Safety, Efficacy and Pharmacokinetics of GreenGene™ F to Previously Treated Patients With Severe Hemophilia A
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The purpose of this study is to assess the safety, efficacy and pharmacokinetics of GreenGene™ F in subjects with severe hemophilia A previously treated (> 150 exposure days) with a Factor VIII concentrate and without presence or history of inhibitors to FVIII (Factor VIII).
Condition | Intervention | Phase |
---|---|---|
Hemophilia A |
Biological: GreenGeneF, An approved recombinant Factor VIII product Biological: GreenGeneF |
Phase 3 |
Study Type: | Interventional |
Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
Official Title: | Determination of Safety, Efficacy and Pharmacokinetics of GreenGene™ F in Previously Treated Patients 12 Years of Age or Older Diagnosed With Severe Hemophilia A |
- Area under the plasma concentration versus time curve (AUC) of 'GreenGeneF' [ Time Frame: 0~48 hours post dose ] [ Designated as safety issue: No ]
- Number of subject with development of inhibitors [ Time Frame: every 3 months, up to 18months ] [ Designated as safety issue: Yes ]Development of neutralizing antibodies (inhibitors) will be followed during the regular visits, average of 3 months.
Estimated Enrollment: | 124 |
Study Start Date: | June 2012 |
Estimated Primary Completion Date: | October 2013 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
---|---|
Active Comparator: PK substudy
A cohort of 13-18 subjects will be included in the pharmacokinetic (PK) evaluation; a minimum of 13 of these subjects will be re-evaluated at study end(50 exposure day).
|
Biological: GreenGeneF, An approved recombinant Factor VIII product
one 50 IU/kg, intra venous infusion over 5 minutes, Infusion rate < 10 mL/min
|
Experimental: Prophylaxis safety and efficacy substudy
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 exposure days.
|
Biological: GreenGeneF
intra venous infusion, 30 ± 5 IU/kg infusions 3 times per week with dose escalation to 45 ± 5 IU/kg if appropriate, for 50 exposure days
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Experimental: On-demand safety and efficacy substudy
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 50 exposure days.
|
Biological: GreenGeneF
intra venous infusion, On-demand safety and efficacy substudy: minor bleed = 10-20 IU/kg moderate bleed = 15-30 IU/kg major bleed = 30-50 IU/kg |
Experimental: Surgical substudy
Peri-operative hemostatic control of GreenGene™ F in surgery or invasive procedures will be assessed in at least 10 surgeries, some of them major, in at least five subjects
|
Biological: GreenGeneF
intra venous infusion, Surgical substudy: Minor surgery including tooth extraction = Post in fusion FVIII level of 60-100% of normal. A single bolus infusion (30-50 IU/kg) beginning within one hour of the operation. Optional additional dosing every 12 to 24 hours as needed to control bleeding. Major surgery = Pre- and post infusion FVIII level 80-120% of normal. Preoperative bolus infusion: 40-60 IU/kg. Verified 100% activity prior to surgery. Maintenance bolus infusion (40-60 IU/kg) repeat infusions every 8 to 24 hours, depending on the desired level. |
Ages Eligible for Study: | 12 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Male or female subjects age ≥ 12 years at the time of informed consent
- Body weight ≥ 35 kg
- Diagnosed with severe hemophilia A. All subjects must have severe hemophilia A with baseline FVIII < 1 IU/mL.
- Have ≥ 150 previous exposure days to FVIII concentrates, as documented in the subject's medical records
- 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
- Negative assays for FVIII inhibitor at both local and central laboratories at inclusion (<0.6BU Nijmegen assay)
- Negative assays for FVIII inhibitor in subject files (<0.6BU Nijmegen assay) No history of positive inhibitor is allowed
- Normal liver and kidney function.
- Platelet count ≥ 100,000 μL
- Normal prothrombin time or International Normalized Ratio (INR) < 1.5
- Subjects receiving therapy for human immunodeficiency virus (HIV) or hepatitis must be on a stable treatment regimen
- Subjects must be able to withhold FVIII infusions for approximately 72 h prior to each FVIII activity and inhibitor assay
- Absolute CD4 lymphocyte cell count ≥ 200 μL
Exclusion Criteria:
- 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
- History of FVIII inhibitor of ≥ 0.6 BU as measured using the Nijmegen modification of the Bethesda assay
- 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 treatment
- Demonstrated an inability to respond to conventional doses of FVIII therapy
- History of incremental recovery of Factor VIII <1.35% per IU/kg infused
- Hematological disorders or blood coagulation diseases (e.g., idiopathic thrombocytopenic purpura, von Willebrand disease, etc.) other than hemophilia A
- 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
- Uncontrolled hypertension (diastolic blood pressure >100 mm Hg)
- Hemoglobin < 10 g.dL
- HIV disease symptoms regardless of presence of HIV antibodies
- Routine administration (or planned routine administration during the course of the study), of immunosuppressive or immunomodulating drugs other than anti-retroviral therapy (e.g., steroids, beta-interferon)
- Severe renal dysfunction (creatinine > 2x upper limit of normal [ULN], total bilirubin > 2x the ULN)
- Liver disease (alanine aminotransferase [ALT], aspartate aminotransferase [ AST] > 3x the ULN)
- History of diabetes or other metabolic disease
- History of hypersensitivity or serious adverse reaction to recombinant or plasma-derived FVIII concentrate
- History of pretreatment prior to the administration of FVIII products (e.g., of antihistamines)
- Regular use of antifibrinolytics or medications affecting platelet function
- Hypersensitivity to hamster-or mouse derived proteins
- Blood transfusions within 30 days of enrollment into the study
Contact: Ho Young Lee | +82-10-5454-1159 | hoyoung.lee@greencross.com |
Principal Investigator: | Paul LeoFrancis Giangrande, MD | Oxford Haemophilic Centre and Thrombosis Unit, Churchill Hospital |
No publications provided
Responsible Party: | Green Cross Corporation |
ClinicalTrials.gov Identifier: | NCT01619046 History of Changes |
Other Study ID Numbers: | GreenGeneF_P3 |
Study First Received: | May 31, 2012 |
Last Updated: | June 12, 2012 |
Health Authority: | United States: Food and Drug Administration |
Keywords provided by Green Cross Corporation:
GreenGene™F, Previously Treated Patients |
Additional relevant MeSH terms:
Hemophilia A Blood Coagulation Disorders, Inherited Blood Coagulation Disorders Hematologic Diseases Coagulation Protein Disorders Hemorrhagic Disorders |
Genetic Diseases, Inborn Factor VIII Coagulants Hematologic Agents Therapeutic Uses Pharmacologic Actions |
ClinicalTrials.gov processed this record on October 17, 2012