A Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease Who Have Reached Therapeutic Goals With Enzyme Replacement Therapy (ENCORE) - Full Text View

Sponsor:	Genzyme
Information provided by (Responsible Party):	Genzyme
ClinicalTrials.gov Identifier:	NCT00943111

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 who have reached therapeutic goals with enzyme replacement therapy.

Condition	Intervention	Phase
Gaucher Disease, Type 1	Drug: eliglustat tartrate Drug: imiglucerase for injection	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase 3, Randomized, Multi-Center, Multi-National, Open-Label, Active Comparator Study to Evaluate the Efficacy and Safety of Genz-112638 in Patients With Gaucher Disease Type 1 Who Have Reached Therapeutic Goals With Enzyme Replacement Therapy

Resource links provided by NLM:

Genetics Home Reference related topics: Chanarin-Dorfman syndrome cholesteryl ester storage disease succinic semialdehyde dehydrogenase deficiency

MedlinePlus related topics: Gaucher's Disease

Drug Information available for: Alglucerase Imiglucerase

U.S. FDA Resources

Further study details as provided by Genzyme:

Primary Outcome Measures:

The percentage of patients who remain stable for 52 weeks (the primary analysis period) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Absolute change in total T- and Z-scores for bone mineral density from baseline to week 52 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Absolute change in hemoglobin levels (g/dL) from baseline to week 52 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Percent change in platelet counts from baseline to week 52 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Percent change in spleen volume (in multiples of normal (MN)) from baseline to week 52 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Percent change in liver volume (in MN) from baseline to week 52 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

Enrollment:	160
Study Start Date:	September 2009
Estimated Study Completion Date:	March 2015
Estimated Primary Completion Date:	November 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Investigational eliglustat tartrate (Genz-112638)	Drug: eliglustat tartrate Capsules: 50, 100, or 150 mg BID (twice daily) Other Name: Genz-112638
Active Comparator: imiglucerase for injection	Drug: imiglucerase for injection Intravenous (IV) Infusion, Varied Dose, Q2(bi-weekly) Other Name: Cerezyme

Detailed Description:

Gaucher disease is characterized by lysosomal accumulation of glucosylceramide due to impaired glucosylceramide hydrolysis. Gaucher disease type 1, which is the most common form, accounts for >90% of cases and does not involve the CNS. Typical manifestations of Gaucher disease type 1 include splenomegaly, hepatomegaly, thrombocytopenia, anemia, bone disease, and decreased quality of life. The disease manifestations are caused by the accumulation of glucosylceramide (storage material) in macrophages (called Gaucher cells) which have infiltrated the spleen and liver as well as other tissues.

Eliglustat tartrate (Genz-112638) is a small molecule drug 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 with Gaucher disease type 1 who have been stabilized on enzyme replacement therapy.

Eligibility

Ages Eligible for Study:	18 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 18 years old at the time of randomization.
The patient has a confirmed diagnosis of Gaucher disease type 1.
The patient has received treatment with enzyme replacement therapy (ERT) for at least 3 years. Within the 9 months prior to randomization, the patient has received a total monthly dose of 30 to 130 U/kg for at least 6 months.
The patient has reached Gaucher disease therapeutic goals prior to randomization.
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 within 3 years prior to randomization.
The patient has received substrate reduction therapies for Gaucher disease within 6 months prior to randomization.
The patient has Gaucher disease type 2 or 3 or is suspected of having Gaucher disease type 3.
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 illnesses that may confound the study results or, in 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: NCT00943111

Show 35 Study Locations

Sponsors and Collaborators

Genzyme

Investigators

Study Director:

Medical Monitor

Genzyme

More Information

Additional Information:

A phase 2 study of eliglustat tartrate (Genz-112638), an oral substrate reduction therapy for Gaucher disease type 1 This link exits the ClinicalTrials.gov site

This link exits the ClinicalTrials.gov site

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.

Responsible Party:	Genzyme
ClinicalTrials.gov Identifier:	NCT00943111 History of Changes
Other Study ID Numbers:	GZGD02607, 2008-005223-28
Study First Received:	July 20, 2009
Last Updated:	April 24, 2012
Health Authority:	United States: Food and Drug Administration Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica Australia: Department of Health and Ageing Therapeutic Goods Administration Brazil: Ministry of Health Canada: Health Canada Czech Republic: State Institute for Drug Control Egypt: Ministry of Health and Population France: Ministry of Health Germany: Ministry of Health Italy: Ministry of Health Netherlands: Medicines Evaluation Board (MEB) Russia: Ministry of Health and Social Development of the Russian Federation Spain: Ministry of Health Turkey: Ministry of Health United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Genzyme:

Gaucher disease,
Genz-112638,
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 23, 2012