Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) ERT Compared With Imiglucerase in Type I Gaucher Disease

May 14, 2021 updated by: Shire

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

Gaucher disease is a rare lysosomal storage disorder caused by the deficiency of the enzyme glucocerebrosidase (GCB). Due to the deficiency of functional GCB, glucocerebroside accumulates within macrophages leading to cellular engorgement, organomegaly, and organ system dysfunction. The purpose of this non-inferiority study is to evaluate the efficacy and safety of GA-GCB (velaglucerase alfa) administered every other week in comparison to imiglucerase in treatment naive 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 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. GA-GCB (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 and safety of GA-GCB (velaglucerase alfa) in comparison to imiglucerase in men, women, and children with Type 1 Gaucher disease.

Study Type

Interventional

Enrollment (Actual)

34

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, B1882AQY
        • Your Health S.A.
  • India
      • New Delhi, India, 110 029
        • All India Institute of Medical Sciences
      • Pune, India
        • KEM Hospital Research Centre
    • Kerala
      • Calicut, Kerala, India, 673 016
        • Malabar Institute of Medical Sciences Ltd.
  • 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
  • Spain
      • Zaragoza, Spain
        • Hospital Universitario Miguel Servet
  • Tunisia
      • Tunis, Tunisia
        • La Rabta Hospital
  • United Kingdom
      • London, United Kingdom
        • The Royal Free Hospital
  • United States
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke Children's Hospital & Health Center

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

2 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Includes:

  • The patient has a documented diagnosis and clinical manifestation of type 1 Gaucher disease
  • The patient is at least 2 years of age.
  • The patient has not received treatment for Gaucher disease (investigational products, miglustat, or imiglucerase) within 12 months prior to study entry, as documented in the patient's medical history.
  • Female patients of child-bearing potential must agree to use a medically acceptable method of contraception at all times during the study and must have negative results to a pregnancy test performed at the time of enrollment and as required throughout their participation in the study. Male patients must use a medically acceptable method of birth control throughout their participation in the study and must report their partner's pregnancy.
  • The patient, the patient's parent(s) or legal guardian(s) has provided written informed consent that has been approved by the Institutional Review Board/Independent Ethics Committee (IRB/IEC).
  • The patient must be sufficiently cooperative to participate in this clinical study as judged by the Investigator.

Exclusion Criteria

Includes:

  • The patient has type 2 or 3 Gaucher disease or is suspected of having type 3 Gaucher disease.
  • The patient has received treatment with any non-Gaucher disease-related investigational drug or device within the 30 days prior to study entry; such use during the study is not permitted.
  • The patient is known to be positive for human immunodeficiency virus (HIV).
  • The patient is known to be positive for hepatitis B and/or C.
  • The 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.
  • The patient has a significant comorbidity(ies) that might affect study data or confound the study results (e.g., malignancies, primary biliary cirrhosis, autoimmune liver disease, etc.).
  • The patient is unable to comply with the protocol, e.g., has a clinically relevant medical condition making implementation of the protocol difficult, has an uncooperative attitude, is unable to return for safety evaluations, or is otherwise 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: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: GA-GCB
VPRIV™ ,velaglucerase alfa
Biological: velaglucerase alfa
IV infusion, 60 U/kg every other week for 9 months
Other Names:
  • VPRIV™
  • gene-activated human glucocerebrosidase
Active Comparator: imiglucerase
Biological: imiglucerase
IV infusion, 60 U/kg every other week for 9 months
Other Names:
  • Cerezyme®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Mean Change From Baseline to Month 9 in Hemoglobin (Hgb) Concentration for Each Treatment Group.
Time Frame: Baseline to Month 9
Baseline to Month 9

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline to Month 9 in Platelet Counts for Each Treatment Group.
Time Frame: Baseline to Month 9
Values shown are observed change from Baseline to Month 9.
Baseline to Month 9
Change From Baseline to Month 9 in Normalized Liver Volume (Percent (%) Body Weight) for Each Treatment Group.
Time Frame: Baseline to Month 9
Values shown are observed change from Baseline to Month 9. Measured by Magnetic resonance imaging (MRI). Liver volume has been normalized for percent (%) body weight for each treatment arm. Liver size relative to body weight = (Liver volume [cubic centimeter (cc)]/Body weight [kg]*1000.
Baseline to Month 9
Change From Baseline to Month 9 in Normalized Spleen Volume (Percent (%) Body Weight) for Each Treatment Group.
Time Frame: Baseline to Month 9
Values shown are observed change from Baseline to month 9. Measured by Magnetic resonance imaging (MRI). Spleen volume was normalized for percent (%) of body weight for each treatment arm. Spleen size relative to body weight=(Spleen volume [cc]/Body weight [kg])*100.
Baseline to Month 9
Change From Baseline to Month 9 in Plasma Chitotriosidase for Each Treatment Group.
Time Frame: Baseline to Month 9.
Values shown are observed change from Baseline to Month 9. Units of measure is defined as nanomole per milliliter per hour.
Baseline to Month 9.
Change From Baseline to Month 9 in Plasma Chemokine (C-C Motif) Ligand 18 (CCL18) for Each Treatment Group.
Time Frame: Baseline to Month 9
Values shown are observed change from Baseline to Month 9.
Baseline to Month 9
Number of Participants Who Developed Antibody for Each Treatment Group.
Time Frame: Baseline to Month 9
Measure type is actual number of participants who developed antibodies to treatment; GA-GCB or imiglucerase. Antibody detection was based upon serum samples collected at various time points throughout the study. Serum samples were screened using an enzyme-linked immunosorbent assay (ELISA) and positive antibody confirmation was determined using a radioimmunoprecipitation assay (RIP); positive samples were also tested for enzyme neutralizing activity. Participant samples were compared to internal assay controls (positive/negative), positive samples were determined based upon individual assay criteria.
Baseline to Month 9
Time to Response- Comparison of GA-GCB and Imiglucerase on the Earliest Time to Respond as Assessed Via Hemoglobin Concentration
Time Frame: Response rate at Month 9 compared to Baseline
Time to response was defined as a ≥ 1 g/dL improvement in hemoglobin levels relative to Baseline. Units (%) correlates to the percentage of participants who had a change of ≥ 1 g/dL improvement in hemoglobin levels relative to Baseline during their participation in the study.
Response rate at Month 9 compared to Baseline

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

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)

January 29, 2008

Primary Completion (Actual)

May 5, 2009

Study Completion (Actual)

May 5, 2009

Study Registration Dates

First Submitted

November 1, 2007

First Submitted That Met QC Criteria

November 1, 2007

First Posted (Estimate)

November 4, 2007

Study Record Updates

Last Update Posted (Actual)

June 8, 2021

Last Update Submitted That Met QC Criteria

May 14, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HGT-GCB-039
  • 2007-002840-21 (EudraCT Number)

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.

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