Safety and Efficacy Extension Study of GreenGene™ F in Previously Treated Patients Diagnosed With Severe Hemophilia A

Green Cross Corporation

Status and phase: Unknown; Phase 3

Conditions: Hemophilia A

Treatments: Biological: GreenGene™ F

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02027779

GreenGene™ F_E_P3

Details and patient eligibility

About

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).

Enrollment: 150 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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150 participants in 2 patient groups

Prophylaxis safety and efficacy substudy

Experimental group

Description:

Hemostatic efficacy of GreenGene™ F will be assessed by its effectiveness in controlling spontaneous or traumatic bleeding episodes and by the rate of breakthrough bleeding during prophylaxis over ≥ 50 additional exposure days.

Treatment:

Biological: GreenGene™ F

Biological: GreenGene™ F

On-demand safety and efficacy substudy

Experimental group

Description:

Hemostatic efficacy of GreenGene™ F will be assessed by its effectiveness in controlling spontaneous or traumatic bleeding episodes and by the rate of breakthrough bleeding in a minimum of 10 on demand treated subjects during additional 50 exposure days.

Treatment:

Biological: GreenGene™ F

Biological: GreenGene™ F