A Gene Transfer Study for Hemophilia A

NCT ID: NCT03003533

Last Updated: 2024-12-30

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

25 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-01-26

Study Completion Date

2023-12-05

Brief Summary

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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.

Detailed Description

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Hemophilia A is a condition in which blood is unable to clot effectively. It is caused by a mutation or deletion in the gene that is responsible for producing blood-clotting factor VIII protein. Individuals with hemophilia A suffer from repeated bleeding episodes, often into the joints, which can cause chronic joint disease and sometime results in death due to the inability of the blood to clot efficiently. This chronic joint disease can have significant physical, psychosocial, and quality-of-life effects, including financial burden. The current standard of care includes the use of factor-based therapies which are given either as prophylaxis or to treat bleeding, as well as new non-factor prophylaxis therapies.

Conditions

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Hemophilia A

Keywords

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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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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SPK-8011 5x10^11 vg/kg

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

Group Type EXPERIMENTAL

SPK-8011

Intervention Type GENETIC

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

SPK-8011 1x10^12 vg/kg

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

Group Type EXPERIMENTAL

SPK-8011

Intervention Type GENETIC

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

SPK-8011 2x10^12 vg/kg

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

Group Type EXPERIMENTAL

SPK-8011

Intervention Type GENETIC

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

SPK-8011 1.5x10^12 vg/kg

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

Group Type EXPERIMENTAL

SPK-8011

Intervention Type GENETIC

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

Interventions

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SPK-8011

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

Intervention Type GENETIC

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Spark Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trial Director

Role: STUDY_DIRECTOR

Spark Therapeutics, Inc.

Locations

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University of California Davis - Hemostasis and Thrombosis Center

Sacramento, California, United States

Site Status

University of Florida Health

Gainesville, Florida, United States

Site Status

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status

Mississippi Center for Advanced Medicine

Madison, Mississippi, United States

Site Status

Weill Cornell Medicine-Comprehensive Center for Hemophilia and Coagulation Disorders

New York, New York, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

Pennsylvania State University Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Jefferson University Hospitals

Philadelphia, Pennsylvania, United States

Site Status

Hemophilia Center of Western Pennsylvania

Pittsburgh, Pennsylvania, United States

Site Status

Virginia Commonwealth University School of Medicine

Richmond, Virginia, United States

Site Status

Royal Prince Alfred Hosptial

Camperdown, New South Wales, Australia

Site Status

The Alfred Hospital

Melbourne, , Australia

Site Status

McMaster University Medical Centre and Juravinski Hospital

Hamilton, Ontario, Canada

Site Status

Chaim Sheba Center

Ramat Gan, Tel Hashomer, Israel

Site Status

Mahidol University - Ramathibody Hospital

Bangkok, , Thailand

Site Status

Countries

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United States Australia Canada Israel Thailand

References

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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.

Reference Type DERIVED
PMID: 34788507 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32258217 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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SPK-8011-101

Identifier Type: -

Identifier Source: org_study_id