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

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.

Study Overview

• Status: Completed
• Conditions: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Gene Therapy; Blood Coagulation Disorder; Gene Transfer; Adeno-Associated Virus (AAV); Factor VIII (FVIII); Factor VIII (FVIII) Deficiency; Factor VIII (FVIII) Gene; Factor VIII (FVIII) Protein; Recombinant; Vector; Inhibitors
• Intervention / Treatment: Genetic: SPK-8016

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90007
      • Orthopaedic Institute for Children
  • Illinois
    • Peoria, Illinois, United States, 61615
      • Illinois Bleeding and Clotting Disorders Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Mississippi
    • Madison, Mississippi, United States, 39110
      • Mississippi Center for Advanced Medicine
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medicine
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Health
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Philadelphia, Pennsylvania, United States, 19107
      • Jefferson University Hospitals
    • Pittsburgh, Pennsylvania, United States, 15213
      • Hemophilia Center of Western Pennsylvania
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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:

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs)	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.	Up to week 52
Number of Participants With Hepatic Transaminase Elevation Requiring Immunosuppression.		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
Number of Bleeding Events (Spontaneous and Traumatic) Since 28 Day Post Vector Administration		From 28 days post vector administration up to week 52
Annualized Infusion Rate		From 28 days post vector administration up to week 52

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Spark Therapeutics
• Investigators: Study Director: Tiffany Chang, MD, Spark Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2019
• Primary Completion (Actual): October 14, 2020
• Study Completion (Actual): January 19, 2023

Study Registration Dates

• First Submitted: November 6, 2018
• First Submitted That Met QC Criteria: November 7, 2018
• First Posted (Actual): November 8, 2018

Study Record Updates

• Last Update Posted (Estimated): February 23, 2024
• Last Update Submitted That Met QC Criteria: February 22, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hemostatic Disorders; Hemophilia A; Blood Coagulation Disorders; Hematologic Diseases; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Coagulation Protein Disorders; Blood Coagulation Disorders, Inherited
• Other Study ID Numbers: SPK-8016-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No