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

Phase 3

Completed

Interventions: Drug: Plant cell expressed recombinant glucocerebrosidase (prGCD)

Brief Summary: 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.

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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
prGCD 60 Units/kg	Plant cell expressed recombinant glucocerebrosidase (prGCD)	-
prGCD 30 Units/kg	Plant cell expressed recombinant glucocerebrosidase (prGCD)	-

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Spleen Volume Measured by MRI.	Baseline and 9 months	Calculated as percent change in spleen volume from Baseline to 9 months

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Liver Volume	Baseline and 9 months	Calculated as percent change in liver volume from Baseline to 9 months
Change in Hemoglobin	Baseline and Month 9	Absolute change in Hemoglobin concentration from Baseline to Month 9
Change in Platelet Count	Baseline and Month 9	Change in Platelet count from Baseline to Month 9

Locations (11): Hospital Universitario Miguel Servet
🇪🇸
Zaragoza, Spain
Shaare Zedek Medical Center
🇮🇱
Jerusalem, Israel
Rambam Medical Center
🇮🇱
Haifa, Israel
New York University Medical Center
🇺🇸
New York, New York, United States
Mount Sinai Hospital
🇨🇦
Toronto, Ontario, Canada
University Research Foundation for Lysosomal Storage Diseases
🇺🇸
Coral Springs, Florida, United States
Division of Medical Genetics, Emory University School of Medicine
🇺🇸
Decatur, Georgia, United States
Pontificia Universidad Catolica de Chile
🇨🇱
Santiago, Chile
Universita "La Sapienza"
🇮🇹
Rome, Italy
Morningside Medi-Clinic
🇿🇦
Morningside, South Africa
Royal Free Hospital
🇬🇧
London, United Kingdom