Clinical trial: Gene Therapy Study in Severe Hemophilia A Patients With Antibodies Against AAV5 (NCT03520712)

Eligibility criteria:
Inclusion Criteria:

          1. Males ≥ 18 years of age with hemophilia A and residual FVIII levels ≤ 1 IU/dL as
             evidenced by medical history, at the time of signing the informed consent.

          2. Detectable pre-existing antibodies against the AAV5 vector capsid as measured by AAV5
             total antibody ELISA.

          3. Subject must have been on prophylactic FVIII replacement therapy for at least 12
             months prior to study entry.

          4. No previous documented history of a detectable FVIII inhibitor, and results from a
             Bethesda assay or Bethesda assay with Nijmegen modification of less than 0.6 Bethesda
             Units (BU) (or less than 1.0 BU for laboratories with a historical lower sensitivity
             cutoff for inhibitor detection of 1.0 BU) on 2 consecutive occasions at least one week
             apart within the past 12 months (at least one of which should be tested at the central
             laboratory).

          5. Sexually active participants must agree to use an acceptable method of effective
             contraception. Participants must agree to contraception use for at least 12 weeks
             post-infusion.

        Exclusion Criteria:

          1. Any evidence of active infection including COVID-19, or any immunosuppressive
             disorder, including HIV infection.

          2. Evidence of liver dysfunction as assessed by liver tests and most recent, prior
             FibroScan or liver biopsy showing significant fibrosis of 3 or 4 as rated on a scale
             of 0-4 on the Batts-Ludwig (Batts 1995) or METAVIR (Bedossa 1996) scoring systems, or
             an equivalent grade of fibrosis if an alternative scale is used.

          3. Chronic or active hepatitis B or C as evidenced by testing at screening.

          4. Active malignancy, except non-melanoma skin cancer, or history of hepatic malignancy.

          5. Any condition that, in the opinion of the investigator or Sponsor would prevent the
             patient from fully complying with the requirements of the study (including
             corticosteroid treatment and/or use of alternative immunosuppressive agents outlined
             in the protocol) and/or would impact or interfere with evaluation and interpretation
             of subject safety or efficacy result.
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? 1