Clinical trial NCT00376168: A Phase III Trial to Assess the Safety and Efficacy of Plant Cell Expressed GCD in Patients With Gaucher Disease
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gaucher Disease
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2006-09-14
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Change From Baseline in Spleen Volume Measured by MRI.
timeFrame: Baseline and 9 months
Secondary outcomes:
measure: Change From Baseline in Liver Volume
timeFrame: Baseline and 9 months
measure: Change in Hemoglobin
timeFrame: Baseline and Month 9
measure: Change in Platelet Count
timeFrame: Baseline and Month 9
Other outcomes:
measure: Change in Chitotriosidase
timeFrame: Baseline and Month 9
Locations:
city: Coral Springs
country: United States
facility: University Research Foundation for Lysosomal Storage Diseases
state: Florida
city: Decatur
country: United States
facility: Division of Medical Genetics, Emory University School of Medicine
state: Georgia
city: New York
country: United States
facility: New York University Medical Center
state: New York
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Santiago
country: Chile
facility: Pontificia Universidad Catolica de Chile
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Rome
country: Italy
facility: Universita "La Sapienza"
city: Morningside
country: South Africa
facility: Morningside Medi-Clinic
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: London
country: United Kingdom
facility: Royal Free Hospital
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.