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A Gene Transfer Study for Hemophilia A

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ClinicalTrials.gov Identifier: NCT03003533
Recruitment Status : Recruiting
First Posted : December 28, 2016
Last Update Posted : December 17, 2018
Sponsor:
Information provided by (Responsible Party):
Spark Therapeutics

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.

Condition or disease Intervention/treatment Phase
Hemophilia A Genetic: SPK-8011 Phase 1 Phase 2

Detailed Description:

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 treatment is intravenous (i.v.) injections of factor VIII protein products, either 2-3 times weekly or in response to bleeding.

Recent preliminary clinical data of a hemophilia B gene transfer study (which is also being conducted by Spark Therapeutics) shows all study participants achieving therapeutic factor IX activity levels (average of maintaining factor IX activity levels around 30% of normal with no confirmed bleeds, after receiving Spark gene transfer, with the approach of using the novel bio-engineered recombinant adeno-associated viral (rAAV) vector carrying a high specific activity of a factor IX gene. The approach being tested in this clinical research study uses a further modified novel AAV vector (with a stronger attraction to the human liver) to deliver the human factor VIII (hFVIII) gene into liver cells so that they can produce factor VIII protein.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Gene Transfer, Dose-Finding Safety, Tolerability, and Efficacy Study of SPK-8011 [a Recombinant Adeno-Associated Viral Vector With Human Factor VIII Gene] in Individuals With Hemophilia A
Study Start Date : December 2016
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : December 2019


Arm Intervention/treatment
Experimental: SPK-8011
All participants who meet the eligibility criteria will receive an outpatient single intravenous (i.v.) administration of SPK-8011.
Genetic: SPK-8011
A novel, bio-engineered, recombinant adeno-associated viral vector carrying human factor VIII gene




Primary Outcome Measures :
  1. Number of study-related adverse events, including clinically significant abnormal laboratory values [ Time Frame: 52 weeks ]
    adverse events

  2. Changes from baseline in FVIII activity levels after a single outpatient administration of SPK-8011 [ Time Frame: 52 weeks ]
    changes in FVIII activity levels


Secondary Outcome Measures :
  1. Kinetic assessment of SPK-8011 including shedding of vector DNA in bodily fluids [ Time Frame: 52 weeks ]
    vector shedding

  2. Number of participants requiring a course of steroid therapy for the elevations in liver enzymes [ Time Frame: 52 weeks ]
    number of participants requiring steroids



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males age18 years or older
  • Confirmed diagnosis of hemophilia A as evidenced by their medical history with plasma FVIII activity levels ≤ 2% of normal
  • Have received >150 exposure days (EDs) to FVIII concentrates or cryoprecipitate
  • Have experienced >10 bleeding events over the previous 12 months only if receiving on-demand therapy and having FVIII baseline level 1-2% of normal
  • Have no prior history of allergic reaction to any FVIII product
  • Have no measurable inhibitor against Factor VIII as assessed by the central laboratory and have no prior history of inhibitors to FVIII protein
  • 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 (* 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03003533


Contacts
Contact: Clinical Director clinicaltrials@sparktx.com

Locations
United States, California
University of California Davis - Hemostasis and Thrombosis Center Recruiting
Sacramento, California, United States, 94817
Contact: Adam Giermasz, MD, PhD    916-734-1293    giermasz@ucdavis.edu   
Contact: Erika Adams    (916) 734-7633    ejadams@ucdavis.edu   
United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Stacey Croteau, MD       Stacy.Croteau@childrens.harvard.edu   
Contact: Felicia Ciuculescu    617-632-1955    Felicia.Ciuculescu@childrens.harvard.edu   
United States, Mississippi
Mississippi Center for Advanced Medicine Recruiting
Madison, Mississippi, United States, 39110
Contact: Spencer K. Sullivan, MD    601-499-0935    SKSullivan@msadvancedmedicine.com   
United States, New York
Weill Cornell Medicine-Comprehensive Center for Hemophilia and Coagulation Disorders Recruiting
New York, New York, United States, 10065
Contact: Catherine McGuinn, MD    212-746-3978    cam9061@med.cornell.edu   
Contact: Ilene Goldberg, RN       igoldber@med.cornell.edu   
United States, North Carolina
East Carolina University Withdrawn
Greenville, North Carolina, United States, 27858
United States, Pennsylvania
Pennsylvania State University Milton S. Hershey Medical Center Recruiting
Hershey, Pennsylvania, United States, 10733
Contact: Elaine Eyster, MD       meyster@hmc.psu.edu   
Contact: Gail Long    717-531-6603    glong@hmc.psu.edu   
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Lindsey George, MD       GeorgeL@email.chop.edu   
Contact: Ben Samelson-Jones, MD, PhD       SamelsonJonesB@email.chop.edu   
Hemophilia Center of Western Pennsylvania Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Judith Kadosh, RN, BSN    412-209-7263    JKadosh@itxm.org   
Contact: Margaret V Ragni, MD         
United States, Virginia
Virginia Commonwealth University School of Medicine Recruiting
Richmond, Virginia, United States, 23219
Contact: J Christian Barrett, MD    804-827-3306    jcbarrett@vcu.edu   
Contact: Janice Kuhn    804-827-3306    janice.kuhn@vcuhealth.org   
Australia, New South Wales
Royal Prince Alfred Hosptial Recruiting
Camperdown, New South Wales, Australia, 2050
Contact: John Rasko, MD    +029 5656156    j.rasko@centenary.usyd.edu.au   
Canada, Ontario
St. Michael's Hospital Withdrawn
Toronto, Ontario, Canada, M5B 1W8
Sponsors and Collaborators
Spark Therapeutics
Investigators
Study Director: Clinical Director Spark Therapeutics

Responsible Party: Spark Therapeutics
ClinicalTrials.gov Identifier: NCT03003533     History of Changes
Other Study ID Numbers: SPK-8011-101
First Posted: December 28, 2016    Key Record Dates
Last Update Posted: December 17, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Spark Therapeutics:
Blood Coagulation Disorders
Blood Coagulation Disorders, Inherited
Coagulation Protein Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Hematologic Diseases
Hemorrhagic Disorders
Adeno-Associated Virus (AAV)
Factor VIII (FVIII)
Factor VIII (FVIII) Deficiency
Factor VIII (FVIII) Gene
Factor VIII (FVIII) Protein
Gene Therapy
Gene Transfer
Recombinant
Vector

Additional relevant MeSH terms:
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Coagulants