Phase I Single Dose-Escalation Safety Study of Human Glucocerebrosidase (prGCD)

A Phase I, Non-Randomized, Open Label, Single Dose-Escalation Safety Study of Recombinant Human Glucocerebrosidase (prGCD) in Healthy Volunteers

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 first 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: Human Glucocerebrosidase (prGCD)

• Study Type: Interventional
• Enrollment: 6
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy male or female between 18 and 45 years of age.
2. Female subjects must agree to use a medically acceptable method of contraception at all times during the study and must have a negative serum pregnancy test at baseline and during the study period.
3. Females of child-bearing potential must be non-pregnant and not lactating and using adequate birth control such as oral contraceptives.
4. Negative laboratory tests for HIV, HBsAg or HCV.
5. Naive to any previous recombinant protein therapy.
6. Provide written informed consent.
7. Have the ability to understand the requirements of the study and to comply with the study protocol and dosing regimen.

Exclusion Criteria:

1. Have clinical evidence of any active significant disease that could potentially compromise the ability of the investigator to evaluate or interpret the effects of the study treatment on safety assessment and thus increase the risk to the subject to unacceptable levels.
2. Are pregnant or nursing.
3. Presence of any acute or chronic diseases.
4. Have a history of any allergies.
5. Have been exposed to long-term steroid treatment.
6. Had a minor operation in the last 6 months.
7. Have ever been exposed to any previous recombinant protein therapy.
8. Have received immuno-suppressive treatment.
9. Have a positive HIV, HBsAG and HCV laboratory result.
10. Use any medication other than vitamins or oral contraceptives (for female).
11. Have participated in another clinical trial during the previous 3 months
12. Have history of alcohol or drug abuse.
13. Are considered by the Investigator to be unsuitable candidate for this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
adverse events
physical examination
Safety as measured by:
change in vital signs
laboratory test results

Secondary Outcome Measures

Outcome Measure
Pharmacokinetic parameters
Immunological profile including: IgE, anti human prGCD antibodies, eosinophils and proteinuria

Collaborators and Investigators

• Sponsor: Protalix
• Investigators: Principal Investigator: Eithan Galun, MD, Protalix Ltd.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2005
• Study Completion: January 1, 2006

Study Registration Dates

• First Submitted: November 23, 2005
• First Submitted That Met QC Criteria: November 23, 2005
• First Posted (Estimate): November 28, 2005

Study Record Updates

• Last Update Posted (Estimate): December 5, 2006
• Last Update Submitted That Met QC Criteria: December 4, 2006
• Last Verified: December 1, 2006

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: P-01-2005