Status:
ACTIVE_NOT_RECRUITING
Dose-Escalation Study Of A Self Complementary Adeno-Associated Viral Vector For Gene Transfer in Hemophilia B
Lead Sponsor:
St. Jude Children's Research Hospital
Collaborating Sponsors:
National Heart, Lung, and Blood Institute (NHLBI)
Hemophilia of Georgia, Inc.
Conditions:
Hemophilia B
Eligibility:
MALE
18+ years
Phase:
PHASE1
Brief Summary
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...
Detailed Description
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....
Eligibility Criteria
Inclusion
- 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
- 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 an AAV vector or any other gene transfer agent in the previous 6 months
- Presence of lung nodule(s) suspicious of malignancy on screening chest tomography
- Presence of liver abnormalities suspicious of malignancy on screening liver ultrasound
Key Trial Info
Start Date :
February 22 2010
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
December 1 2025
Estimated Enrollment :
14 Patients enrolled
Trial Details
Trial ID
NCT00979238
Start Date
February 22 2010
End Date
December 1 2025
Last Update
September 19 2025
Active Locations (8)
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1
Stanford Medical School
Stanford, California, United States, 94305
2
University of Kentucky
Lexington, Kentucky, United States, 40536
3
Oregon Health and Science University
Portland, Oregon, United States, 97239
4
Hemophilia Center of Western Pennsylvania
Pittsburgh, Pennsylvania, United States, 15213