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

NCT ID: NCT01619046

Last Updated: 2014-07-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

124 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-03-31

Study Completion Date

2015-09-30

Brief Summary

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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).

Detailed Description

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Conditions

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Hemophilia A

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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).

Group Type ACTIVE_COMPARATOR

GreenGene™ F and an approved recombinant Factor VIII product

Intervention Type BIOLOGICAL

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

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.

Group Type EXPERIMENTAL

GreenGene™ F

Intervention Type 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

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.

Group Type EXPERIMENTAL

GreenGene™ F

Intervention Type BIOLOGICAL

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

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

Group Type EXPERIMENTAL

GreenGene™ F

Intervention Type BIOLOGICAL

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.

Interventions

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GreenGene™ F and an approved recombinant Factor VIII product

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

Intervention Type 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

Intervention Type 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

Intervention Type 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.

Intervention Type BIOLOGICAL

Other Intervention Names

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GreenGeneF GreenGene F GreenGeneF GreenGene F GreenGeneF GreenGene F GreenGeneF GreenGene F

Eligibility Criteria

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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
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Atlantic Research Group

OTHER

Sponsor Role collaborator

Green Cross Corporation

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Paul LeoFrancis Giangrande, MD

Role: PRINCIPAL_INVESTIGATOR

Oxford Haemophilic Centre and Thrombosis Unit, Churchill Hospital

Locations

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Arkansas Children's Hospital

Little Rock, Arkansas, United States

Site Status RECRUITING

Los Angeles Orthopaedic Hospital - Hemophilia Treatment Center

Los Angeles, California, United States

Site Status RECRUITING

Harbor - UCLA Pediatrics

Torrance, California, United States

Site Status RECRUITING

University of Miami - Comprehensive Hemophilia Center

Miami, Florida, United States

Site Status RECRUITING

St. Luke's Boise Medical Center

Boise, Idaho, United States

Site Status RECRUITING

Rush University Medical Center

Chicago, Illinois, United States

Site Status RECRUITING

Michigan State University Center for Bleeding Disorders & Clotting Disorders

East Lansing, Michigan, United States

Site Status RECRUITING

Children's Mercy Hospital - Kansas City Regional Hemophilia Center

Kansas City, Missouri, United States

Site Status RECRUITING

Long Island Jewish Medical Center - Hemophilia Treatment Center

New Hyde Park, New York, United States

Site Status RECRUITING

Oregon Health and Science University

Portland, Oregon, United States

Site Status RECRUITING

University of Alberta

Edmonton, Alberta, Canada

Site Status RECRUITING

McMaster Children's Hospital

Hamilton, Ontario, Canada

Site Status RECRUITING

Research Associates, Ltd.

Christchurch, New Zealand, New Zealand

Site Status RECRUITING

Instytut Hematologii i Transfuzjologii

Warsaw, , Poland

Site Status RECRUITING

wojewodzki szpital Specjalistyczny, klinika hematologii uniwersytetu medycznego w łodzi

Łodzi, , Poland

Site Status RECRUITING

Barnaul Altai State Scientfic Center

Barnaul, , Russia

Site Status RECRUITING

Kirov Research Institute of Hematology and Blood Transfusion

Kirov, , Russia

Site Status RECRUITING

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

Moscow, , Russia

Site Status 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, , Russia

Site Status RECRUITING

Ufa Republican Clinical Hospital

Ufa, , Russia

Site Status RECRUITING

Dnepropetrovsk City Clinical Hospital

Dnipro, , Ukraine

Site Status RECRUITING

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

Donetsk, , Ukraine

Site Status RECRUITING

Kharkov Regional Clinical Oncology Center

Kharkiv, , Ukraine

Site Status RECRUITING

Kyiv City Clinical Hospital No 91

Kyiv, , Ukraine

Site Status RECRUITING

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

Lviv, , Ukraine

Site Status RECRUITING

Zaporizhzhya Region Clinical Child Hospital

Zaporzhye, , Ukraine

Site Status RECRUITING

Royal Cornwall Hospital, Department of Haematology

Truro, Cornwall, United Kingdom

Site Status RECRUITING

Hull Haemophillia Centre, Hull Royal Infirmary

Humberside, Hull, United Kingdom

Site Status RECRUITING

Central Manchester University Hospitals

Manchester, Lancashire, United Kingdom

Site Status RECRUITING

St. Thomas' Hospital

City of Westminster, London, United Kingdom

Site Status RECRUITING

North Hampshire Haemophilia Centre

Basingstoke, North Hampshire, United Kingdom

Site Status RECRUITING

University of Liverpool

Liverpool, , United Kingdom

Site Status RECRUITING

Royal Free Hospital, Haemophilia Centre & Thrombosis Unit

London, , United Kingdom

Site Status RECRUITING

Churchill Hospital, Oxford

Oxford, , United Kingdom

Site Status RECRUITING

Countries

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United States Canada New Zealand Poland Russia Ukraine United Kingdom

Central Contacts

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Kevin Wait

Role: CONTACT

540-649-5490

Facility Contacts

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Bryce Warren

Role: primary

Manny Mangilit

Role: primary

213-742-1402

Lucy Lacanilao

Role: backup

213-742-1407

Amy Warder

Role: primary

310-222-3621

Helen Todoroki

Role: backup

310-222-4156

Clara Ibarra

Role: primary

305-243-5343

Cecilia Prado

Role: backup

305-243-6925

Tammie Eslinger

Role: primary

208-381-2774

Tim Honeycutt

Role: backup

208-381-5357

Kristen Boyce

Role: primary

312-942-0243

Rosie Howard

Role: backup

312-942-7902

Sue Adkins

Role: primary

517-353-9385

Hillary Witkop

Role: backup

517-353-9385

Sara Streeter

Role: primary

816-234-3502

Patricia Murray

Role: primary

718-470-7380

Lisa Patriarca

Role: backup

718-470-7380

Kathy Beach

Role: primary

503-494-7425

Alysia Cox

Role: backup

503-494-5109

Devereux Hannah

Role: primary

+1 780 782 4731

Nagel Kim

Role: primary

Carolyn Lauren

Role: primary

+64 3 364 0386

Bianca Mills

Role: primary

01872 252527

Lisa Armitage

Role: primary

01482 461254

Foulkes Matt

Role: primary

+44 (0)161 901 4565

Davies Carolyn

Role: backup

+44 (0)161 701 4353

Elsa Aradom

Role: primary

020-7188-2781

Sheela Medahunsi

Role: backup

020-7188-2808

Yvonne Watson

Role: primary

01256 314793

Clare Kay-Jones

Role: primary

+44(0)151 706 4329

Jayne Keaney

Role: backup

+44(0)151 706 4329

Simon Fletcher

Role: primary

+44 1865 225316

Other Identifiers

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GreenGeneF_P3

Identifier Type: -

Identifier Source: org_study_id

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