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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Protalix
ClinicalTrials.gov Identifier:
NCT00376168
First received: September 12, 2006
Last updated: July 25, 2012
Last verified: July 2012
  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 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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:


Further study details as provided by Protalix:

Primary Outcome Measures:
  • Change From Baseline in Spleen Volume Measured by MRI. [ Time Frame: Baseline and 9 months ] [ Designated as safety issue: No ]
    Calculated as percent change in spleen volume from Baseline to 9 months


Secondary Outcome Measures:
  • Change From Baseline in Liver Volume [ Time Frame: Baseline and 9 months ] [ Designated as safety issue: No ]
    Calculated as percent change in liver volume from Baseline to 9 months

  • Change in Hemoglobin [ Time Frame: Baseline and Month 9 ] [ Designated as safety issue: No ]
    Absolute change in Hemoglobin concentration from Baseline to Month 9

  • Change in Platelet Count [ Time Frame: Baseline and Month 9 ] [ Designated as safety issue: No ]
    Change in Platelet count from Baseline to Month 9


Other Outcome Measures:
  • Change in Chitotriosidase [ Time Frame: Baseline and Month 9 ] [ Designated as safety issue: No ]
    Change in Chitotriosidase from Baseline to Month 9


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
Experimental: prGCD 30 Units/kg Drug: Plant cell expressed recombinant glucocerebrosidase (prGCD)
Intravenous infusion every two weeks for 9 months
Other Name: Taliglucerase alfa
Experimental: prGCD 60 Units/kg Drug: Plant cell expressed recombinant glucocerebrosidase (prGCD)
Intravenous infusion every 2 weeks for 9 months
Other Name: Taliglucerase alfa

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Rambam Medical Center
Haifa, Israel, 31096
Shaare Zedek Medical Center
Jerusalem, Israel, 91031
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 ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Protalix
ClinicalTrials.gov Identifier: NCT00376168     History of Changes
Other Study ID Numbers: PB-06-001
Study First Received: September 12, 2006
Results First Received: May 11, 2012
Last Updated: July 25, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Gaucher Disease
Sphingolipidoses
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders

ClinicalTrials.gov processed this record on August 18, 2014