Clinical trial NCT01619046: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Hemophilia A
Keywords: GreenGene™F, Previously Treated Patients
Lead sponsor: GC Biopharma Corp
Sponsor class: INDUSTRY
Collaborators: name: Atlantic Research Group
First posted: 2012-06-14
Enrollment: 124
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Number of subject with development of inhibitors
timeFrame: evert 3 months, up to 18 months
Secondary outcomes:
measure: Describe the PK profile of GreenGene™ F
timeFrame: Pre-dose, 0~48hours post-dose
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Los Angeles
country: United States
facility: Los Angeles Orthopaedic Hospital - Hemophilia Treatment Center
state: California
city: Torrance
country: United States
facility: Harbor - UCLA Pediatrics
state: California
city: Miami
country: United States
facility: University of Miami - Comprehensive Hemophilia Center
state: Florida
city: Boise
country: United States
facility: St. Luke's Boise Medical Center
state: Idaho
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: East Lansing
country: United States
facility: Michigan State University Center for Bleeding Disorders & Clotting Disorders
state: Michigan
city: Kansas City
country: United States
facility: Children's Mercy Hospital - Kansas City Regional Hemophilia Center
state: Missouri
city: New Hyde Park
country: United States
facility: Long Island Jewish Medical Center - Hemophilia Treatment Center
state: New York
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Hamilton
country: Canada
facility: McMaster Children's Hospital
state: Ontario
city: Christchurch
country: New Zealand
facility: Research Associates, Ltd.
city: Warszawa
country: Poland
facility: Instytut Hematologii i Transfuzjologii
city: Łodzi
country: Poland
facility: wojewodzki szpital Specjalistyczny, klinika hematologii uniwersytetu medycznego w łodzi
city: Barnaul
country: Russian Federation
facility: Barnaul Altai State Scientfic Center
city: Kirov
country: Russian Federation
facility: Kirov Research Institute of Hematology and Blood Transfusion
city: Moscow
country: Russian Federation
facility: Ismailov City Children's Clinical Hospital of Board of Health of Moscow City
city: Samara
country: Russian Federation
facility: State Budget Educational Institution of Higher professional Education "Samara State Medical University" of the Ministry of Health and Social Process of the Russian Federation
city: Ufa
country: Russian Federation
facility: Ufa Republican Clinical Hospital
city: Dnepropetrovsk
country: Ukraine
facility: Dnepropetrovsk City Clinical Hospital
city: Donetsk
country: Ukraine
facility: Institute of Urgent and Reconstructive surgery named after V.K. Gusak of National Academy of Medical Sciences of Ukraine
city: Kharkov
country: Ukraine
facility: Kharkov Regional Clinical Oncology Center
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Hospital No 91
city: Lviv
country: Ukraine
facility: Institute of Blood Pathology and Transfusion Medicine of National Academy of Medical Sciences of Ukraine Department of Surgery and Clinical Transfusiology
city: Zaporzhye
country: Ukraine
facility: Zaporizhzhya Region Clinical Child Hospital
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital, Department of Haematology
state: Cornwall
city: Humberside
country: United Kingdom
facility: Hull Haemophillia Centre, Hull Royal Infirmary
state: Hull
city: Manchester
country: United Kingdom
facility: Central Manchester University Hospitals
state: Lancashire
city: Westminster
country: United Kingdom
facility: St. Thomas' Hospital
state: London
city: Basingstoke
country: United Kingdom
facility: North Hampshire Haemophilia Centre
state: North Hampshire
city: Liverpool
country: United Kingdom
facility: University of Liverpool
city: London
country: United Kingdom
facility: Royal Free Hospital, Haemophilia Centre & Thrombosis Unit
city: Oxford
country: United Kingdom
facility: Churchill Hospital, Oxford
Study officials:
affiliation: Oxford Haemophilic Centre and Thrombosis Unit, Churchill Hospital
name: Paul LeoFrancis Giangrande, MD
role: PRINCIPAL_INVESTIGATOR
References: