An Open-Label Extension Study of GA-GCB ERT in Patients With Type 1 Gaucher Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT00635427
First received: March 6, 2008
Last updated: June 9, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to evaluate the long-term safety of every other week dosing of Gene-Activated® human glucocerebrosidase (GA-GCB, velaglucerase alfa) intravenously in patients with type 1 Gaucher disease.


Condition Intervention Phase
Gaucher Disease, Type 1
Biological: VPRIV®
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label Extension Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy in Patients With Type 1 Gaucher Disease

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • Overall Summary of Treatment Emergent Adverse Events [ Time Frame: Baseline to termination of study ] [ Designated as safety issue: Yes ]
    Safety was evaluated by an analysis of AEs, concomitant medication use, clinical laboratory tests, vital signs during the infusion of study drug, physical examination, and the development of anti-velaglucerase alfa. No formal comparisons or statistical tests were applied for the safety analyses, including for differences between the groups.


Secondary Outcome Measures:
  • Change From Baseline to 24 Months in Hemoglobin Concentration for Each Treatment Group [ Time Frame: Baseline to 24 months ] [ Designated as safety issue: No ]
  • Change From Baseline to 24 Months in Platelet Counts for Each Treatment Group [ Time Frame: Baseline to 24 months ] [ Designated as safety issue: No ]
  • Change From Baseline to 24 Months in Normalized Liver Volume for Each Treatment Group [ Time Frame: Baseline to 24 months ] [ Designated as safety issue: No ]
  • Percentage Change From Baseline to 24 Months in Normalized Spleen Volume for Each Treatment Group [ Time Frame: Baseline to 24 months ] [ Designated as safety issue: No ]

Enrollment: 95
Study Start Date: May 2008
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: VPRIV 60 U/kg(VPRIV Parent Study 45 or 60 U/kg- TKT032,GCB039)

This arm is the Overall velaglucerase alfa (VPRIV) 60 U/kg and includes patients from the following groups:

VPRIV 45 U/kg or 60 U/kg, IV, EOW for 51 weeks in parent study TKT032 (NCT00430625) and switched to 60 U/kg in HGT-GCB-044 to maintain blindness or 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631)

Biological: VPRIV®
Intravenous infusion, every other week (EOW)
Other Names:
  • velaglucerase alfa
  • VPRIV®
  • Gene-Activated® Human Glucocerebrosidase(GA-GCB)
Experimental: VPRIV 60 U/kg (Parent study-imiglucerase(60 U/kg) HGT-GCB-039)
imiglucerase 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631)and switched 60 U/kg VPRIV in HGT-GCB-044
Biological: VPRIV®
Intravenous infusion, every other week (EOW)
Other Names:
  • velaglucerase alfa
  • VPRIV®
  • Gene-Activated® Human Glucocerebrosidase(GA-GCB)
Experimental: VPRIV 15-60 U/kg (Parent study VPRIV (15-50 U/kg) TKT034)
VPRIV 15- 60 U/kg, IV, EOW for 51 weeks in parent study TKT034 (NCT00478647) and continued in HGT-GCB-044 at the same dose as prescribed in TKT034
Biological: VPRIV®
Intravenous infusion, every other week (EOW)
Other Names:
  • velaglucerase alfa
  • VPRIV®
  • Gene-Activated® Human Glucocerebrosidase(GA-GCB)

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 long-term safety of GA-GCB 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:

  1. The patient has completed study TKT032 or TKT034, or study HGT-GCB-039.
  2. 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.
  3. Male patients must agree to use a medically acceptable method of contraception at all times during the study and report a partner's pregnancy to the investigator.
  4. 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).
  5. The patient must be sufficiently cooperative to participate in this clinical study as judged by the Investigator

Exclusion Criteria:

  1. 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.
  2. The patient is pregnant or lactating.
  3. 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.
  4. 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.).
  5. 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: NCT00635427

  Show 21 Study Locations
Sponsors and Collaborators
Shire
Investigators
Study Director: Eric Crombez, M.D. Shire Human Genetic Therapies, Inc.
  More Information

No publications provided

Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT00635427     History of Changes
Other Study ID Numbers: HGT-GCB-044, 2008-001965-27
Study First Received: March 6, 2008
Results First Received: December 11, 2013
Last Updated: June 9, 2014
Health Authority: United States: Food and Drug Administration
Paraguay: Ministerio de Salud Pública y Bienestar Social
Israel: Ministry of Health
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Poland: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
India: Drugs Controller General of India
South Korea: Korea Food and Drug Administration (KFDA)
Russia: Ministry of Health of the Russian Federation
Spain: Ministry of Health and Consumption
Tunisia: Ministry of Public Health

Keywords provided by Shire:
VPRIV
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 October 22, 2014