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

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.
 
ClinicalTrials.gov Identifier: NCT00553631
Recruitment Status : Completed
First Posted : November 4, 2007
Results First Posted : January 4, 2011
Last Update Posted : August 7, 2015
Sponsor:
Information provided by (Responsible Party):
Shire

Tracking Information
First Submitted Date  ICMJE November 1, 2007
First Posted Date  ICMJE November 4, 2007
Results First Submitted Date  ICMJE July 12, 2010
Results First Posted Date  ICMJE January 4, 2011
Last Update Posted Date August 7, 2015
Study Start Date  ICMJE January 2008
Actual Primary Completion Date May 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 3, 2010)
Mean Change From Baseline to Month 9 in Hemoglobin (Hgb) Concentration for Each Treatment Group. [ Time Frame: Baseline to Month 9 ]
Original Primary Outcome Measures  ICMJE
 (submitted: November 1, 2007)
The primary objective of this study is to compare the effects of GA-GCB and imiglucerase in patients with type 1 Gaucher disease.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 16, 2015)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 1, 2007)
Secondary objectives include: Comparison of effect on disease-specific biomarkers and the evaluation of safety.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) ERT Compared With Imiglucerase in Type I Gaucher Disease
Official Title  ICMJE 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
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 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Gaucher Disease, Type 1
Intervention  ICMJE
  • Biological: velaglucerase alfa
    IV infusion, 60 U/kg every other week for 9 months
    Other Names:
    • VPRIV™
    • gene-activated human glucocerebrosidase
  • Biological: imiglucerase
    IV infusion, 60 U/kg every other week for 9 months
    Other Name: Cerezyme®
Study Arms  ICMJE
  • Experimental: GA-GCB
    VPRIV™ ,velaglucerase alfa
    Intervention: Biological: velaglucerase alfa
  • Active Comparator: imiglucerase
    Intervention: Biological: imiglucerase
Publications * Zimran A, Elstein D, Gonzalez DE, Lukina EA, Qin Y, Dinh Q, Turkia HB. Treatment-naïve Gaucher disease patients achieve therapeutic goals and normalization with velaglucerase alfa by 4years in phase 3 trials. Blood Cells Mol Dis. 2018 Feb;68:153-159. doi: 10.1016/j.bcmd.2016.10.007. Epub 2016 Oct 21.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 3, 2010)
34
Original Estimated Enrollment  ICMJE
 (submitted: November 1, 2007)
32
Actual Study Completion Date  ICMJE June 2009
Actual Primary Completion Date May 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   India,   Israel,   Paraguay,   Russian Federation,   Spain,   Tunisia,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00553631
Other Study ID Numbers  ICMJE HGT-GCB-039
2007-002840-21 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Shire
Study Sponsor  ICMJE Shire
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Kiran Bhirangi, M.D. Shire Human Genetic Therapies, Inc.
Principal Investigator: Priya Kishnani, M.D. Duke Children's Hospital & Health Center
Principal Investigator: Isaac Kisinovsky, M.D. Your Health S.A. (Hipolito Yrigoyen)
Principal Investigator: Derlis Gonzalez Rodriguez, M.D. Sociedad Espanola de Socorros Mutuos
Principal Investigator: Elena A. Lukina, M.D. National Research Center for Haematology
Principal Investigator: Atul Mehta, M.D. The Royal Free Hospital
Principal Investigator: Ari Zimran, M.D. Shaare Zedek Medical Center
Principal Investigator: Pilar Giraldo, M.D. Hospital Universitario Miguel Servet
Principal Investigator: Suresh Kumar, M.D. Malabar Institute of Medical Sciences Ltd.
Principal Investigator: Madhulika Kabra, M.D. All India Institute of Medical Sciences, New Delhi
Principal Investigator: Ashish Bavdekar, M.D. KEM Hospital Research Centre
Principal Investigator: Marie-Francoise Ben Dridi, M.D. La Rabta Hospital
PRS Account Shire
Verification Date February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP