Clinical trial: Dose-finding Study of SPK-8016 Gene Therapy in Patients With Hemophilia A to Support Evaluation in Individuals With FVIII Inhibitors (NCT03734588)

Eligibility criteria:
Inclusion Criteria for Part 1:

          1. Be male and ≥18 years of age;

          2. Have clinically severe hemophilia A, defined as:

               1. <1% (<1 IU/dL) endogenous FVIII activity levels as historically documented by a
                  certified laboratory or screening data results; OR

               2. 1-2% (1-2 IU/dL) endogenous FVIII activity levels and > 10 bleeding events per
                  year (in the last 52 weeks prior to screening); OR

               3. 1-2% (1-2 IU/dL) endogenous FVIII activity levels and on prophylaxis;

          3. Have had >150 exposure days (EDs) to any recombinant and/or plasma-derived FVIII
             concentrates or cryoprecipitates

          4. Have no prior history of hypersensitivity or anaphylaxis associated with any FVIII or
             IV immunoglobulin administration

          5. Have no measurable inhibitor against FVIII as assessed by central laboratory, have no
             confirmed history of clinically significant FVIII inhibitor, and no clinical signs or
             symptoms of decreased response to FVIII administration (Note: family history of
             inhibitors will not exclude study participation)

          6. Agree to use reliable barrier contraception after the administration of SPK-8016 until
             notified by the Investigator.

        Exclusion Criteria for Part 1:

          1. Have active hepatitis B or C

          2. Have significant underlying liver disease.

          3. Have serological evidence of HIV-1 or HIV-2 with CD4 counts ≤200/mm3. Participants who
             are HIV-positive and stable, with an adequate CD4 count (>200/mm3) and undetectable
             viral load, and are on an antiretroviral drug regimen are eligible to enroll

          4. Have detectable antibodies reactive with AAV-Spark capsid

          5. Have history of chronic infection or other chronic disease

          6. Have been dosed in a previous gene therapy research trial within the last 52 weeks or
             with an investigational drug within the last 12 weeks

          7. Any concurrent clinically significant major disease (such as liver abnormalities or
             type I diabetes) or other condition that, in the opinion of the Investigator and/or
             Sponsor, makes the subject unsuitable for participation in the study;

          8. Unable or unwilling to comply with the schedule of visits and study assessments
             described in the clinical protocol.
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