A Gene Transfer Study for Hemophilia A

NCT03003533 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: SPK-8011-101
• Study Type: interventional
• Target: 25
• Locations: 5 countries
• Sites: 16

Brief Summary

This clinical research study is being conducted by Spark Therapeutics, Inc. to determine the safety and efficacy of the factor VIII gene transfer treatment with SPK-8011 in individuals with hemophilia A.

Conditions

Hemophilia A

Keywords

Adeno-Associated Virus (AAV); 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; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Gene Therapy; Gene Transfer; Hematologic Diseases; Hemorrhagic Disorders; Recombinant; Vector

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse events (SAEs) were defined as adverse events that result in death, are life-threatening, require inpatient hospitalization or prolongation of existing hospitalization, result in persistent or significant disability or incapacity, are a congenital anomaly or birth defect, or are an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A TEAE is defined as an AE with an onset date on or following SPK-8011 administration. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

  From date of first dose to Week 52/End of Study (EOS) Visit

• Number of Participants Who Received Corticosteroids for Presumed Immune Response

  Up to Week 52/EOS Visit

• Peak Factor VIII (FVIII) Activity Levels Assessed by One-Stage Coagulation Assay (OSA)

  Median peak FVIII activity up to Week 52

  Up to Week 52/EOS visit

• Nominal FVIII Level by OSA at Week 52/EOS

  Steady-state FVIII activity measured by median FVIII levels at week 52 by OSA.

  Up to Week 52/EOS Visit

• Spontaneous Bleeds Annualized Bleeding Rate

  Week 5 up to Week 52/EOS Visit

• Total Annualized FVIII Infusion Rate

  Week 5 up to Week 52/EOS Visit

Secondary Outcomes (3)

• Time to Achieve Peak FVIII Activity Level

  Up to Week 52/EOS Visit

• Number of Participants With Vector-shedding Confirmed Below Quantifiable Limits (BQL) of SPK-8011-101 in Bodily Fluids

  Up to Week 52/EOS Visit

• Incidence of Immune Response to the BDD-hFVIII Transgene

  Up to Week 52/EOS Visit

Study Arms (4)

SPK-8011 5x10^11 vg/kg

EXPERIMENTAL

Participants received a single intravenous (IV) infusion of SPK-8011 5x10\^11 vector genomes per kilogram (vg/kg) body weight.

Genetic: SPK-8011

SPK-8011 1x10^12 vg/kg

EXPERIMENTAL

Participants received a single IV infusion of SPK-8011 1x10\^12 vg/kg.

Genetic: SPK-8011

SPK-8011 2x10^12 vg/kg

EXPERIMENTAL

Participants received a single IV infusion of SPK-8011 2x10\^12 vg/kg.

Genetic: SPK-8011

SPK-8011 1.5x10^12 vg/kg

EXPERIMENTAL

Participants received a single IV infusion of SPK-8011 1.5x10\^12 vg/kg.

Genetic: SPK-8011

Interventions

SPK-8011 GENETIC

A novel, bio-engineered, recombinant adeno-associated viral vector carrying human factor VIII gene

SPK-8011 1.5x10^12 vg/kg; SPK-8011 1x10^12 vg/kg; SPK-8011 2x10^12 vg/kg; SPK-8011 5x10^11 vg/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males age 18 years or older
• Confirmed diagnosis of hemophilia A as evidenced by their medical history with baseline FVIII activity levels \<=2%
• Have received \>150 exposure days (EDs) to FVIII concentrates or cryoprecipitate
• Have no prior history of allergic reaction to any FVIII product
• Have no measurable inhibitor against FVIII as assessed by the central laboratory and have no prior history of inhibitors to FVIII protein and no clinical signs or symptoms of decreased response to FVIII administration
• Agree to use reliable barrier contraception

You may not qualify if:

• Evidence of active hepatitis B or C
• Currently on antiviral therapy for hepatitis B or C
• Have significant underlying liver disease
• Have serological evidence\* of HIV-1 or HIV-2 with CD4 counts ≤200/mm3 and who are on an antiretroviral drug regimen (\* participants who are HIV+ and stable with CD4 count \>200/mm3 and undetectable viral load are eligible to enroll)
• Have detectable antibodies reactive with AAV-Spark200 capsid
• Participated in a gene transfer trial within the last 52 weeks or in a clinical trial with an investigational product within the last 12 weeks

Sponsors & Collaborators

• Spark Therapeutics, Inc.: lead

Study Sites (16)

University of California Davis - Hemostasis and Thrombosis Center

Sacramento, California, 94817, United States

Location

University of Florida Health

Gainesville, Florida, 32610, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Mississippi Center for Advanced Medicine

Madison, Mississippi, 39110, United States

Location

Weill Cornell Medicine-Comprehensive Center for Hemophilia and Coagulation Disorders

New York, New York, 10065, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Pennsylvania State University Milton S. Hershey Medical Center

Hershey, Pennsylvania, 10733, 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

Royal Prince Alfred Hosptial

Camperdown, New South Wales, 2050, Australia

Location

The Alfred Hospital

Melbourne, 3004, Australia

Location

McMaster University Medical Centre and Juravinski Hospital

Hamilton, Ontario, L8N 3Z5, Canada

Location

Chaim Sheba Center

Ramat Gan, Tel Hashomer, 526000, Israel

Location

Mahidol University - Ramathibody Hospital

Bangkok, 10400, Thailand

Location

Related Publications (2)

• George LA, Monahan PE, Eyster ME, Sullivan SK, Ragni MV, Croteau SE, Rasko JEJ, Recht M, Samelson-Jones BJ, MacDougall A, Jaworski K, Noble R, Curran M, Kuranda K, Mingozzi F, Chang T, Reape KZ, Anguela XM, High KA. Multiyear Factor VIII Expression after AAV Gene Transfer for Hemophilia A. N Engl J Med. 2021 Nov 18;385(21):1961-1973. doi: 10.1056/NEJMoa2104205.

  PMID: 34788507 DERIVED

• Ran G, Chen X, Xie Y, Zheng Q, Xie J, Yu C, Pittman N, Qi S, Yu FX, Agbandje-McKenna M, Srivastava A, Ling C. Site-Directed Mutagenesis Improves the Transduction Efficiency of Capsid Library-Derived Recombinant AAV Vectors. Mol Ther Methods Clin Dev. 2020 Mar 13;17:545-555. doi: 10.1016/j.omtm.2020.03.007. eCollection 2020 Jun 12.

  PMID: 32258217 DERIVED

MeSH Terms

Conditions

Hemophilia A; Blood Coagulation Disorders; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; 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: Spark Therapeutics
• Organization: Spark Therapeutics

clinicaltrials@sparktx.com

Please Email

Study Officials

• Clinical Trial Director

  Spark Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2016
• First Posted: December 28, 2016
• Study Start: January 26, 2017
• Primary Completion: December 5, 2023
• Study Completion: December 5, 2023
• Last Updated: December 30, 2024
• Results First Posted: December 30, 2024

Record last verified: 2024-12

Locations

CA (1); TH (1); US (11); IL (1); AU (2)