University
🇺🇸
Portland, Oregon, United States
Penn State Health
🇺🇸
Hershey, Pennsylvania, United States
Jefferson University Hospitals
🇺🇸
Philadelphia, Pennsylvania, United States
Hemophilia Center of Western Pennsylvania
🇺🇸
Pittsburgh, Pennsylvania, United States
Virginia Commonwealth University School of Medicine
🇺🇸
Richmond, Virginia, United States
Children's Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
University of Michigan
🇺🇸
Ann Arbor, Michigan, United States