Phase 2 N=4 Treatment

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

Adeno-Associated Virus (AAV) · Blood Coagulation Disorder · Blood Coagulation Disorders, Inherited · Coagulation Protein Disorders · Factor VIII (FVIII)

Bottom Line

View on ClinicalTrials.gov: NCT03734588 ↗

Enrolled (actual)

Serious AEs

50.0%

Results posted

Feb 2024

Primary outcome: Primary: Number of Participants With Adverse Events (AEs) — 4 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: SPK-8016 (Genetic)
Age: Adult, Older Adult · 18+ yrs
Sex: Male
Sponsor: Spark Therapeutics, Inc.
Primary completion: Oct 2020

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants With Adverse Events (AEs)	4	—
PRIMARY Number of Participants With Hepatic Transaminase Elevation Requiring Immunosuppression.	—	—
PRIMARY Peak FVIII Activity Levels Assessed by Coagulation Clotting Assays	NA	—
PRIMARY Steady-state FVIII Activity Levels Assessed by Coagulation Clotting Assays	NA	—
PRIMARY Number of Bleeding Events (Spontaneous and Traumatic) Since 28 Day Post Vector Administration	6; 1	—
PRIMARY Annualized Infusion Rate	NA	—
SECONDARY Time to Achieve Steady-state FVIII Activity Levels	NA	—
SECONDARY Number of Participants With Vector-shedding of SPK-8016 in Bodily Fluids	—	—
SECONDARY Number of Participants With Immune Responses to AAV Capsid Protein and BDD-hFVIII Transgene	3	—

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.

Eligibility Criteria

Inclusion Criteria

Be male and ≥18 years of age;
Have clinically severe hemophilia A, defined as:
10 bleeding events per year (in the last 52 weeks prior to screening); OR
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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03734588). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.