Hemophilia B Gene Therapy With AAV8 Vector

This is an interventional treatment trial for Hemophilia B focused on measuring AAV, AAV8, Adeno-associated virus, Adeno-associated viral vectors, Hemophilia, Hemophilia B, Severe hemophilia B, Factor IX deficiency, Factor IX, FIX Read More

Inclusion Criteria:

• Willingness to adhere to the clinical protocol and 15-year long-term follow-up as evidenced by written informed consent
• Adult males at least 18 years of age
• A. Severe FIX deficiency (<1% normal circulating FIX) or B. Moderately severe FIX deficiency (1-2% normal circulating FIX, inclusive) and a severe bleeding phenotype as defined by at least one of the following: i. On prophylaxis for a history of bleeding or ii. On demand therapy with a current or past history of frequent bleeding [4 or more bleeding episodes in the last 12 months or chronic hemophilic arthropathy (pain, joint destruction, and loss of range of motion) in one or more joints]
• No history of inhibitor against FIX
• No history of an allergic reaction or anaphylaxis to FIX products
• Greater than 20 exposure days of treatment with FIX protein
• Anti-AAV8 neutralizing titer measured at < 1:5
• Acceptable laboratory values: hemoglobin ≥ 11% gm; WBC ≥ 3,500/μL; platelets ≥ 100,000/μL; AST, ALT, alkaline phosphatase ≤ 2x ULN; bilirubin ≤ 1.2 gm/dL; and creatinine ≤ 1.5 gm/dL
• Subject agrees to use barrier contraception until at least two consecutive semen samples after vector administration are negative for vector sequences (may be for up to several months)

Exclusion Criteria:

• Subjects with active hepatitis B or C, and HBsAg or HCV RNA viral load positivity, respectively. Negative viral assays in two samples, collected at least six months apart, will be required to be considered negative. Both natural clearers and those who have cleared HCV on antiviral therapy are eligible.
• Subjects currently on antiviral therapy for hepatitis B or C
• Subjects with significant underlying liver disease, as defined by presence of portal hypertension, splenomegaly, varices, ascites, edema, gastrointestinal bleeding, encephalopathy, reduction below normal limits of serum albumin, or prior liver biopsy demonstrating significant fibrosis, specifically ≥ Metavir 3 fibrosis
• Subjects with serological evidence of HIV who have CD4 counts ≤ 200/mm3. Subjects who are HIV-positive and stable, with an adequate CD4 count (> 200/mm3) and undetectable viral load (< 50 gc/mL) measured twice in the six months prior to enrollment, on an antiretroviral drug regimen are eligible to enroll.
• History of inhibitor against FIX
• Anti-AAV8 antibody titers ≥ 1:5
• History of chronic infection or other chronic diseases which the investigators consider to constitute an unacceptable risk
• Subjects who have participated in a previous gene therapy research trial within one year of enrollment
• Subjects who have participated in a clinical study with an investigational drug within six months of enrollment
• Any other condition that would not allow the potential subject to complete follow-up examinations during the course of the study or, in the opinion of the investigator, makes the potential subject unsuitable for the study