A Phase III Trial to Assess the Safety and Efficacy of Plant Cell Expressed GCD in Patients With Gaucher Disease - Full Text View

Sponsor:	Protalix
Information provided by:	Protalix
ClinicalTrials.gov Identifier:	NCT00376168

Purpose

Gaucher disease, the most prevalent lysosomal storage disorder, is caused by mutations in the human glucocerebrosidase gene (GCD) leading to reduced activity of the lysosomal enzyme glucocerebrosidase and thereby to the accumulation of substrate glucocerebroside (GlcCer) in the cells of the monocyte-macrophage system.

This is the second trial to utilize a recombinant active form of lysosomal enzyme, glucocerebrosidase, (human prGCD) which is expressed and purified in a bioreactor system from transformed carrot plant root cell line.

Condition	Intervention	Phase
Gaucher Disease	Drug: Plant cell expressed recombinant glucocerebrosidase (prGCD)	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Dose Comparison, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Phase III, Multicenter, Randomized, Double-Blind Trial to Assess the Safety and Efficacy of Two Parallel Dose Groups of Plant Cell Expressed Recombinant Human Glucocerebrosidase (prGCD) in Patients With Gaucher Disease

Resource links provided by NLM:

Genetics Home Reference related topics: Chanarin-Dorfman syndrome cholesteryl ester storage disease Farber lipogranulomatosis Gaucher disease primary carnitine deficiency succinic semialdehyde dehydrogenase deficiency

MedlinePlus related topics: Gaucher's Disease

Drug Information available for: Alglucerase Imiglucerase

U.S. FDA Resources

Further study details as provided by Protalix:

Primary Outcome Measures:

Change from baseline in spleen volume measured by MRI. [ Time Frame: 9 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change from baseline in: Liver volume, Hemoglobin measurement, Platelet count, Biomarkers (chitotriosidase and pulmonary and activation-regulated chemokine (PARC/ CCL18) [ Time Frame: 9 months ] [ Designated as safety issue: No ]

Enrollment:	32
Study Start Date:	August 2007
Study Completion Date:	October 2009
Primary Completion Date:	September 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
prGCD 30 Units/kg: Experimental	Drug: Plant cell expressed recombinant glucocerebrosidase (prGCD) Intravenous infusion every two weeks for 9 months
prGCD 60 Units/kg: Experimental	Drug: Plant cell expressed recombinant glucocerebrosidase (prGCD) Intravenous infusion every 2 weeks for 9 months

Detailed Description:

This will be a multi-center, randomized, double-blind, parallel group, dose-ranging trial to assess the safety and efficacy of prGCD in 30 untreated patients with Gaucher disease. Patients will receive IV infusion of prGCD every two weeks at the selected medical center. The duration of the study will be nine months. At the end of the 9-month treatment period (20 visits, 38 weeks) eligible patients will be offered enrollment in an open-label extension study.

There will be two treatment groups, 15 patients in each treatment group.

Treatment Group I: 30 units/kg every 2 weeks. Treatment Group II: 60 units/kg every 2 weeks.

All patients will have pharmacokinetic data collected over approximately 3 hours with frequent blood samples following the first and final doses of prGCD.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Males and females, 18 years or older
Confirmed enzymatic diagnosis of Gaucher disease
Splenomegaly defined as greater than eight times the expected volume (measured volume divided by estimated volume (0.2% of body weight)] as determined by MRI volumetric analysis
Female patients of child-bearing potential who agree to use a medically acceptable method of contraception
Thrombocytopenia (defined as platelet counts below the lower limit of normal) and/or anemia (defined by hemoglobin level at least 1 g/dL below normal range according to sex and age).
Patients who have not received ERT in the past or patients whoc have not received ERT in the past 12 months and have a negative anti-glucocerebrosidase antibody test.
Patients who have not received substrate reduction therapy (SRT) in the past 12 months.
Ability to provide a written informed consent.

Exclusion Criteria:

Currently taking another experimental drug for any condition
Pregnant or nursing
Presence of HIV and/or, HBsAg and/or hepatitis C infections
Presence of severe neurological signs and symptoms, defined as complete ocular paralysis, overt myoclonus or history of seizures, characteristic of neuronopathic Gaucher disease.
Previous anaphylactoid reaction to Cerezyme® or Ceredase®.
History of allergy to carrots.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00376168

Locations

United States, Florida
University Research Foundation for Lysosomal Storage Diseases
Coral Springs, Florida, United States, 33065
United States, Georgia
Division of Medical Genetics, Emory University School of Medicine
Decatur, Georgia, United States, 30033
United States, New York
New York University Medical Center
New York, New York, United States, 10016
Canada, Ontario
Mount Sinai Hospital
Toronto, Ontario, Canada, M5G 1X5
Chile
Pontificia Universidad Catolica de Chile
Santiago, Chile
Israel
Shaare Zedek Medical Center
Jerusalem, Israel, 91031
Rambam Medical Center
Haifa, Israel, 31096
Italy
Universita "La Sapienza"
Rome, Italy, 00161
South Africa
Morningside Medi-Clinic
Morningside, South Africa, 2196
Spain
Hospital Universitario Miguel Servet
Zaragoza, Spain, 50009
United Kingdom
Royal Free Hospital
London, United Kingdom, NW3 2QG

Sponsors and Collaborators

Protalix

Investigators

Principal Investigator:

Ari Zimran, MD

Shaare Zedek Medical Center, Jerusalem, Israel

More Information

No publications provided by Protalix

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

Winckler T. [In Process Citation] Pharm Unserer Zeit. 2008;37(5):352-3. German. No abstract available.

Responsible Party:	Protalix ( Einat Almon )
Study ID Numbers:	PB-06-001
Study First Received:	September 12, 2006
Last Updated:	October 6, 2009
ClinicalTrials.gov Identifier:	NCT00376168 History of Changes
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Lipid Metabolism, Inborn Errors
Sphingolipidoses
Metabolic Diseases
Reticuloendotheliosis
Lysosomal Storage Diseases, Nervous System
Lysosomal Storage Diseases
Nervous System Diseases
Central Nervous System Diseases
Brain Diseases

Lymphatic Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Brain Diseases, Metabolic, Inborn
Lipidoses
Gaucher Disease
Lipid Metabolism Disorders
Brain Diseases, Metabolic

ClinicalTrials.gov processed this record on February 08, 2010