A Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy in Gaucher Disease - Full Text View

Sponsor:	Shire Human Genetic Therapies, Inc.
Information provided by:	Shire Human Genetic Therapies, Inc.
ClinicalTrials.gov Identifier:	NCT00430625

Purpose

Gaucher disease is a rare lysosomal storage disorder caused by the deficiency of the enzyme glucocerebrosidase (GCB). Due to this 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 efficacy of every other week dosing of Gene-Activated® Human Glucocerebrosidase (GA-GCB, velaglucerase alfa) at doses of 45 and 60 U/kg in treatment-naïve patients with type 1 Gaucher disease.

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

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Multicenter, Randomized, Double-Blind, Parallel Group, Two-Dose Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy in Patients With Type 1 Gaucher Disease

Resource links provided by NLM:

Genetics Home Reference related topics: Chanarin-Dorfman syndrome cholesteryl ester storage disease Farber lipogranulomatosis Gaucher disease Schindler disease succinic semialdehyde dehydrogenase deficiency Help Me Understand Genetics

MedlinePlus related topics: Gaucher's Disease

Drug Information available for: Alglucerase Imiglucerase

U.S. FDA Resources

Further study details as provided by Shire Human Genetic Therapies, Inc.:

Primary Outcome Measures:

Change From Baseline to 12 Months in Hemoglobin Concentration for the 60 U/kg Treatment Group. [ Time Frame: Week 53 ] [ Designated as safety issue: No ]
Efficacy endpoint

Secondary Outcome Measures:

Change From Baseline to 12 Months in Hemoglobin Concentration in 45 U/kg Treatment Group [ Time Frame: Week 53 ] [ Designated as safety issue: No ]
Change From Baseline to 12 Months in Platelet Counts for Each Treatment Group. [ Time Frame: Week 53 ] [ Designated as safety issue: No ]
intent to treat (ITT) Population
Change From Baseline to 12 Months in Normalized Liver Volume (Percent Body Weight) for Each Treatment Group (Measured by Magnetic Resonance Imaging (MRI) [ Time Frame: Week 51 ] [ Designated as safety issue: No ]
Liver Volume has been normalized for percentage of body weight for each treatment arm. Liver size relative to body weight = (Liver volume [cc]/Body weight [kg])*100
Change From Baseline to 12 Months in Normalized Spleen Volume (Percent Body Weight) for Each Treatment Group (Measured by Magnetic Resonance Imaging (MRI)) [ Time Frame: Week 51 ] [ Designated as safety issue: No ]
12 patients in the 60 U/kg group and 13 patients in the 45 U/kg group were analyzed for efficacy in the intent to treat (ITT) population. Spleen Volume has been normalized for percent of body weight for each treatment arm. Spleen size relative to body weight = (Spleen volume [cc]/Body weight [kg])*100
Percent Change From Baseline to 12 Months in Plasma Chitotriosidase for Each Treatment Group [ Time Frame: Week 53 ] [ Designated as safety issue: No ]
Percent Change from Baseline to Weeks 53 by Randomized velaglucerase alfa Treatment Group - Subset of intent to treat (ITT) Population who were wild type homozygous for chitotriosidase.
Percent Change From Baseline to 12 Months in Chemokine (C-C Motif) Ligand 18 (CCL18) [ Time Frame: Week 53 ] [ Designated as safety issue: No ]

Enrollment:	25
Study Start Date:	January 2007
Study Completion Date:	May 2009
Primary Completion Date:	April 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: VPRIV®-45 U/kg, IV, every other week VPRIV® (velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB)	Biological: VPRIV ®, Intravenous (IV) infusion, every other week via intravenous infusion for 12 months Other Names: VPRIV® velaglucerase alfa GA-GCB Gene-activated® human glucocerebrosidase
Experimental: VPRIV®-60 U/kg, IV, every other week VPRIV® (velaglucerase alfa, Gene Activated® human glucocerebrosidase,GA-GCB)	Biological: VPRIV ®, Intravenous (IV) infusion, every other week via intravenous infusion for 12 months Other Names: VPRIV® velaglucerase alfa GA-GCB Gene-activated® human glucocerebrosidase

Detailed Description:

Type 1 Gaucher disease, the most common form, accounts for more than 90% of all cases and does not involve the Central Nervous System (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. 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, safety and pharmacokinetics of GA-GCB in men, women, and children with Type 1 Gaucher disease. Each patients duration of treatment was 12 months.

Eligibility

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

Criteria

Inclusion Criteria:

Patient 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 is willing and able to provide written informed consent prior to initiating any study-related procedures
Patient is at least 2 years of age
Patient has Gaucher disease-related anemia and
Patient has at least moderate splenomegaly or
Patient has Gaucher disease-related thrombocytopenia or
Patient has a readily palpable enlarged liver
Patient has not received treatment for Gaucher disease within 30 months prior to study entry
Female patients of child-bearing potential agree to use a medically acceptable method of contraception. Male patients must agree to use a medically acceptable method of birth control.
Patient must be sufficiently cooperative to participate in the study as judged by the Investigator.

Exclusion Criteria:

Includes:

Patient has type 2 or 3 Gaucher disease or is suspected of having type 3 Gaucher disease
Patient is antibody-positive to imiglucerase during screening or has experienced an anaphylactic reaction to imiglucerase
Patient has received treatment with any investigational drug or device within the 30 days prior to study entry
Patient is Human immunodeficiency virus (HIV) positive
Patient is hepatitis positive
Patient presents with iron, folic acid and/or vitamin B12 deficiency sustained anemia during screening
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
Patient has a significant comorbidity(ies)that might affect study data or confound the study results
Patient is a pregnant and/or lactating female
Patient is unable to comply with the protocol or is unlikely to complete the study, as determined by the Investigator

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00430625

Locations

Argentina
Hipolito Yrigoyen
Buenos Aires, Argentina
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
Tunisia
La Rabta Hospital
Tunis, Tunisia

Sponsors and Collaborators

Shire Human Genetic Therapies, Inc.

Investigators

Study Director:	Kiran Bhirangi, M.D., FRCS	Shire Human Genetic Therapies, Inc.
Principal Investigator:	Ari Zimran, M.D.	Shaare Zedek Medical Center
Principal Investigator:	Derlis Emilio Gonzalez Rodriguez, M.D.	Sociedad Espanola de Socorros Mutuos
Principal Investigator:	Marie-Francoise Ben Dridi, Professor	La Rabta Hospital
Principal Investigator:	Isaac Kisinovsky, M.D.	Hipolito Yrigoyen
Principal Investigator:	Elena A. Lukina, Professor	National Research Center for Haematology

More Information

Additional Information:

Shire product Information web site This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Tiffany Crump, Medical Communications Manager, Shire Human Genetic Therapies, Inc.
ClinicalTrials.gov Identifier:	NCT00430625 History of Changes
Other Study ID Numbers:	TKT032
Study First Received:	February 1, 2007
Results First Received:	June 3, 2010
Last Updated:	August 19, 2010
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; Russia: Ministry of Health and Social Development of the Russian Federation; Tunisia: Office of Pharmacies and Medicines

Keywords provided by Shire Human Genetic Therapies, Inc.:

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
Sphingolipidoses
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
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders

ClinicalTrials.gov processed this record on February 09, 2012