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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: June 9, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Gaucher Disease, Type 1
Biological: velaglucerase alfa
Biological: imiglucerase
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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.


Enrollment: 34
Study Start Date: January 2008
Study Completion Date: June 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Cerezyme®

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.

  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00553631

Locations
United States, North Carolina
Duke Children's Hospital & Health Center
Durham, North Carolina, United States, 27710
Argentina
Your Health S.A.
Buenos Aires, Argentina, B1882AQY
India
Malabar Institute of Medical Sciences Ltd.
Calicut, Kerala, India, 673 016
All India Institute of Medical Sciences
New Delhi, India, 110 029
KEM Hospital Research Centre
Pune, India
Israel
Shaare Zedek Medical Center
Jerusalem, Israel
Paraguay
Sociedad Espanola de Socorros Mutuos
Asuncion, Paraguay
Russian Federation
National Research Center for Haematology
Moscow, Russian Federation
Spain
Hospital Universitario Miguel Servet
Zaragoza, Spain
Tunisia
La Rabta Hospital
Tunis, Tunisia
United Kingdom
The Royal Free Hospital
London, United Kingdom
Sponsors and Collaborators
Shire
Investigators
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
  More Information

No publications provided

Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT00553631     History of Changes
Other Study ID Numbers: HGT-GCB-039, 2007-002840-21
Study First Received: November 1, 2007
Results First Received: July 12, 2010
Last Updated: June 9, 2014
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Russia: Ministry of Health of the Russian Federation
Paraguay: Ministerio de Salud Pública y Bienestar Social
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Israel: Ministry of Health
Spain: Spanish Agency of Medicines
India: Drugs Controller General of India
Tunisia: Office of Pharmacies and Medicines

Keywords provided by Shire:
Enzyme Replacement Therapy
Gaucher disease
glucocerebrosidase
beta-glucocerebrosidase
Acid beta-glucocerebrosidase
glucosylceramidase
D-glucosyl-N-acylsphingosine glucohydrolase
gene activation
human

Additional relevant MeSH terms:
Gaucher Disease
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Genetic Diseases, Inborn
Lipid Metabolism Disorders
Lipid Metabolism, Inborn Errors
Lipidoses
Lysosomal Storage Diseases
Lysosomal Storage Diseases, Nervous System
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases
Sphingolipidoses

ClinicalTrials.gov processed this record on November 25, 2014