Safety and Efficacy Extension Study of GreenGene™ F in Previously Treated Patients Diagnosed With Severe Hemophilia A
Safety and Efficacy Extension Study of GreenGene™ F in Previously Treated Patients Diagnosed With Severe Hemophilia A
This study primarily will address the safety and secondarily will assess efficacy of
 GreenGene™ F in subjects with severe hemophilia A previously treated ≥50 exposure days with a
 GreenGene™ F, and without presence inhibitor to FVIII (Factor VIII).
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