A Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy in Gaucher Disease

June 28, 2021 updated by: Shire

A Multicenter, Randomized, Double-Blind, Parallel Group, Two-Dose Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy in Patients With Type 1 Gaucher Disease

Gaucher disease is a rare lysosomal storage disorder caused by the deficiency of the enzyme glucocerebrosidase (GCB). Due to this deficiency of functional GCB, glucocerebroside accumulates within macrophages leading to cellular engorgement, organomegaly, and organ system dysfunction. The purpose of this study is to evaluate the efficacy of every other week dosing of Gene-Activated® Human Glucocerebrosidase (GA-GCB, velaglucerase alfa) at doses of 45 and 60 U/kg in treatment-naïve patients with type 1 Gaucher disease.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Type 1 Gaucher disease, the most common form, accounts for more than 90% of all cases and does not involve the Central Nervous System (CNS). Typical manifestations of type 1 Gaucher disease include hepatomegaly, splenomegaly, thrombocytopenia, bleeding tendencies, anemia, hypermetabolism, skeletal pathology, growth retardation, pulmonary disease, and decreased quality of life. Gene-Activated® human glucocerebrosidase (GA-GCB; velaglucerase alfa) is produced in a continuous human cell line using proprietary gene-activation technology and has an identical amino acid sequence to the naturally occurring human enzyme. Velaglucerase alfa contains terminal mannose residues that target the enzyme to the macrophages-the primary target cells in Gaucher disease. This study was designed to determine the efficacy, safety and pharmacokinetics of GA-GCB in men, women, and children with Type 1 Gaucher disease. Each patients duration of treatment was 12 months.

Study Type

Interventional

Enrollment (Actual)

25

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina
        • Hipolito Yrigoyen
  • Israel
      • Jerusalem, Israel
        • Shaare Zedek Medical Center
  • Paraguay
      • Asuncion, Paraguay
        • Sociedad Espanola de Socorros Mutuos
  • Russian Federation
      • Moscow, Russian Federation
        • National Research Center for Haematology
  • Tunisia
      • Tunis, Tunisia
        • La Rabta Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patient has a documented diagnosis of type 1 Gaucher disease, as determined by deficient glucocerebrosidase (GCB) activity relative to normal as measured in leukocytes or by genotype analysis and is willing and able to provide written informed consent prior to initiating any study-related procedures
  • Patient is at least 2 years of age
  • Patient has Gaucher disease-related anemia and
  • Patient has at least moderate splenomegaly or
  • Patient has Gaucher disease-related thrombocytopenia or
  • Patient has a readily palpable enlarged liver
  • Patient has not received treatment for Gaucher disease within 30 months prior to study entry
  • Female patients of child-bearing potential agree to use a medically acceptable method of contraception. Male patients must agree to use a medically acceptable method of birth control.
  • Patient must be sufficiently cooperative to participate in the study as judged by the Investigator.

Exclusion Criteria:

Includes:

  • Patient has type 2 or 3 Gaucher disease or is suspected of having type 3 Gaucher disease
  • Patient is antibody-positive to imiglucerase during screening or has experienced an anaphylactic reaction to imiglucerase
  • Patient has received treatment with any investigational drug or device within the 30 days prior to study entry
  • Patient is Human immunodeficiency virus (HIV) positive
  • Patient is hepatitis positive
  • Patient presents with iron, folic acid and/or vitamin B12 deficiency sustained anemia during screening
  • Patient, patient's parent(s), or patient's legal guardian(s) is/are unable to understand the nature, scope, and possible consequences of the study
  • Patient has a significant comorbidity(ies)that might affect study data or confound the study results
  • Patient is a pregnant and/or lactating female
  • Patient is unable to comply with the protocol or is unlikely to complete the study, as determined by the Investigator

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: VPRIV®-45 U/kg, IV, every other week
VPRIV® (velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB)
Biological: VPRIV ®,
Intravenous (IV) infusion, every other week via intravenous infusion for 12 months
Other Names:
  • velaglucerase alfa
  • VPRIV®
  • GA-GCB
  • Gene-activated® human glucocerebrosidase
Experimental: VPRIV®-60 U/kg, IV, every other week
VPRIV® (velaglucerase alfa, Gene Activated® human glucocerebrosidase,GA-GCB)
Biological: VPRIV ®,
Intravenous (IV) infusion, every other week via intravenous infusion for 12 months
Other Names:
  • velaglucerase alfa
  • VPRIV®
  • GA-GCB
  • Gene-activated® human glucocerebrosidase

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline to 12 Months in Hemoglobin Concentration for the 60 U/kg Treatment Group.
Time Frame: Week 53
Efficacy endpoint
Week 53

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline to 12 Months in Hemoglobin Concentration in 45 U/kg Treatment Group
Time Frame: Week 53
Week 53
Change From Baseline to 12 Months in Platelet Counts for Each Treatment Group.
Time Frame: Week 53
intent to treat (ITT) Population
Week 53
Change From Baseline to 12 Months in Normalized Liver Volume (Percent Body Weight) for Each Treatment Group (Measured by Magnetic Resonance Imaging (MRI)
Time Frame: Week 51
Liver Volume has been normalized for percentage of body weight for each treatment arm. Liver size relative to body weight = (Liver volume [cc]/Body weight [kg])*100
Week 51
Change From Baseline to 12 Months in Normalized Spleen Volume (Percent Body Weight) for Each Treatment Group (Measured by Magnetic Resonance Imaging (MRI))
Time Frame: Week 51
12 patients in the 60 U/kg group and 13 patients in the 45 U/kg group were analyzed for efficacy in the intent to treat (ITT) population. Spleen Volume has been normalized for percent of body weight for each treatment arm. Spleen size relative to body weight = (Spleen volume [cc]/Body weight [kg])*100
Week 51
Percent Change From Baseline to 12 Months in Plasma Chitotriosidase for Each Treatment Group
Time Frame: Week 53
Percent Change from Baseline to Weeks 53 by Randomized velaglucerase alfa Treatment Group - Subset of intent to treat (ITT) Population who were wild type homozygous for chitotriosidase.
Week 53
Percent Change From Baseline to 12 Months in Chemokine (C-C Motif) Ligand 18 (CCL18)
Time Frame: Week 53
Week 53

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shire

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 15, 2007

Primary Completion (Actual)

April 1, 2009

Study Completion (Actual)

April 1, 2009

Study Registration Dates

First Submitted

February 1, 2007

First Submitted That Met QC Criteria

February 1, 2007

First Posted (Estimate)

February 2, 2007

Study Record Updates

Last Update Posted (Actual)

June 29, 2021

Last Update Submitted That Met QC Criteria

June 28, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TKT032

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Gaucher Disease, Type 1

Clinical Trials on VPRIV ®,

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Qatar

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe