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A Gene Transfer Study for Hemophilia A

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03003533
Recruitment Status : Recruiting
First Posted : December 28, 2016
Last Update Posted : May 15, 2020
Sponsor:
Information provided by (Responsible Party):
Spark Therapeutics

Tracking Information
First Submitted Date  ICMJE December 16, 2016
First Posted Date  ICMJE December 28, 2016
Last Update Posted Date May 15, 2020
Actual Study Start Date  ICMJE January 26, 2017
Estimated Primary Completion Date May 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 3, 2017)
  • Number of study-related adverse events, including clinically significant abnormal laboratory values [ Time Frame: 52 weeks ]
    adverse events
  • Changes from baseline in FVIII activity levels after a single outpatient administration of SPK-8011 [ Time Frame: 52 weeks ]
    changes in FVIII activity levels
Original Primary Outcome Measures  ICMJE
 (submitted: December 21, 2016)
  • Number of study-related adverse events, including clinically significant abnormal laboratory values [ Time Frame: 52 weeks ]
  • Changes from baseline in FVIII activity levels after a single outpatient administration of SPK-8011 [ Time Frame: 52 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 3, 2017)
  • Kinetic assessment of SPK-8011 including shedding of vector DNA in bodily fluids [ Time Frame: 52 weeks ]
    vector shedding
  • Number of participants requiring a course of steroid therapy for the elevations in liver enzymes [ Time Frame: 52 weeks ]
    number of participants requiring steroids
Original Secondary Outcome Measures  ICMJE
 (submitted: December 21, 2016)
  • Kinetic assessment of SPK-8011 including shedding of vector DNA in bodily fluids [ Time Frame: 52 weeks ]
  • Number of participants requiring a course of steroid therapy for the elevations in liver enzymes [ Time Frame: 52 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Gene Transfer Study for Hemophilia A
Official Title  ICMJE 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
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hemophilia A
Intervention  ICMJE Genetic: SPK-8011
A novel, bio-engineered, recombinant adeno-associated viral vector carrying human factor VIII gene
Study Arms  ICMJE Experimental: SPK-8011
All participants who meet the eligibility criteria will receive an outpatient single intravenous (i.v.) administration of SPK-8011.
Intervention: Genetic: SPK-8011
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 21, 2016)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2020
Estimated Primary Completion Date May 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Clinical Director 1-855-SPARKTX clinicaltrials@sparktx.com
Listed Location Countries  ICMJE Australia,   Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03003533
Other Study ID Numbers  ICMJE SPK-8011-101
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Spark Therapeutics
Study Sponsor  ICMJE Spark Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Lindsey George, MD Children's Hospital of Philadelphia
PRS Account Spark Therapeutics
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP