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

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

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.

Study Overview

• Status: Completed
• Conditions: Gaucher Disease
• Intervention / Treatment: Drug: Plant cell expressed recombinant glucocerebrosidase (prGCD); Drug: Plant cell expressed recombinant glucocerebrosidase (prGCD)

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 Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital
• Chile
  • Santiago, Chile
    • Pontificia Universidad Catolica de Chile
• Israel
  • Haifa, Israel, 31096
    • Rambam Medical Center
  • Jerusalem, Israel, 91031
    • Shaare Zedek Medical Center
• Italy
  • Rome, Italy, 00161
    • Università "La Sapienza"
• South Africa
  • Morningside, South Africa, 2196
    • Morningside Medi-Clinic
• Spain
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
• United Kingdom
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital
• United States
  • Florida
    • Coral Springs, Florida, United States, 33065
      • University Research Foundation for Lysosomal Storage Diseases
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Division of Medical Genetics, Emory University School of Medicine
  • New York
    • New York, New York, United States, 10016
      • New York University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: prGCD 30 Units/kg	Drug: Plant cell expressed recombinant glucocerebrosidase (prGCD); Intravenous infusion every two weeks for 9 months; Other Names: Taliglucerase alfa; Drug: Plant cell expressed recombinant glucocerebrosidase (prGCD); Intravenous infusion every 2 weeks for 9 months; Other Names: Taliglucerase alfa
Experimental: prGCD 60 Units/kg	Drug: Plant cell expressed recombinant glucocerebrosidase (prGCD); Intravenous infusion every two weeks for 9 months; Other Names: Taliglucerase alfa; Drug: Plant cell expressed recombinant glucocerebrosidase (prGCD); Intravenous infusion every 2 weeks for 9 months; Other Names: Taliglucerase alfa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Chitotriosidase	Change in Chitotriosidase from Baseline to Month 9	Baseline and Month 9

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• 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, Munoz 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. No abstract available. German.

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: September 12, 2006
• First Submitted That Met QC Criteria: September 12, 2006
• First Posted (Estimate): September 14, 2006

Study Record Updates

• Last Update Posted (Actual): October 4, 2018
• Last Update Submitted That Met QC Criteria: September 5, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Lipidoses; Lipid Metabolism, Inborn Errors; Gaucher Disease
• Other Study ID Numbers: PB-06-001