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

NCT01619046 | Unknown Phase 3

• 1 other identifier: GreenGeneF_P3
• Study Type: interventional
• Target: 124
• Locations: 7 countries
• Sites: 34

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).

Conditions

Hemophilia A

Keywords

GreenGene™F, Previously Treated Patients

Outcome Measures

Primary Outcomes (1)

• Number of subject with development of inhibitors

  Development of neutralizing antibodies (inhibitors) will be followed during the regular visits, average of 3 months.

  evert 3 months, up to 18 months

Secondary Outcomes (1)

• Describe the PK profile of GreenGene™ F

  Pre-dose, 0~48hours post-dose

Study Arms (4)

PK substudy

ACTIVE COMPARATOR

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

Prophylaxis safety and efficacy substudy

EXPERIMENTAL

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

On-demand safety and efficacy substudy

EXPERIMENTAL

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

Surgical substudy

EXPERIMENTAL

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

Interventions

GreenGene™ F and an approved recombinant Factor VIII product BIOLOGICAL

one 50 IU/kg, intra-venous infusion over 5 minutes, Infusion rate \< 10 mL/min

Also known as: GreenGeneF, GreenGene F

PK substudy

GreenGene™ F BIOLOGICAL

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

Also known as: GreenGeneF, GreenGene F

Prophylaxis safety and efficacy substudy

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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% activity; \<0.01 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 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 (96 h if participating in the PK sub study)
• Absolute CD4 lymphocyte cell count ≥ 200 μL
• Signed the written informed consent form or informed consent was obtained from the subject's legal guardian
• 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
• 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)

You may not qualify if:

• 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 VIII 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 antiretroviral 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

Sponsors & Collaborators

• Green Cross Corporation: lead
• Atlantic Research Group: collaborator

Study Sites (34)

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

RECRUITING

Los Angeles Orthopaedic Hospital - Hemophilia Treatment Center

Los Angeles, California, 90007, United States

RECRUITING

Harbor - UCLA Pediatrics

Torrance, California, 90509, United States

RECRUITING

University of Miami - Comprehensive Hemophilia Center

Miami, Florida, 33101, United States

RECRUITING

St. Luke's Boise Medical Center

Boise, Idaho, 83712, United States

RECRUITING

Rush University Medical Center

Chicago, Illinois, 60612, United States

RECRUITING

Michigan State University Center for Bleeding Disorders & Clotting Disorders

East Lansing, Michigan, 48823, United States

RECRUITING

Children's Mercy Hospital - Kansas City Regional Hemophilia Center

Kansas City, Missouri, 64108, United States

RECRUITING

Long Island Jewish Medical Center - Hemophilia Treatment Center

New Hyde Park, New York, 11040, United States

RECRUITING

Oregon Health and Science University

Portland, Oregon, 97239, United States

RECRUITING

University of Alberta

Edmonton, Alberta, Canada

RECRUITING

McMaster Children's Hospital

Hamilton, Ontario, Canada

RECRUITING

Research Associates, Ltd.

Christchurch, New Zealand, 8081, New Zealand

RECRUITING

Instytut Hematologii i Transfuzjologii

Warsaw, Poland

RECRUITING

wojewodzki szpital Specjalistyczny, klinika hematologii uniwersytetu medycznego w łodzi

Łodzi, Poland

RECRUITING

Barnaul Altai State Scientfic Center

Barnaul, 4656024, Russia

RECRUITING

Kirov Research Institute of Hematology and Blood Transfusion

Kirov, 610027, Russia

RECRUITING

Ismailov City Children's Clinical Hospital of Board of Health of Moscow City

Moscow, 105077, Russia

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

Samara, 443099, Russia

RECRUITING

Ufa Republican Clinical Hospital

Ufa, 450005, Russia

RECRUITING

Dnepropetrovsk City Clinical Hospital

Dnipro, 49102, Ukraine

RECRUITING

Institute of Urgent and Reconstructive surgery named after V.K. Gusak of National Academy of Medical Sciences of Ukraine

Donetsk, Ukraine

RECRUITING

Kharkov Regional Clinical Oncology Center

Kharkiv, 61070, Ukraine

RECRUITING

Kyiv City Clinical Hospital No 91

Kyiv, Ukraine

RECRUITING

Institute of Blood Pathology and Transfusion Medicine of National Academy of Medical Sciences of Ukraine Department of Surgery and Clinical Transfusiology

Lviv, Ukraine

RECRUITING

Zaporizhzhya Region Clinical Child Hospital

Zaporzhye, 69063, Ukraine

RECRUITING

Royal Cornwall Hospital, Department of Haematology

Truro, Cornwall, TR1 3LJ, United Kingdom

RECRUITING

Hull Haemophillia Centre, Hull Royal Infirmary

Humberside, Hull, HU3 2JZ HU3 2JZ, United Kingdom

RECRUITING

Central Manchester University Hospitals

Manchester, Lancashire, United Kingdom

RECRUITING

St. Thomas' Hospital

City of Westminster, London, SE1 7EH, United Kingdom

RECRUITING

North Hampshire Haemophilia Centre

Basingstoke, North Hampshire, RG24 9NA, United Kingdom

RECRUITING

University of Liverpool

Liverpool, L69 3GA, United Kingdom

RECRUITING

Royal Free Hospital, Haemophilia Centre & Thrombosis Unit

London, NW3 2QG, United Kingdom

RECRUITING

Churchill Hospital, Oxford

Oxford, OX3 7LE, United Kingdom

RECRUITING

MeSH Terms

Conditions

Hemophilia A

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Paul LeoFrancis Giangrande, MD

  Oxford Haemophilic Centre and Thrombosis Unit, Churchill Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kevin Wait

CONTACT

540-649-5490; kwait@atlanticresearchgroup.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2012
• First Posted: June 14, 2012
• Study Start: March 1, 2013
• Primary Completion: July 1, 2015
• Study Completion: September 1, 2015
• Last Updated: July 3, 2014

Record last verified: 2014-07

Locations

US (10); PL (2); NZ (1); RU (5); UA (6); CA (2); GB (8)