Clinical trial NCT00962260: Expanded Access Trial of Plant Expressed Recombinant Glucocerebrosidase (prGCD) in Patients With Gaucher Disease
Official title: An Open-label Expanded Access Trial of Plant Cell Expressed Recombinant Human Glucocerebrosidase (prGCD) in Patients With Gaucher Disease Who Require Enzyme Replacement Therapy
Study type: EXPANDED_ACCESS
Overall status: NO_LONGER_AVAILABLE
Conditions: Gaucher Disease
Keywords: glucocerebrosidase
enzyme replacement therapy
Gaucher disease
plant cell culture
splenomegaly
hepatomegaly
anemia
thrombocytopenia
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2009-08-19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT

Brief summary: This is an open-label expanded access trial of prGCD in patients with Gaucher disease who require enzyme replacement therapy (ERT) and who have been treated with imiglucerase but for whom the dose has been reduced or discontinued due to shortage of the product.

Detailed description: Gaucher disease, the most prevalent lysosomal storage disorder, is caused by mutations in the human glucocerebrosidase gene (GCD), which have been mapped to chromosome 1 q21-q31, 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 accumulation leads to the visceral manifestations of hepatosplenomegaly, anemia and thrombocytopenia, as well as to the skeletal features and less frequently also to lung involvement.

prGCD is a plant cell expressed recombinant glucocerebrosidase enzyme for the treatment of Gaucher disease. Expression of proteins in plant cell culture is highly efficient, does not require post-expression modification of the protein, and is not susceptible to contamination by agents such as viruses that are pathological to humans.

prGCD safety will be observed in this treatment protocol of patients with non-neuronopathic Gaucher disease who require enzyme replacement therapy. Eligible patients will receive intravenous (IV) infusions of prGCD every two weeks. The dose of prGCD will be equal to each patient's previous imiglucerase dose before reduction or discontinuation due to shortage. The infusions will be administered at the selected medical center.

Eligibility criteria: Inclusion Criteria:

* Males and females, 18 years or older
* Diagnosis of Gaucher disease treated historically with imiglucerase
* Able to provide written informed consent

Exclusion Criteria:

* Currently taking another experimental drug for any condition
* History of allergy to carrots
* Previous infusion reaction suspected to be allergic in nature to Cerezyme® or Ceredase® or receiving premedication to prevent infusion reactions
* Allergy to beta-lactam antibiotics
* Presence of any medical, emotional, behavioral or psychological condition that in the judgment of the Investigator would interfere with the patient's compliance with the requirements of the study.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: La Jolla Village Family Medical Group
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Coral Springs
country: United States
facility: University Research Foundation for Lysosomal Storage Diseases, Inc.
state: Florida
city: Decatur
country: United States
facility: Department of Human Genetics, Emory University School of Medicine
state: Georgia
city: Skokie
country: United States
facility: Orchard Healthcare Research Inc.
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: New York
country: United States
facility: Neurogenetics, NYU at Rivergate
state: New York
city: Durham
country: United States
facility: Division of Medical Genetics, Duke University Medical Center
state: North Carolina
city: Pittsburgh
country: United States
facility: Department of Medical Genetics, Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Dallas
country: United States
facility: Baylor University Medical Center at Dallas, Institute of Metabolic Disease
state: Texas
city: Springfield
country: United States
facility: Center for Clinical Trials
state: Virginia
city: Seattle
country: United States
facility: University of Washington, Department of Pediatrics
state: Washington
city: Jerusalem
country: Israel
facility: Sha'are Zedek Medical Center
Study officials:
References:
citation: Shaaltiel Y, Bartfeld D, Hashmueli S, Baum G, Brill-Almon E, Galili G, Dym O, Boldin-Adamsky SA, Silman I, Sussman JL, Futerman AH, Aviezer D. Production of glucocerebrosidase with terminal mannose glycans for enzyme replacement therapy of Gaucher's disease using a plant cell system. Plant Biotechnol J. 2007 Sep;5(5):579-90. doi: 10.1111/j.1467-7652.2007.00263.x. Epub 2007 May 24.
citation: Aviezer D, Brill-Almon E, Shaaltiel Y, Hashmueli S, Bartfeld D, Mizrachi S, Liberman Y, Freeman A, Zimran A, Galun E. A plant-derived recombinant human glucocerebrosidase enzyme--a preclinical and phase I investigation. PLoS One. 2009;4(3):e4792. doi: 10.1371/journal.pone.0004792. Epub 2009 Mar 11.