Clinical trial: Safety, Efficacy and Pharmacokinetics of GreenGene™ F to Previously Treated Patients With Severe Hemophilia A (NCT01619046)

Eligibility criteria:
Inclusion Criteria:

          1. Male or female subjects age ≥ 12 years at the time of informed consent

          2. Body weight ≥ 35 kg

          3. Diagnosed with severe hemophilia A. All subjects must have severe hemophilia A with
             baseline FVIII <1% activity; <0.01 IU/mL

          4. Have ≥ 150 previous exposure days to FVIII concentrates, as documented in the
             subject's medical records

          5. Subjects included in the on-demand treatment cohort must have a verifiable record of
             at least three bleeding episodes per month on average in the last 6 months prior to
             enrollment

          6. Negative assays for FVIII inhibitor at inclusion (<0.6BU Nijmegen assay)

          7. Negative assays for FVIII inhibitor in subject files (<0.6BU Nijmegen assay) No
             history of positive inhibitor is allowed

          8. Normal liver and kidney function.

          9. Platelet count ≥ 100,000 μL

         10. Normal prothrombin time or International Normalized Ratio (INR) < 1.5

         11. Subjects receiving therapy for human immunodeficiency virus (HIV) or hepatitis must be
             on a stable treatment regimen

         12. Subjects must be able to withhold FVIII infusions for approximately 72 h prior to each
             FVIII activity and inhibitor assay (96 h if participating in the PK sub study)

         13. Absolute CD4 lymphocyte cell count ≥ 200 μL

         14. Signed the written informed consent form or informed consent was obtained from the
             subject's legal guardian

         15. Females must not be lactating or pregnant at Screening or Baseline (as documented by a
             negative beta-human chorionic gonadotropin [ß hCG] test with a minimum sensitivity of
             25 IU/L or equivalent units of ß hCG). A separate baseline assessment is required if a
             negative screening pregnancy test was obtained more than 72 hours before the first
             dose of study drug

         16. All females will be considered to be of childbearing potential unless they are
             postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age
             group and without other known or suspected cause) or have been sterilized surgically
             (i.e. bilateral tubal ligation, total hysterectomy or bilateral oophorectomy, all with
             surgery at least one month before dosing)

         17. Willing and able to comply with all aspects of the protocol

        Exclusion Criteria:

          1. Presence at Screening of FVIII inhibitor ≥ 0.6 BU as tested with the Nijmegen
             modification of the Bethesda assay in either central or local laboratory

          2. History of FVIII inhibitor of ≥ 0.6 BU as measured using the Nijmegen modification of
             the Bethesda assay

          3. History of FVIII inhibitor ≥ 1.0 BU if the subject has been tested routinely using the
             original Bethesda assay, or history of periods with low recovery and no response to
             Factor VIII treatment

          4. Demonstrated an inability to respond to conventional doses of FVIII therapy

          5. History of incremental recovery of Factor VIII <1.35% per IU/kg infused

          6. Hematological disorders or blood coagulation diseases (e.g., idiopathic
             thrombocytopenic purpura, von Willebrand disease, etc.) other than hemophilia A

          7. Laboratory or clinical evidence of portal vein hypertension including,(but not limited
             to, an INR > 1.4, the presence of splenomegaly and/or spider angiomata on physical
             examination and/or a history of esophageal hemorrhage or documented esophageal varices

          8. Uncontrolled hypertension (diastolic blood pressure >100 mm Hg)

          9. Hemoglobin < 10 g.dL

         10. HIV disease symptoms regardless of presence of HIV antibodies

         11. Routine administration (or planned routine administration during the course of the
             study), of immunosuppressive or immunomodulating drugs other than antiretroviral
             therapy (e.g., steroids, beta-interferon)

         12. Severe renal dysfunction (creatinine > 2x upper limit of normal [ULN], total bilirubin
             > 2x the ULN)

         13. Liver disease (alanine aminotransferase [ALT], aspartate aminotransferase [ AST] > 3x
             the ULN)

         14. History of diabetes or other metabolic disease

         15. History of hypersensitivity or serious adverse reaction to recombinant or
             plasma-derived FVIII concentrate

         16. History of pretreatment prior to the administration of FVIII products (e.g., of
             antihistamines)

         17. Regular use of antifibrinolytics or medications affecting platelet function

         18. Hypersensitivity to hamster-or mouse derived proteins

         19. Blood transfusions within 30 days of enrollment into the study

         20. Current participation in another investigational drug or device study, or participated
             in a clinical study involving an investigational drug or device within 30 days of
             enrollment into the study

         21. Unable or unwilling to cooperate with study procedures
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 12 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