Clinical trial: Hemophilia B Gene Therapy With AAV8 Vector (NCT01620801)

Eligibility criteria:
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
Male
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.


Patient description (medical language): A 20-year-old man comes to the emergency due to bleeding after a tooth extraction.  The bleeding has persisted for approximately 30 minutes despite constant direct pressure.  He is a known case of Hemophilia type A treated with FVIII. Blood pressure is 95/60 mm Hg and pulse is 105/min. His weight is 70 Kg. Family history is positive for Hemophilia type A in his maternal uncle. He also has a lipoma on his left arm which he plans to remove surgically. His FVIII activity is 40%.

Patient description (patient's own words): I got my tooth extracted and I could not stop bleeding for 30 min. I'm a 20 yo dude but I have Hemophilia type A treated with FVIII. My blood pressure was 95/60 and my pulse 105/min. I'm 70 kg. My uncle on my mom's side also has type A hemophilia. I also have a fatty swelling on my left arm and I was supposed to remove it. My FVIII activity was 40%.

Does the patient match the trial criteria? Contradiction