A Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease (ENGAGE) - Full Text View

Purpose

This Phase 3, Study was designed to confirm the Efficacy and Safety of eliglustat tartrate (Genz-112638) in Patients with Gaucher Disease Type 1

Condition	Intervention	Phase
Gaucher Disease, Type 1	Drug: eliglustat tartrate Drug: Placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study Confirming the Efficacy and Safety of Genz-112638 in Patients With Gaucher Disease Type 1

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

MedlinePlus related topics: Gaucher's Disease

U.S. FDA Resources

Further study details as provided by Genzyme:

Primary Outcome Measures:

Percent change in spleen volume (in multiples of normal (MN)) from Baseline to 39 weeks of treatment with eliglustat tartrate (Genz-112638) as compared to placebo [ Time Frame: 39 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Absolute change in hemoglobin level (g/dL) from Baseline to week 39 [ Time Frame: 39 weeks ] [ Designated as safety issue: No ]
Percent change in liver volume (in MN) from Baseline to week 39 [ Time Frame: 39 weeks ] [ Designated as safety issue: No ]
Percent change in platelet counts from baseline to week 39 [ Time Frame: 39 weeks ] [ Designated as safety issue: No ]

Enrollment:	40
Study Start Date:	November 2009
Estimated Study Completion Date:	January 2015
Primary Completion Date:	July 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Active eliglustat tartrate (Genz-112638)	Drug: eliglustat tartrate Capsule: 50 or 100 mg BID Other Name: Genz-112638
Placebo Comparator: Placebo Placebo	Drug: Placebo Capsule

Detailed Description:

Gaucher disease is characterised by lysosomal accumulation of glucosylceramide due to impaired glucosylceramide hydrolysis. Type 1 Gaucher Disease, the most common form accounts for > 90% of cases and does not involve the central nervous system (CNS). Typical manifestations of type 1 Gaucher Disease include splenomegaly, hepatomegaly, thrombocytopenia, anemia, skeletal pathology and decreased quality of life. The disease manifestations are caused by the accumulations of glucosylceramide (storage material) in Gaucher cells which have infiltrated the spleen and liver as well as other tissue. Eliglustat tartrate (Genz-112638) is a small molecule developed as an oral therapy which acts to specifically inhibit production of this storage material in Gaucher cells.

This study is designed to determine the efficacy, safety, and pharmacokinetics (PK) of eliglustat tartrate (Genz-112638) in adult patients (> 16 years) with Gaucher Disease type 1

Eligibility

Ages Eligible for Study:	16 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

The patient (and/or their parent/legal guardian) is willing and able to provide signed informed consent prior to any study-related procedures to be performed.
The patient is at least 16 years old at the time of randomization.
The patient has a confirmed diagnosis of Gaucher disease type 1.
Female patients of childbearing potential must have a documented negative pregnancy test prior to dosing. In addition all female patients of childbearing potential must use a medically accepted form of contraception throughout the study.

Exclusion Criteria:

The patient has had a partial or total splenectomy.
The patient has received pharmacological chaperones or miglustat within 6 months prior to randomization
The patient has received enzyme replacement therapy within 9 months prior to randomization.
The patient has type 2 or 3 Gaucher Disease or is suspected of having type 3 Gaucher Disease
The patient has any clinically significant disease, other than Gaucher Disease, including cardiovascular, renal, hepatic, gastrointestinal (GI), Pulmonary, neurologic, endocrine, metabolic, (e.g. hypokalemia, hypomagnesemia), or psychiatric disease, other medical conditions, or serious intercurrent illness that may confound the study results, or, on the opinion of the investigator, may preclude participation in the study.
The patient has tested positive for the human immunodeficiency virus (HIV)antibody, Hepatitis C antibody, or Hepatitis B surface antigen.
The patient has received an investigational product within 30 days prior to randomization.
The patient is pregnant or lactating.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00891202

Show 26 Study Locations

Sponsors and Collaborators

Genzyme

Investigators

Study Director:

Medical Monitor

Genzyme

More Information

Publications:

Lukina E, Watman N, Arreguin EA, Banikazemi M, Dragosky M, Iastrebner M, Rosenbaum H, Phillips M, Pastores GM, Rosenthal DI, Kaper M, Singh T, Puga AC, Bonate PL, Peterschmitt MJ. A phase 2 study of eliglustat tartrate (Genz-112638), an oral substrate reduction therapy for Gaucher disease type 1. Blood. 2010 Aug 12;116(6):893-9. Epub 2010 May 3.

Lukina E, Watman N, Arreguin EA, Dragosky M, Iastrebner M, Rosenbaum H, Phillips M, Pastores GM, Kamath RS, Rosenthal DI, Kaper M, Singh T, Puga AC, Peterschmitt MJ. Improvement in hematological, visceral, and skeletal manifestations of Gaucher disease type 1 with oral eliglustat tartrate (Genz-112638) treatment: 2-year results of a phase 2 study. Blood. 2010 Nov 18;116(20):4095-8. Epub 2010 Aug 16.

McEachern KA, Fung J, Komarnitsky S, Siegel CS, Chuang WL, Hutto E, Shayman JA, Grabowski GA, Aerts JM, Cheng SH, Copeland DP, Marshall J. A specific and potent inhibitor of glucosylceramide synthase for substrate inhibition therapy of Gaucher disease. Mol Genet Metab. 2007 Jul;91(3):259-67. Epub 2007 May 16.

Peterschmitt MJ, Burke A, Blankstein L, Smith SE, Puga AC, Kramer WG, Harris JA, Mathews D, Bonate PL. Safety, Tolerability, and Pharmacokinetics of Eliglustat Tartrate (Genz-112638) After Single Doses, Multiple Doses, and Food in Healthy Volunteers. J Clin Pharmacol. 2010 Oct 25; [Epub ahead of print]

Responsible Party:	Genzyme
ClinicalTrials.gov Identifier:	NCT00891202 History of Changes
Other Study ID Numbers:	GZGD02507, 2008-005222-37
Study First Received:	April 30, 2009
Last Updated:	October 12, 2012
Health Authority:	United States: Food and Drug Administration India: Drugs Controller General of India Russia: Ministry of Health of the Russian Federation Netherlands: Medicines Evaluation Board (MEB) Canada: Health Canada United Kingdom: Medicines and Healthcare Products Regulatory Agency Mexico: Ministry of Health Bulgaria: Bulgarian Drug Agency Israel: Israeli Health Ministry Pharmaceutical Administration Jordan: Ethical Committee Tunisia: Office of Pharmacies and Medicines Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos Lebanon: Ministry of Public Health Chile: Ministry of Health Serbia and Montenegro: Agency for Drugs and Medicinal Devices

Keywords provided by Genzyme:

Gaucher,
beta-glucosidase,
acid ß-glucosidase,
glucocerebrosidase,

glucosylceramide,
D-glucosyl-N-acylsphingosine glucohydrolase,
substrate reduction therapy

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 May 19, 2013