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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00478647
Recruitment Status : Completed
First Posted : May 25, 2007
Results First Posted : September 2, 2010
Last Update Posted : December 14, 2018
Information provided by (Responsible Party):

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Gaucher Disease Biological: GA-GCB (velaglucerase alfa) Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : July 25, 2007
Actual Primary Completion Date : June 26, 2009
Actual Study Completion Date : June 26, 2009

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:
  • gene-activated® human glucocerebrosidase
  • VPRIV®
  • GA-GCB

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. Change From Baseline to Week 53 in Hemoglobin Concentration [ Time Frame: Week 53 ]
  2. Percent Change From Baseline to Week 53 in Platelet Count [ Time Frame: Week 53 ]
  3. 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

  4. 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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   2 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:


  • 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:


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00478647

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

Publications of Results:
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Responsible Party: Shire Identifier: NCT00478647    
Other Study ID Numbers: TKT034
2006-006304-11 ( EudraCT Number )
First Posted: May 25, 2007    Key Record Dates
Results First Posted: September 2, 2010
Last Update Posted: December 14, 2018
Last Verified: November 2018
Keywords provided by Shire:
Acid beta-glucocerebrosidase
Gaucher disease
Enzyme Replacement Therapy
D-glucosyl-N-acylsphingosine glucohydrolase
gene activation
Additional relevant MeSH terms:
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Gaucher Disease
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders