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

Gaucher Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00376168
• Other study ID #: PB-06-001
• Status: Completed
• Phase: Phase 3
• Start date: August 2007
• Est. completion date: October 2009

Study information

• Verified date: September 2018
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: October 2009
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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.

Related Conditions & MeSH terms

• Gaucher Disease

Intervention

Drug:
• Plant cell expressed recombinant glucocerebrosidase (prGCD)
Intravenous infusion every two weeks for 9 months
• Plant cell expressed recombinant glucocerebrosidase (prGCD)
Intravenous infusion every 2 weeks for 9 months

Locations

Country	Name	City	State
Canada	Mount Sinai Hospital	Toronto	Ontario
Chile	Pontificia Universidad Catolica de Chile	Santiago
Israel	Rambam Medical Center	Haifa
Israel	Shaare Zedek Medical Center	Jerusalem
Italy	Universita "La Sapienza"	Rome
South Africa	Morningside Medi-Clinic	Morningside
Spain	Hospital Universitario Miguel Servet	Zaragoza
United Kingdom	Royal Free Hospital	London
United States	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	New York University Medical Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Canada,  Chile,  Israel,  Italy,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Chitotriosidase	Change in Chitotriosidase from Baseline to Month 9	Baseline and Month 9
Primary	Change From Baseline in Spleen Volume Measured by MRI.	Calculated as percent change in spleen volume from Baseline to 9 months	Baseline and 9 months
Secondary	Change From Baseline in Liver Volume	Calculated as percent change in liver volume from Baseline to 9 months	Baseline and 9 months
Secondary	Change in Hemoglobin	Absolute change in Hemoglobin concentration from Baseline to Month 9	Baseline and Month 9
Secondary	Change in Platelet Count	Change in Platelet count from Baseline to Month 9	Baseline and Month 9