Clinical trial: Gene Therapy for Chinese Hemophilia A (NCT04728841)

Eligibility criteria:
Inclusion Criteria:

          1. Be able to understand the purpose and risks of the study and provide signed and dated
             informed consent and authorization to use protected health information (PHI) in
             accordance with national and local privacy regulations;

          2. Be male and ≥18 years of age;

          3. Endogenous FVIII activity levels<1iu. as documented by a certified clinical laboratory
             at the time of screening.

          4. Prior FVIII exposure days (EDs) ≥150 days of any recombinant and/or plasma-derived
             FVIII protein products based on historical data from the subject's record/history;

          5. a. Prophylaxis subjects: have had bleeding events and/or infusions with FVIII protein
             products during the last 12 weeks documented in the subjects' medical records; OR b.
             On-demand subjects: have had ≥4 bleeding events in the last 52 weeks and/or chronic
             hemophilic arthropathy (pain, joint destruction, and loss of range of motion) in one
             or more joints;

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

          7. Have no measurable FVIII inhibitor as assessed by laboratory; or documented no prior
             history of FVIII inhibitor after 150 EDs (family history of inhibitors will not
             exclude the subject) and no clinical signs or symptoms of decreased response to FVIII
             administration;

          8. Have acceptable laboratory values:

               1. Hemoglobin ≥11 g/dL;

               2. Platelets ≥100,000 cells/μL;

               3. Aspartate Transaminase（AST）, alanine aminotransferase （ALT）, alkaline phosphatase
                  ≤2x upper limit of normal at the testing laboratory;

               4. Bilirubin ≤3x upper limit of normal（ULN）;

               5. Creatinine ≤2.0 mg/dL.

          9. Agree to use reliable barrier contraception until three consecutive semen samples
             after the administration of GS001 are negative for vector sequences.

             -

        Exclusion Criteria:

          1. HBsAg or hepatitis B core antibody or hepatitis B virus-DNA positivity or hepatitis C
             virus-RNA viral load positivity. Negative viral assays in two samples, collected at
             least six months apart, will be required to be considered negative. Both natural
             clearer and those who have cleared hepatitis C virus on antiviral therapy are
             eligible;

          2. Currently on antiviral therapy for hepatitis B or C;

          3. Have significant underlying liver disease, as defined by a preexisting diagnosis of
             portal hypertension, splenomegaly, encephalopathy, reduction below normal limits of
             serum albumin or evidence of significant liver fibrosis (fibrosis stage ≥ 3) within
             the past 6 months prior to or at screening as determined by any of the following
             diagnostic modalities: AST-to-Platelet Ratio Index (APRI) >1;

          4. Have serological evidence of HIV-1 or HIV-2 with 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;

          5. Anti-GS001 neutralizing antibody titers ≥1:5;

          6. History of chronic infection or other chronic disease that the Investigator considers
             to constitute an unacceptable risk;

          7. Participated in a previous gene therapy research trial within the last 52 weeks or in
             a clinical study with an investigational drug within the last 12 weeks;

          8. Any concurrent clinically significant major disease or any other condition that, in
             the opinion of the Investigator, makes the subject unsuitable for participation in the
             study;

          9. Bad compliance.
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? Entailment