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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT00553631
First received: November 1, 2007
Last updated: February 19, 2014
Last verified: February 2014

November 1, 2007
February 19, 2014
January 2008
May 2009   (final data collection date for primary outcome measure)
Mean Change From Baseline to Month 9 in Hemoglobin (Hgb) Concentration for Each Treatment Group. [ Time Frame: Baseline to Month 9 ] [ Designated as safety issue: No ]
The primary objective of this study is to compare the effects of GA-GCB and imiglucerase in patients with type 1 Gaucher disease.
Complete list of historical versions of study NCT00553631 on ClinicalTrials.gov Archive Site
  • Change From Baseline to Month 9 in Platelet Counts for Each Treatment Group. [ Time Frame: Baseline to Month 9 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 [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 ] [ Designated as safety issue: No ]
    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. Ten patients in each treatment group were splenectomized and therefore excluded from the analysis.
  • Change From Baseline to Month 9 in Plasma Chitotriosidase for Each Treatment Group. [ Time Frame: Baseline to Month 9. ] [ Designated as safety issue: No ]
    Values shown are observed change from Baseline to Month 9. Chitotriosidase levels were measured in 10 patients in the velaglucerase alfa group and 11 patients in the imiglucerase group. 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 ] [ Designated as safety issue: No ]
    Values shown are observed change from Baseline to Month 9.
  • Number of Patients Who Developed Antibody for Each Treatment Group. [ Time Frame: Baseline to Month 9 ] [ Designated as safety issue: Yes ]
    Measure type is actual number of patients 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. Patient 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 Assesed Via Hemoglobin Concentration [ Time Frame: Response rate at Month 9 compared to Baseline ] [ Designated as safety issue: No ]
    Time to response was defined as a ≥ 1 g/dL improvement in hemoglobin levels relative to Baseline. Units (%) correlates to the percentage of patients who had a change of ≥ 1 g/dL improvement in hemoglobin levels relative to Baseline during their participation in the study.
Secondary objectives include: Comparison of effect on disease-specific biomarkers and the evaluation of safety.
Not Provided
Not Provided
 
Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) ERT Compared With Imiglucerase in Type I Gaucher Disease
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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Gaucher Disease, Type 1
  • 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®
  • Experimental: GA-GCB
    VPRIV™ ,velaglucerase alfa
    Intervention: Biological: velaglucerase alfa
  • Active Comparator: imiglucerase
    Intervention: Biological: imiglucerase
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
34
June 2009
May 2009   (final data collection date for primary outcome measure)

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.
Both
2 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   India,   Israel,   Paraguay,   Russian Federation,   Spain,   Tunisia,   United Kingdom
 
NCT00553631
HGT-GCB-039
No
Shire
Shire
Not Provided
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
Shire
February 2014

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