Brief Title
Safety, Efficacy and Pharmacokinetics of GreenGene™ F to Previously Treated Patients With Severe Hemophilia A
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
Brief Summary
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).
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
Number of subject with development of inhibitors
Secondary Outcome
Describe the PK profile of GreenGene™ F
Condition
Hemophilia A
Intervention
GreenGene™ F and an approved recombinant Factor VIII product
Study Arms / Comparison Groups
PK substudy
Description: A cohort of 13-18 subjects will be included in the pharmacokinetic (PK) evaluation of GreenGene™ F and an approved recombinant Factor VIII product (Refacto AF); a minimum of 13 of these subjects will be re-evaluated at study end (50 exposure day).
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
124
Start Date
March 2013
Completion Date
September 2015
Primary Completion Date
July 2015
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
Gender
All
Ages
12 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Paul LeoFrancis Giangrande, MD, 540-649-5490, [email protected]
Location Countries
Canada
Location Countries
Canada
Administrative Informations
NCT ID
NCT01619046
Organization ID
GreenGeneF_P3
Responsible Party
Sponsor
Study Sponsor
Green Cross Corporation
Collaborators
Atlantic Research Group
Study Sponsor
Paul LeoFrancis Giangrande, MD, Principal Investigator, Oxford Haemophilic Centre and Thrombosis Unit, Churchill Hospital
Verification Date
July 2014