Study of GA-GCB Enzyme Replacement Therapy in Type 1 Gaucher Disease Patients Previously Treated With Imiglucerase - Full Text View

Sponsor:	Shire Human Genetic Therapies, Inc.
Information provided by:	Shire Human Genetic Therapies, Inc.
ClinicalTrials.gov Identifier:	NCT00478647

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 study is to evaluate the safety and efficacy of every other week dosing of GA-GCB (velaglucerase alfa) in patients with type 1 Gaucher disease who were previously treated with imiglucerase.

Condition	Intervention	Phase
Gaucher Disease, Type 1	Biological: GA-GCB (velaglucerase alfa)	Phase II Phase III

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

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:

Patients Which Experienced at Least One Adverse Event [ Time Frame: Week 53 ] [ Designated as safety issue: Yes ]
Safety was assessed throughout the study by assessments including adverse events, concomitant medication use, and vital signs. Additional safety assessments, including 12-lead ECGs, physical examinations, clinical laboratory tests and determination of the presence of anti-velaglucerase alfa antibodies.

Refer to Adverse event section for further details.

Secondary Outcome Measures:

Change From Baseline to Week 53 in Hemoglobin Concentration [ Time Frame: Week 53 ] [ Designated as safety issue: No ]
ITT patient population.
Percent Change From Baseline to Week 53 in Platelet Count [ Time Frame: Week 53 ] [ Designated as safety issue: No ]
ITT patient population.
Percent Change From Baseline to Week 51 in Normalized Liver Volume [ Time Frame: Week 51 ] [ Designated as safety issue: No ]
Liver volume has been normalized for percentage (%) of body weight. Liver size relative to body weight= (Liver volume [cc]/Body weight [kg])*100
Percent Change From Baseline to Week 51 in Normalized Spleen Volume [ Time Frame: Week 51 ] [ Designated as safety issue: No ]
Spleen volume has been normalized for percentage (%) of body weight. Spleen size relative to body weight= (Spleen volume [cc]/Body weight [kg])*100

Enrollment:	40
Study Start Date:	July 2007
Study Completion Date:	August 2009
Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: GA-GCB (velaglucerase alfa)	Biological: GA-GCB (velaglucerase alfa) 15-60 U/kg, every other week via intravenous infusion Other Names: VPRIV® 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 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 safety of GA-GCB in men, women, and children with Type 1 Gaucher disease who were previously treated with imiglucerase. Each patient's duration of treatment will be 12 months.

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 of type 1 Gaucher disease, as determined by deficient glucocerebrosidase (GCB) activity relative to normal as measured in leukocytes or by genotype analysis and the patient/legal guardian is willing and able to provide written informed consent prior to initiating any study-related procedures
The patient has received consistent treatment with imiglucerase at a dose ≤ 60 U/kg and ≥ 15 U/kg every other week for a minimum of 30 consecutive months. Patients who are anti-imiglucerase antibody positive will be allowed to enter this study
The patient is at least 2 years of age
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 co-operative to participate in the 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 investigational drug or device within the 30 days prior to study entry; such use during the study is not permitted
Patient is HIV positive
Patient is hepatitis B/C positive
The patient presents with sustained iron, folic acid and/or vitamin B12 deficiency-related anemia during Screening
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 that might affect study data or confound the study results
The patient is unable to comply with the protocol or is otherwise unlikely to complete the study, as determined by the Investigator
The patient has experienced an anaphylactic/anaphylactoid reaction during treatment with imiglucerase
The patient has received miglustat during the 6 months prior to study enrollment
The patient has an active, clinically significant spleen infarction
The patient has active, progressive bone necrosis
The patient is a pregnant and/or lactating female

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00478647

Locations

United States, California
Regional Metabolic Center
Los Angeles, California, United States, 90027
Children's Hospital Oakland
Oakland, California, United States, 94609
United States, Georgia
Emory University
Decatur, Georgia, United States, 30033
United States, Illinois
Feinberg School of Medicine
Chicago, Illinois, United States, 60614
United States, Minnesota
Children's of Minnesota
Minneapolis, Minnesota, United States, 55404
United States, Missouri
Children's Mercy Hospital and Clinic
Kansas City, Missouri, United States, 64108
United States, New York
NYU School of Medicine
New York, New York, United States, 10016
United States, Ohio
Cincinatti Children's Hospital
Cincinnati, Ohio, United States, 45229
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
United States, Utah
Medical Genetics/Pediatrics
Salt Lake City, Utah, United States, 84132
United States, Wisconsin
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Israel
Shaare Zedek Medical Center
Jerusalem, Israel
Poland
Children's Memorial Health Institute
Warszawa, Poland
Spain
Hospital Universitario Miguel Servet
Zaragoza, Spain, 500009
United Kingdom
The Royal Free Hospital
London, United Kingdom

Sponsors and Collaborators

Shire Human Genetic Therapies, Inc.

Investigators

Study Director:	Eric Crombez, M.D.	Shire Human Genetic Therapies, Inc.
Principal Investigator:	Anna Tylki-Szmanska, M.D.	Children's Memorial Health Institute, Warszawa, Poland
Principal Investigator:	Joel Charrow, M.D.	Feinberg School of Medicine, Chicago, Illinois
Principal Investigator:	Laurie Smith, M.D.	Children's Mercy Hospital and Clinic, Kansas City, Missouri
Principal Investigator:	Ari Zimran, M.D.	Shaare Zedek Medical Center, Jerusalem, Israel
Principal Investigator:	Christine Eng, M.D.	Texas Children's Hospital, Houston, Texas
Principal Investigator:	Paul Fernhoff, M.D.	Emory University, Decatur, Georgia
Principal Investigator:	Gregory Grabowski, M.D.	Cincinatti Children's Hospital, Cincinnati, Ohio
Principal Investigator:	Paul Harmatz, M.D.	Children's Hospital Oakland, Oakland, California
Principal Investigator:	Margaret Heisel Kurth, M.D.	Chidlren's of Minnesota, Minneapolis, Minnesota
Principal Investigator:	Nicola Longo, M.D.	Medical Genetics/Pediatrics, Salt Lake City, Utah
Principal Investigator:	Rebecca Mardach, M.D.	Regional Metabolic Center, Los Angeles, California
Principal Investigator:	Gregory Pastores, M.D.	NYU School of Medicine, New York, New York
Principal Investigator:	William J. Rhead, M.D.	Children's Hospital of Wisconsin, Milwaukee, Wisconsin
Principal Investigator:	Athul Mehta, M.D.	The Royal Free Hosptial, London, United Kingdom
Principal Investigator:	Pilar Giraldo, M.D.	Hospital Universitario Miguel Servet, Zaragoza, Spain

More Information

No publications provided

Responsible Party:	Tiffany Crump, Senior Medical Affairs Associate, Shire Human Genetic Therapies, Inc.
ClinicalTrials.gov Identifier:	NCT00478647 History of Changes
Other Study ID Numbers:	TKT034
Study First Received:	May 23, 2007
Results First Received:	August 4, 2010
Last Updated:	September 20, 2010
Health Authority:	United States: Food and Drug Administration; Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products; Israel: Ministry of Health; United Kingdom: Medicines and Healthcare Products Regulatory Agency; Spain: Spanish Agency of Medicines

Keywords provided by Shire Human Genetic Therapies, Inc.:

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 12, 2012