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

Hematologic Diseases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03734588
• Other study ID #: SPK-8016-101
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 30, 2019
• Est. completion date: January 19, 2023

Study information

• Verified date: February 2024
• Source: Spark Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 information / eligibility

• Status: Completed
• Enrollment: 4
• Est. completion date: January 19, 2023
• Est. primary completion date: October 14, 2020
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adeno-Associated Virus (AAV)
• Blood Coagulation Disorder
• Blood Coagulation Disorders
• Blood Coagulation Disorders, Inherited
• Coagulation Protein Disorders
• Factor VIII (FVIII)
• Factor VIII (FVIII) Deficiency
• Factor VIII (FVIII) Gene
• Factor VIII (FVIII) Protein
• Gene Therapy
• Gene Transfer
• Genetic Diseases, Inborn
• Genetic Diseases, X-Linked
• Hematologic Diseases
• Hemophilia A
• Hemorrhagic Disorders
• Hemostatic Disorders
• Inhibitors
• Recombinant
• Vector

Intervention

Genetic:
• SPK-8016
adeno-associated viral vector

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Spark Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Number of Participants With Hepatic Transaminase Elevation Requiring Immunosuppression.		Up to week 52
Primary	Peak FVIII Activity Levels Assessed by Coagulation Clotting Assays		Up to week 52
Primary	Steady-state FVIII Activity Levels Assessed by Coagulation Clotting Assays		Up to week 52
Primary	Number of Bleeding Events (Spontaneous and Traumatic) Since 28 Day Post Vector Administration		From 28 days post vector administration up to week 52
Primary	Annualized Infusion Rate		From 28 days post vector administration up to week 52
Secondary	Time to Achieve Steady-state FVIII Activity Levels		Up to week 52
Secondary	Number of Participants With Vector-shedding of SPK-8016 in Bodily Fluids		Up to week 52
Secondary	Number of Participants With Immune Responses to AAV Capsid Protein and BDD-hFVIII Transgene		Up to week 52