Trial record 1 of 1 for:    NCT00979238
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Dose-Escalation Study Of A Self Complementary Adeno-Associated Viral Vector For Gene Transfer in Hemophilia B

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by St. Jude Children's Research Hospital
Sponsor:
Collaborators:
Hemophilia of Georgia, Inc.
Children's Hospital of Philadelphia
University of Kentucky
The Hemophilia Center of Western Pennsylvania
Oregon Health and Science University
University of Texas
Scott and White Hospital & Clinic
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00979238
First received: September 16, 2009
Last updated: June 23, 2014
Last verified: June 2014

September 16, 2009
June 23, 2014
August 2009
June 2015   (final data collection date for primary outcome measure)
To assess the safety of systemic administration of a novel self complementary AAV vector in adults with severe hemophilia B at up to four different dosage levels. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
To assess the safety of systemic administration of a novel self complementary AAV vector in adults with severe hemophilia B at up tp three different dosage levels. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00979238 on ClinicalTrials.gov Archive Site
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Dose-Escalation Study Of A Self Complementary Adeno-Associated Viral Vector For Gene Transfer in Hemophilia B
An Open Label Dose-Escalation Study Of A Self Complementary Adeno-Associated Viral Vector (scAAV 2/8-LP1-hFIXco) For Gene Transfer in Hemophilia B

The purpose of this study is to determine the safety of giving a normal factor IX gene to treat individuals who have an abnormal or no factor IX gene. Recruitment will be limited to adults (≥ 18 years) with a confirmed diagnosis of hemophilia B (HB), resulting from a missense mutation in the coagulation factor IX (FIX) gene or a nonsense mutation that has not been associated with an inhibitor. Only subjects who have no evidence of active hepatitis or anti-hFIX antibodies, and who have been treated/exposed to Factor IX concentrates for at least ten years and have had an average of 3 bleeding episodes per year requiring FIX administration will be enrolled. Patients will be recruited within the United States for treatment at one of two centers and patients will be recruited in England and other countries for treatment in London by our British collaborators.

Hemophilia B is caused by an absence or abnormality in the gene that produces the factor IX protein. Affected individuals cannot make a blood clot effectively and suffer from severe bleeding episodes. Repeated bleeding episodes, specifically into joints, can cause chronic joint disease and lead to disability. This research study will test the safety of giving an affected individual a normal factor IX gene which can produce factor IX protein in his body. We will give the normal gene for factor IX by using an inactivated (not able to function) virus called "the vector." The vector used in this study was developed from an adeno-associated virus that has been changed so that it is unable to cause a viral infection in humans. This inactivated virus was further altered to carry the factor IX gene and to locate within liver cells where factor IX protein is normally made.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Hemophilia B
Genetic: Gene Transfer
Peripheral vein infusion of scAAV2/8-LP1-hFIXco vector once per participant
1

All participants who meet the eligibility requirements.

Intervention: Gene Transfer

Intervention: Genetic: Gene Transfer
Nathwani AC, Tuddenham EG, Rangarajan S, Rosales C, McIntosh J, Linch DC, Chowdary P, Riddell A, Pie AJ, Harrington C, O'Beirne J, Smith K, Pasi J, Glader B, Rustagi P, Ng CY, Kay MA, Zhou J, Spence Y, Morton CL, Allay J, Coleman J, Sleep S, Cunningham JM, Srivastava D, Basner-Tschakarjan E, Mingozzi F, High KA, Gray JT, Reiss UM, Nienhuis AW, Davidoff AM. Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. N Engl J Med. 2011 Dec 22;365(25):2357-65. doi: 10.1056/NEJMoa1108046. Epub 2011 Dec 10.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
18
July 2029
June 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Males ≥ 18 years of age with established severe HB (FIX:C<1u/dl),
  • Treated/exposed to FIX products (e.g., concentrates or fresh frozen plasma) for at least 10 years or 50 exposure days.
  • A minimum of an average of 3 bleeding episodes per year requiring FIX infusions or prophylactic FIX infusions because of frequent prior bleeding episodes
  • Able to give informed consent and comply with requirements of the trial
  • Currently free of inhibitor and have no history of inhibitors to FIX protein
  • A negative family history for the development of an inhibitor,
  • Willing to practice a reliable barrier method of contraception until 3 sequential samples are negative for vector genomes using our PCR assay.

Exclusion Criteria:

  • Evidence of active infection with Hepatitis B or C virus as reflected by HBsAg or NCV RNA positivity, respectively. To be considered negative for active infection, two negative assays at a minimum of a six month interval are required.
  • Exposure to Hepatitis B or C who are currently on antiviral therapy.
  • Serological evidence of HTLV or active HIV infection. Individuals who are effectively being treated with antiretroviral therapy are eligible. Specific criteria for effectiveness of treatment include the following:

    • Documented CD4+ T-cell count of > 350 cells/mm^3.
    • HIV-1 RNA viral load < 400 copy/ml for at least the past 12 months, including at least 2 viral load test results of < 400 copy/ml during the immediate 12 month interval prior to screening.
    • Screening HIV-RNA viral load < 400 copies/ml.
    • Stable HAART regimen (drugs of at least 2 different classes) for at least 12 months prior to study entry. Treatment regimen changes for dosing convenience and in response to toxicity are permitted.
    • Documented and confirmed (repeated) viral loads of ≥ 400 copies/ml during the 12 month time interval prior to screening are bases for exclusion although a single, unconfirmed, "glimpse" of ≥ 400 copies/ml are permitted.
  • Significant liver dysfunction as defined by an abnormal ALT (alanine transaminase), bilirubin, alkaline phosphatase or INR. Potential participants who have had a liver biopsy in the past 3 years will be excluded if they have significant fibrosis of 3 or 4 as rated on a scale of 0-4.
  • Coronary artery disease as a co-morbid condition
  • Platelet count of <50 x 10^9/l
  • Creatinine ≥ 1.5 mg/dl
  • Hypertension with systolic blood pressure (BP) ≥ 140 mmHg or diastolic BP ≥ 90 mmHg
  • History of active tuberculosis, fungal disease or other chronic infection
  • History of chronic disease that would adversely affect performance other than hemophilic arthropathy
  • Detectable antibodies reactive with AAV8
  • Subjects who are unwilling to provide the required semen samples
  • Poor performance status (WHO performance status score >1) or
  • Received a gene transfer agent in the previous 6 months
Male
18 Years and older
No
Contact: Arthur W Nienhuis, MD 1-866-278-5833 info@stjude.org
United States,   United Kingdom
 
NCT00979238
AGT4HB, 5R01HL094396
Yes
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital
  • National Heart, Lung, and Blood Institute (NHLBI)
  • Hemophilia of Georgia, Inc.
  • Children's Hospital of Philadelphia
  • University of Kentucky
  • The Hemophilia Center of Western Pennsylvania
  • Oregon Health and Science University
  • University of Texas
  • Scott and White Hospital & Clinic
Principal Investigator: Arthur W Nienhuis, MD St. Jude Children's Research Hospital
St. Jude Children's Research Hospital
June 2014

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