Safety, Efficacy and Pharmacokinetics of GreenGene™ F to Previously Treated Patients With Severe Hemophilia A

This study is currently recruiting participants.
Verified January 2014 by Green Cross Corporation
Sponsor:
Collaborator:
Atlantic Research Group
Information provided by (Responsible Party):
Green Cross Corporation
ClinicalTrials.gov Identifier:
NCT01619046
First received: May 31, 2012
Last updated: January 2, 2014
Last verified: January 2014
  Purpose

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: GreenGene™ F and an approved recombinant Factor VIII product
Biological: GreenGene™ F
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

Resource links provided by NLM:


Further study details as provided by Green Cross Corporation:

Primary Outcome Measures:
  • Area under the plasma concentration versus time curve (AUC) of 'GreenGeneF' [ Time Frame: 0~48 hours post dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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: March 2013
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: July 2015 (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 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).
Biological: GreenGene™ F and an approved recombinant Factor VIII product
one 50 IU/kg, intra venous infusion over 5 minutes, Infusion rate < 10 mL/min
Other Names:
  • GreenGeneF
  • GreenGene F
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: GreenGene™ F
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
Other Names:
  • GreenGeneF
  • GreenGene F
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: GreenGene™ F

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

Other Names:
  • GreenGeneF
  • GreenGene F
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: GreenGene™ F

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.

Other Names:
  • GreenGeneF
  • GreenGene F

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01619046

Contacts
Contact: Kevin Wait 540-649-5490 kwait@atlanticresearchgroup.com

Locations
United States, Arkansas
Arkansas Children's Hospital Recruiting
Little Rock, Arkansas, United States, 72202
Contact: Bryce Warren       WarrenBryceA@uams.edu   
Principal Investigator: Kimo Stine, MD         
United States, California
Los Angeles Orthopaedic Hospital - Hemophilia Treatment Center Recruiting
Los Angeles, California, United States, 90007
Contact: Manny Mangilit    213-742-1402    mannymangilit@gmail.com   
Contact: Lucy Lacanilao    213-742-1407    LLacanilao@mednet.ucla.edu   
Principal Investigator: Doris Quon, M.D.         
United States, Idaho
St. Luke's Boise Medical Center Recruiting
Boise, Idaho, United States, 83712
Contact: Tammie Eslinger    208-381-2774    eslinget@slhs.org   
Contact: Tim Honeycutt    208-381-5357    honeycut@slhs.org   
Principal Investigator: Eugenia Chang, M.D.         
United States, Illinois
Rush University Medical Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Kristen Boyce    312-942-0243    kristin_boyce@rush.edu   
Contact: Rosie Howard    312-942-7902    Rosie_Howard@rush.edu   
Principal Investigator: Lisa Boggio, M.D.         
United States, Michigan
Michigan State University Center for Bleeding Disorders & Clotting Disorders Recruiting
East Lansing, Michigan, United States, 48823
Contact: Sue Adkins    517-353-9385    sue.adkins@hc.msu.edu   
Contact: Hillary Witkop    517-353-9385    witkophi@msu.edu   
Principal Investigator: John Penner, M.D.         
United States, Missouri
Children's Mercy Hospital - Kansas City Regional Hemophilia Center Recruiting
Kansas City, Missouri, United States, 64108
Contact: Sara Streeter    816-234-3502    sstreeter@cmh.edu   
Principal Investigator: Brian Wicklund, M.D.         
United States, New York
Long Island Jewish Medical Center - Hemophilia Treatment Center Recruiting
New Hyde Park, New York, United States, 11040
Contact: Patricia Murray    718-470-7380    Pmurray1@nshs.edu   
Contact: Lisa Patriarca    718-470-7380    lpatriar@nshs.edu   
Principal Investigator: Richard Lipton, M.D.         
Canada, Alberta
University of Alberta Recruiting
Edmonton, Alberta, Canada
Contact: Devereux Hannah    +1 780 782 4731    hannah.devereux@biosample.ca   
Principal Investigator: Bruce Ritchie         
Canada, Ontario
McMaster Children's Hospital Recruiting
Hamilton, Ontario, Canada
Contact: Nagel Kim       NAGEL@hhsc.ca   
Principal Investigator: Anthony Chan         
New Zealand
Research Associates, Ltd. Recruiting
Christchurch, New Zealand, 8081
Contact: Carolyn Lauren    +64 3 364 0386    carolyn.lauren@cdhb.health.nz   
Principal Investigator: Mark Smith, M.D.         
Ukraine
Institute of Urgent and Reconstructive surgery named after V.K. Gusak of National Academy of Medical Sciences of Ukraine Recruiting
Donetsk, Ukraine
Principal Investigator: Ekaterina Vilchevska         
Kyiv City Clinical Hospital No 91 Recruiting
Kyiv, Ukraine
Principal Investigator: Ievgenii Averianov         
Institute of Blood Pathology and Transfusion Medicine of National Academy of Medical Sciences of Ukraine Department of Surgery and Clinical Transfusiology Recruiting
Lviv, Ukraine
Principal Investigator: Oleksandra Stasyshyn         
United Kingdom
Royal Cornwall Hospital, Department of Haematology Recruiting
Truro, Cornwall, United Kingdom, TR1 3LJ
Contact: Bianca Mills    01872 252527    bianca.mills@rcht.cornwall.nhs.uk   
Principal Investigator: Desmond Creagh         
Hull Haemophillia Centre, Hull Royal Infirmary Recruiting
Humberside, Hull, United Kingdom, HU3 2JZ HU3 2JZ
Contact: Lisa Armitage    01482 461254    lisa.armitage@hey.nhs.uk   
Principal Investigator: David Allsup, M.D.         
Central Manchester University Hospitals Recruiting
Manchester, Lancashire, United Kingdom
Contact: Foulkes Matt    +44 (0)161 901 4565    Matt.Foulkes@cmft.nhs.uk   
Contact: Davies Carolyn    +44 (0)161 701 4353    clinical.trials@cmft.nhs.uk   
Principal Investigator: Charles Hay         
North Hampshire Haemophilia Centre Recruiting
Basingstoke, North Hampshire, United Kingdom, RG24 9NA
Contact: Yvonne Watson    01256 314793    yvonne.watson@hhft.nhs.uk   
Principal Investigator: Savita Rangarajan         
University of Liverpool Recruiting
Liverpool, United Kingdom, L69 3GA
Contact: Clare Kay-Jones    +44(0)151 706 4329    clare.kay-jones@rlbuht.nhs.uk   
Contact: Jayne Keaney    +44(0)151 706 4329    jayne.keaney@rlbuht.nhs.uk   
Principal Investigator: Tina Dutt, M.D.         
Royal Free Hospital, Haemophilia Centre & Thrombosis Unit Recruiting
London, United Kingdom, NW3 2QG
Principal Investigator: Pratima Chowdary, M.D.         
Churchill Hospital, Oxford Recruiting
Oxford, United Kingdom, OX3 7LE
Contact: Simon Fletcher    +44 1865 225316    Simon.Fletcher@ouh.nhs.uk   
Principal Investigator: Paul Giangrande, M.D.         
Sponsors and Collaborators
Green Cross Corporation
Atlantic Research Group
Investigators
Principal Investigator: Paul LeoFrancis Giangrande, MD Oxford Haemophilic Centre and Thrombosis Unit, Churchill Hospital
  More Information

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: January 2, 2014
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 April 22, 2014