Clinical trial: Safety and Efficacy Extension Study of GreenGene™ F in Previously Treated Patients Diagnosed With Severe Hemophilia A (NCT02027779)

Eligibility criteria:
Inclusion Criteria:

          1. Subjects must have participated in the "GreenGene™ F_P3", (with Eudra CT number
             2012-001445-40) or a pediatric study with GreenGene™ F

          2. Have ≥50 previous exposure days to GreenGene™ F, as documented in the subject's
             medical records.

          3. Negative assays for FVIII inhibitor at inclusion (<0.6BU Nijmegen assay), i.e. at the
             end of study "GreenGene™ F_P3" for patients entering into this extension study
             immediately after finishing the previous phase III study.

          4. Normal liver and kidney function

          5. Platelet count ≥ 100,000㎕

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

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

          8. Subjects must be able to withhold FVIII infusions for approximately 72 h prior to each
             inhibitor assay

          9. Absolute CD4 lymphocyte cell count ≥ 200㎕

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

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

         12. All females will be considered to be of childbearing potential unless they are
             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)

         13. 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.

          2. 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 of physical
             examination and/or a history of esophageal hemorrhage or documented esophageal varices

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

          4. Hemoglobin < 10 g/dL

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

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

          7. History of diabetes or other metabolic disease

          8. History of hypersensitivity or serious adverse reaction to recombinant or
             plasma-derived FVIII concentrates

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

         10. Regular use of antifibrinolytics or medications affecting platelet function

         11. Hypersensitivity to hamster- or mouse derived proteins

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

         13. 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

         14. Unable or unwilling to cooperate with study procedures

         15. Females who are pregnant (positive β-hCG test) or breastfeeding
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.



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