Study of GA-GCB Enzyme Replacement Therapy in Type 1 Gaucher Disease Patients Previously Treated With Imiglucerase

May 26, 2021 updated by: Shire

A Multicenter Open-Label Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy in Patients With Type 1 Gaucher Disease Previously Treated With Imiglucerase

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 study is to evaluate the safety and efficacy of every other week dosing of GA-GCB (velaglucerase alfa) in participants with type 1 Gaucher disease who were previously treated with imiglucerase.

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 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 safety of GA-GCB in men, women, and children with Type 1 Gaucher disease who were previously treated with imiglucerase. Each participant's duration of treatment will be 12 months.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 2
  • 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

  • Israel
      • Jerusalem, Israel
        • Shaare Zedek Medical Center
  • Poland
      • Warszawa, Poland
        • Children's Memorial Health Institute
  • Spain
      • Zaragoza, Spain, 500009
        • Hospital Universitario Miguel Servet
  • United Kingdom
      • London, United Kingdom
        • The Royal Free Hospital
  • United States
    • California
      • Los Angeles, California, United States, 90027
        • Regional Metabolic Center
      • Oakland, California, United States, 94609
        • Children's Hospital Oakland
    • Georgia
      • Decatur, Georgia, United States, 30033
        • Emory University
    • Illinois
      • Chicago, Illinois, United States, 60614
        • Feinberg School of Medicine
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Children's of Minnesota
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Children's Mercy Hospital and Clinic
    • New York
      • New York, New York, United States, 10016
        • NYU School of Medicine
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinatti Children's Hospital
    • Texas
      • Houston, Texas, United States, 77030
        • Texas Children's Hospital
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • Medical Genetics/Pediatrics
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Children's Hospital of Wisconsin

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 (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Includes:

  • The participant 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 the participant/legal guardian is willing and able to provide written informed consent prior to initiating any study-related procedures
  • The participant has received consistent treatment with imiglucerase at a dose ≤ 60 U/kg and ≥ 15 U/kg every other week for a minimum of 30 consecutive months. Participants who are anti-imiglucerase antibody positive will be allowed to enter this study
  • The participant is at least 2 years of age
  • Female participants of child-bearing potential agree to use a medically acceptable method of contraception. Male participants must agree to use a medically acceptable method of birth control
  • Participant must be sufficiently co-operative to participate in the study as judged by the Investigator.

Exclusion Criteria:

Includes:

  • The participant has type 2 or 3 Gaucher disease or is suspected of having type 3 Gaucher disease
  • The participant has received treatment with any investigational drug or device within the 30 days prior to study entry; such use during the study is not permitted
  • Participant is HIV positive
  • Participant is hepatitis B/C positive
  • The participant presents with sustained iron, folic acid and/or vitamin B12 deficiency-related anemia during Screening
  • The participant, participant's parent(s), or participant's legal guardian(s) is/are unable to understand the nature, scope, and possible consequences of the study
  • The participant has a significant comorbidity that might affect study data or confound the study results
  • The participant is unable to comply with the protocol or is otherwise unlikely to complete the study, as determined by the Investigator
  • The participant has experienced an anaphylactic/anaphylactoid reaction during treatment with imiglucerase
  • The participant has received miglustat during the 6 months prior to study enrollment
  • The participant has an active, clinically significant spleen infarction
  • The participant has active, progressive bone necrosis
  • The participant is a pregnant and/or lactating female

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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: GA-GCB (velaglucerase alfa)
15-60 U/kg, every other week via intravenous infusion
Biological: GA-GCB (velaglucerase alfa)
15-60 U/kg, every other week via intravenous infusion
Other Names:
  • VPRIV®
  • GA-GCB
  • gene-activated® human glucocerebrosidase

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Participants Who Experienced at Least One Adverse Event
Time Frame: Week 53
Safety was assessed throughout the study by assessments including adverse events, concomitant medication use, and vital signs. Additional safety assessments, including 12-lead ECGs, physical examinations, clinical laboratory tests and determination of the presence of anti-velaglucerase alfa antibodies. Refer to Adverse event section for further details.
Week 53

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline to Week 53 in Hemoglobin Concentration
Time Frame: Week 53
Week 53
Percent Change From Baseline to Week 53 in Platelet Count
Time Frame: Week 53
Week 53
Percent Change From Baseline to Week 51 in Normalized Liver Volume
Time Frame: Week 51
Liver volume has been normalized for percentage (%) of body weight. Liver size relative to body weight= (Liver volume [cc]/Body weight [kg])*100
Week 51
Percent Change From Baseline to Week 51 in Normalized Spleen Volume
Time Frame: Week 51
Spleen volume has been normalized for percentage (%) of body weight. Spleen size relative to body weight= (Spleen volume [cc]/Body weight [kg])*100
Week 51

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)

July 25, 2007

Primary Completion (ACTUAL)

June 26, 2009

Study Completion (ACTUAL)

June 26, 2009

Study Registration Dates

First Submitted

May 23, 2007

First Submitted That Met QC Criteria

May 23, 2007

First Posted (ESTIMATE)

May 25, 2007

Study Record Updates

Last Update Posted (ACTUAL)

June 10, 2021

Last Update Submitted That Met QC Criteria

May 26, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TKT034
  • 2006-006304-11 (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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