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

NCT03734588 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: SPK-8016-101
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 11

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.

Conditions

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

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (3)

• 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

Study Arms (1)

SPK-8016

EXPERIMENTAL

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

Genetic: SPK-8016

Interventions

SPK-8016 GENETIC

adeno-associated viral vector

SPK-8016

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Genetically male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be male and ≥18 years of age;
• Have clinically severe hemophilia A, defined as:
• \<1% (\<1 IU/dL) endogenous FVIII activity levels as historically documented by a certified laboratory or screening data results; OR
• % (1-2 IU/dL) endogenous FVIII activity levels and \> 10 bleeding events per year (in the last 52 weeks prior to screening); OR
• % (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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Spark Therapeutics, Inc.: lead

Study Sites (11)

Orthopaedic Institute for Children

Los Angeles, California, 90007, United States

Location

Illinois Bleeding and Clotting Disorders Institute

Peoria, Illinois, 61615, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Mississippi Center for Advanced Medicine

Madison, Mississippi, 39110, United States

Location

Weill Cornell Medicine

New York, New York, 10065, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Penn State Health

Hershey, Pennsylvania, 17033, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Jefferson University Hospitals

Philadelphia, Pennsylvania, 19107, United States

Location

Hemophilia Center of Western Pennsylvania

Pittsburgh, Pennsylvania, 15213, United States

Location

Virginia Commonwealth University School of Medicine

Richmond, Virginia, 23219, United States

Location

MeSH Terms

Conditions

Blood Coagulation Disorders; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemophilia A; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Hematologic Diseases; Hemorrhagic Disorders

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Tiffany Chang, MD, MAS Clinical Development Lead, Hematology
• Organization: Spark Therapeutics

Tiffany.chang@sparktx.com

Please Email

Study Officials

• Tiffany Chang, MD

  Spark Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2018
• First Posted: November 8, 2018
• Study Start: January 30, 2019
• Primary Completion: October 14, 2020
• Study Completion: January 19, 2023
• Last Updated: February 23, 2024
• Results First Posted: February 23, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)