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

• ClinicalTrials.gov Identifier: NCT00376168
• Recruitment Status: Completed
• First Posted: September 14, 2006
• Results First Posted: July 26, 2012
• Last Update Posted: October 4, 2018
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Gaucher Disease	Drug: Plant cell expressed recombinant glucocerebrosidase (prGCD)	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, 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
• Study Start Date: August 2007
• Actual Primary Completion Date: September 2009
• Actual Study Completion Date: October 2009

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Spleen Volume Measured by MRI. [ Time Frame: Baseline and 9 months ]
   Calculated as percent change in spleen volume from Baseline to 9 months

Secondary Outcome Measures :

1. Change From Baseline in Liver Volume [ Time Frame: Baseline and 9 months ]
   Calculated as percent change in liver volume from Baseline to 9 months
2. Change in Hemoglobin [ Time Frame: Baseline and Month 9 ]
   Absolute change in Hemoglobin concentration from Baseline to Month 9
3. Change in Platelet Count [ Time Frame: Baseline and Month 9 ]
   Change in Platelet count from Baseline to Month 9

Other Outcome Measures:

1. Change in Chitotriosidase [ Time Frame: Baseline and Month 9 ]
   Change in Chitotriosidase from Baseline to Month 9

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

Pfizer

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Abbas R, Park G, Damle B, Chertkoff R, Alon S. Pharmacokinetics of Novel Plant Cell-Expressed Taliglucerase Alfa in Adult and Pediatric Patients with Gaucher Disease. PLoS One. 2015 Jun 8;10(6):e0128986. doi: 10.1371/journal.pone.0128986. eCollection 2015.

Zimran A, Brill-Almon E, Chertkoff R, Petakov M, Blanco-Favela F, Muñoz ET, Solorio-Meza SE, Amato D, Duran G, Giona F, Heitner R, Rosenbaum H, Giraldo P, Mehta A, Park G, Phillips M, Elstein D, Altarescu G, Szleifer M, Hashmueli S, Aviezer D. Pivotal trial with plant cell-expressed recombinant glucocerebrosidase, taliglucerase alfa, a novel enzyme replacement therapy for Gaucher disease. Blood. 2011 Nov 24;118(22):5767-73. doi: 10.1182/blood-2011-07-366955. Epub 2011 Sep 6. Erratum in: Blood. 2012 May 10;119(19):4577.

Winckler T. [Enzyme replacement therapy for Gaucher's Disease]. Pharm Unserer Zeit. 2008;37(5):352-3. doi: 10.1002/pauz.200890067. German.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00376168
• Other Study ID Numbers: PB-06-001
• First Posted: September 14, 2006
• Results First Posted: July 26, 2012
• Last Update Posted: October 4, 2018
• Last Verified: September 2018

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