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

July 2, 2014 updated by: Green Cross Corporation

Determination of Safety, Efficacy and Pharmacokinetics of GreenGene™ F in Previously Treated Patients 12 Years of Age or Older Diagnosed With Severe Hemophilia A

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 Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

124

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada
        • Recruiting
        • University of Alberta
        • Contact:
        • Principal Investigator:
          • Bruce Ritchie
    • Ontario
      • Hamilton, Ontario, Canada
        • Recruiting
        • McMaster Children's Hospital
        • Contact:
        • Principal Investigator:
          • Anthony Chan
  • New Zealand
      • Christchurch, New Zealand, 8081
        • Recruiting
        • Research Associates, Ltd.
        • Contact:
        • Principal Investigator:
          • Mark Smith, M.D.
  • Poland
      • Warszawa, Poland
        • Recruiting
        • Instytut Hematologii i Transfuzjologii
        • Principal Investigator:
          • Marcin Pasiarski, M.D.
      • Łodzi, Poland
        • Recruiting
        • wojewodzki szpital Specjalistyczny, klinika hematologii uniwersytetu medycznego w łodzi
        • Principal Investigator:
          • Krzysztof Chojnowski, M.D.
  • Russian Federation
      • Barnaul, Russian Federation, 4656024
        • Recruiting
        • Barnaul Altai State Scientfic Center
        • Principal Investigator:
          • A Mamaev, M.D.
      • Kirov, Russian Federation, 610027
        • Recruiting
        • Kirov Research Institute of Hematology and Blood Transfusion
        • Principal Investigator:
          • M Timofeeva, M.D.
      • Moscow, Russian Federation, 105077
        • Recruiting
        • Ismailov City Children's Clinical Hospital of Board of Health of Moscow City
        • Principal Investigator:
          • Vladimir Vdovin, M.D.
      • Samara, Russian Federation, 443099
        • Recruiting
        • State Budget Educational Institution of Higher professional Education "Samara State Medical University" of the Ministry of Health and Social Process of the Russian Federation
        • Principal Investigator:
          • Igor Davydkin, M.D.
      • Ufa, Russian Federation, 450005
        • Recruiting
        • Ufa Republican Clinical Hospital
        • Principal Investigator:
          • G Gaysarova, M.D.
  • Ukraine
      • Dnepropetrovsk, Ukraine, 49102
        • Recruiting
        • Dnepropetrovsk City Clinical Hospital
        • Principal Investigator:
          • Y Shinkarenko, M.D.
      • Donetsk, Ukraine
        • Recruiting
        • Institute of Urgent and Reconstructive surgery named after V.K. Gusak of National Academy of Medical Sciences of Ukraine
        • Principal Investigator:
          • Ekaterina Vilchevska
      • Kharkov, Ukraine, 61070
        • Recruiting
        • Kharkov Regional Clinical Oncology Center
        • Principal Investigator:
          • Tetyana Poposvka, M.D.
      • Kyiv, Ukraine
        • Recruiting
        • Kyiv City Clinical Hospital No 91
        • Principal Investigator:
          • Ievgenii Averianov
      • Lviv, Ukraine
        • Recruiting
        • Institute of Blood Pathology and Transfusion Medicine of National Academy of Medical Sciences of Ukraine Department of Surgery and Clinical Transfusiology
        • Principal Investigator:
          • Oleksandra Stasyshyn
      • Zaporzhye, Ukraine, 69063
        • Recruiting
        • Zaporizhzhya Region Clinical Child Hospital
        • Principal Investigator:
          • A Borodin, M.D.
  • United Kingdom
      • Liverpool, United Kingdom, L69 3GA
      • London, United Kingdom, NW3 2QG
        • Recruiting
        • Royal Free Hospital, Haemophilia Centre & Thrombosis Unit
        • Principal Investigator:
          • Pratima Chowdary, M.D.
      • Oxford, United Kingdom, OX3 7LE
        • Recruiting
        • Churchill Hospital, Oxford
        • Contact:
        • Principal Investigator:
          • Paul Giangrande, M.D.
    • Cornwall
      • Truro, Cornwall, United Kingdom, TR1 3LJ
        • Recruiting
        • Royal Cornwall Hospital, Department of Haematology
        • Contact:
        • Principal Investigator:
          • Desmond Creagh
    • Hull
      • Humberside, Hull, United Kingdom, HU3 2JZ HU3 2JZ
        • Recruiting
        • Hull Haemophillia Centre, Hull Royal Infirmary
        • Contact:
        • Principal Investigator:
          • David Allsup, M.D.
    • Lancashire
      • Manchester, Lancashire, United Kingdom
        • Recruiting
        • Central Manchester University Hospitals
        • Contact:
        • Contact:
        • Principal Investigator:
          • Charles Hay
    • London
      • Westminster, London, United Kingdom, SE1 7EH
    • North Hampshire
      • Basingstoke, North Hampshire, United Kingdom, RG24 9NA
        • Recruiting
        • North Hampshire Haemophilia Centre
        • Contact:
        • Principal Investigator:
          • Savita Rangarajan
  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72202
    • California
      • Los Angeles, California, United States, 90007
        • Recruiting
        • Los Angeles Orthopaedic Hospital - Hemophilia Treatment Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Doris Quon, M.D.
      • Torrance, California, United States, 90509
        • Recruiting
        • Harbor - UCLA Pediatrics
        • Contact:
        • Contact:
        • Principal Investigator:
          • Joseph Lasky, M.D.
    • Florida
      • Miami, Florida, United States, 33101
        • Recruiting
        • University of Miami - Comprehensive Hemophilia Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Joanna Davis, M.D.
    • Idaho
      • Boise, Idaho, United States, 83712
        • Recruiting
        • St. Luke's Boise Medical Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Eugenia Chang, M.D.
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Recruiting
        • Rush University Medical Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Lisa Boggio, M.D.
    • Michigan
      • East Lansing, Michigan, United States, 48823
        • Recruiting
        • Michigan State University Center for Bleeding Disorders & Clotting Disorders
        • Contact:
        • Contact:
        • Principal Investigator:
          • John Penner, M.D.
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Recruiting
        • Children's Mercy Hospital - Kansas City Regional Hemophilia Center
        • Contact:
        • Principal Investigator:
          • Brian Wicklund, M.D.
    • New York
      • New Hyde Park, New York, United States, 11040
        • Recruiting
        • Long Island Jewish Medical Center - Hemophilia Treatment Center
        • Contact:
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Oregon Health and Science University
        • Contact:
        • Contact:
        • Principal Investigator:
          • Michael Recht, M.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
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
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
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, 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
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
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
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, 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
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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of subject with development of inhibitors
Time Frame: evert 3 months, up to 18 months
Development of neutralizing antibodies (inhibitors) will be followed during the regular visits, average of 3 months.
evert 3 months, up to 18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Describe the PK profile of GreenGene™ F
Time Frame: Pre-dose, 0~48hours post-dose
AUC, AUMC, Half-life, Incremental recovery, Mean residence time (MRT), Clearance, Volume of distribution - steady state, Cmax, Tmax
Pre-dose, 0~48hours post-dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Green Cross Corporation

Collaborators

Atlantic Research Group

Investigators

  • Principal Investigator: Paul LeoFrancis Giangrande, MD, Oxford Haemophilic Centre and Thrombosis Unit, Churchill Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2013

Primary Completion (ANTICIPATED)

July 1, 2015

Study Completion (ANTICIPATED)

September 1, 2015

Study Registration Dates

First Submitted

May 31, 2012

First Submitted That Met QC Criteria

June 12, 2012

First Posted (ESTIMATE)

June 14, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

July 3, 2014

Last Update Submitted That Met QC Criteria

July 2, 2014

Last Verified

July 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GreenGeneF_P3

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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