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

NCT00376168 | Completed Phase 3 Results DMC

• 1 other identifier: PB-06-001
• Study Type: interventional
• Target: 32
• Locations: 8 countries
• Sites: 11

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.

Conditions

Gaucher Disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Change From Baseline in Liver Volume

  Baseline and 9 months

• Change in Hemoglobin

  Baseline and Month 9

• Change in Platelet Count

  Baseline and Month 9

Other Outcomes (1)

• Change in Chitotriosidase

  Baseline and Month 9

Study Arms (2)

prGCD 30 Units/kg

EXPERIMENTAL

Drug: Plant cell expressed recombinant glucocerebrosidase (prGCD)

prGCD 60 Units/kg

EXPERIMENTAL

Drug: Plant cell expressed recombinant glucocerebrosidase (prGCD)

Interventions

Plant cell expressed recombinant glucocerebrosidase (prGCD) DRUG

Intravenous infusion every two weeks for 9 months

Also known as: Taliglucerase alfa

prGCD 30 Units/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (11)

University Research Foundation for Lysosomal Storage Diseases

Coral Springs, Florida, 33065, United States

Location

Division of Medical Genetics, Emory University School of Medicine

Decatur, Georgia, 30033, United States

Location

New York University Medical Center

New York, New York, 10016, United States

Location

Mount Sinai Hospital

Toronto, Ontario, M5G 1X5, Canada

Location

Pontificia Universidad Catolica de Chile

Santiago, Chile

Location

Rambam Medical Center

Haifa, 31096, Israel

Location

Shaare Zedek Medical Center

Jerusalem, 91031, Israel

Location

Universita "La Sapienza"

Rome, 00161, Italy

Location

Morningside Medi-Clinic

Morningside, 2196, South Africa

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 26053270 DERIVED

• 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.

  PMID: 21900191 DERIVED

• 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.

  PMID: 18729283 DERIVED

MeSH Terms

Conditions

Gaucher Disease

Interventions

taliglucerase alfa

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Results Point of Contact

• Title: Einat Almon
• Organization: Protalix Ltd.

einata@protalix.com

972-4-9889488

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2006
• First Posted: September 14, 2006
• Study Start: August 1, 2007
• Primary Completion: September 1, 2009
• Study Completion: October 1, 2009
• Last Updated: October 4, 2018
• Results First Posted: July 26, 2012

Record last verified: 2018-09

Locations

US (3); CL (1); ZA (1); IL (2); ES (1); IT (1); CA (1); GB (1)