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Trial record 7 of 11 for:    eliglustat

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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00891202
First Posted: May 1, 2009
Last Update Posted: March 3, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )
  Purpose
This Phase 3 study was designed to confirm the efficacy and safety of eliglustat tartrate (Genz-112638) in participants 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
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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 (ENGAGE)

Resource links provided by NLM:


Further study details as provided by Sanofi ( Genzyme, a Sanofi Company ):

Primary Outcome Measures:
  • PAP: Percent Change From Baseline in Spleen Volume (in Multiples of Normal [MN]) at Week 39 of the Primary Analysis Period With Eliglustat Tartrate Treatment as Compared to Placebo [ Time Frame: PAP Baseline (Day 1), Week 39 ]
    Percent change in spleen volume = ([spleen volume at Week 39 minus spleen volume at baseline] divided by [spleen volume at baseline]) multiplied by 100, where all volumes are in MN.


Secondary Outcome Measures:
  • PAP: Hemoglobin Level [ Time Frame: PAP Baseline (Day 1) ]
  • PAP: Absolute Change From Baseline in Hemoglobin Level at Week 39 [ Time Frame: PAP Baseline (Day 1), Week 39 ]
    Absolute change = hemoglobin level at Week 39 minus hemoglobin level at baseline.

  • PAP: Percent Change From Baseline in Liver Volume (in MN) at Week 39 [ Time Frame: PAP Baseline (Day 1), Week 39 ]
    Percent change in liver volume = ([liver volume at Week 39 minus liver volume at baseline] divided by [liver volume at baseline]) multiplied by 100, where all volumes are in MN.

  • PAP: Percent Change From Baseline in Platelet Counts at Week 39 [ Time Frame: PAP Baseline (Day 1), Week 39 ]
    Percent change in platelet count = ([platelet count at Week 39 minus platelet count at baseline] divided by [platelet count at baseline]) multiplied by 100.

  • LTTP: Percent Change From Baseline in Spleen Volume (in MN) at Week 234 [ Time Frame: PAP Baseline for Eliglustat (Originally on Eliglustat) arm, LTTP Baseline for Eliglustat (Originally on Placebo) arm, Week 234 ]
    Percent change in spleen volume = ([spleen volume at Week 234 minus spleen volume at baseline] divided by [spleen volume at baseline]) multiplied by 100, where all volumes are in MN. Baseline values for the original placebo participants refer to Day 1 of LTTP and baseline values for the original eliglustat participants refer to the Day 1 of PAP.

  • LTTP: Absolute Change From Baseline in Hemoglobin Level at Week 234 [ Time Frame: PAP Baseline for Eliglustat (Originally on Eliglustat) arm, LTTP Baseline for Eliglustat (Originally on Placebo) arm, Week 234 ]
    Baseline values for the original placebo participants refer to Day 1 of LTTP and baseline values for the original eliglustat participants refer to the Day 1 of PAP.

  • LTTP: Percent Change From Baseline in Liver Volume (in MN) at Week 234 [ Time Frame: PAP Baseline for Eliglustat (Originally on Eliglustat) arm, LTTP Baseline for Eliglustat (Originally on Placebo) arm, Week 234 ]
    Percent change in liver volume = ([liver volume at Week 234 minus liver volume at baseline] divided by [liver volume at baseline]) multiplied by 100, where all volumes are in MN. Baseline values for the original placebo participants refer to Day 1 of LTTP and baseline values for the original eliglustat participants refer to the Day 1 of PAP.

  • LTTP: Percent Change From Baseline in Platelet Counts at Week 234 [ Time Frame: PAP Baseline for Eliglustat (Originally on Eliglustat) arm, LTTP Baseline for Eliglustat (Originally on Placebo) arm, Week 234 ]
    Percent change in platelet count = ([platelet count at Week 234 minus platelet count at baseline] divided by [platelet count at baseline]) multiplied by 100. Baseline values for the original placebo participants refer to Day 1 of LTTP and baseline values for the original eliglustat participants refer to the Day 1 of PAP.


Enrollment: 40
Study Start Date: November 2009
Study Completion Date: January 2016
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Active
Eliglustat
Drug: Eliglustat tartrate
PAP: Eliglustat tartrate (ET) capsule 50 mg orally on Day 1 followed by ET 50 mg capsule twice daily (BID) from Day 2 to Week 4, then either ET 50 mg capsule BID (participants with Genz-99067 [active moiety of ET in plasma] trough plasma concentration >=5 ng/mL) or ET 100 mg capsule BID (participants with Genz-99067 trough plasma concentration <5 ng/mL), up to Week 39. PK assessment at Week 2 used for dose adjustment after Week 4. LTTP: Participants of the eliglustat arm in PAP who completed PAP were included in LTTP and received ET capsule 50 mg BID orally from Day 1 (post Week 39) until Week 43 followed by ET 50 mg or 100 mg capsule BID up to Week 47, then ET 50 mg or 100 mg or 150 mg capsule BID up to Week 312. Dose adjustments at Week 43 and Week 47 were based on Genz-99067 trough plasma concentrations (if trough plasma concentration <5 ng/mL: next higher dose administered; if >=5 ng/mL: same dose continued) at Week 41 & Week 45, respectively.
Other Name: Genz-112638
Placebo Comparator: Placebo
Placebo
Drug: Placebo
PAP: Matching placebo capsule once daily on Day 1 followed by matching placebo capsule BID from Day 2 through Week 39. LTTP: Participants of the placebo arm in PAP who completed PAP were included in LTTP and received eliglustat tartrate from Day 1 (post Week 39) up to Week 312. Day 1 (post Week 39) was considered as baseline for LTTP. On Day 1, participants received eliglustat tartrate capsule 50 mg BID orally until Week 43 followed by eliglustat tartrate 50 mg or 100 mg capsule BID up to Week 47, then eliglustat tartrate 50 mg or 100 mg or 150 mg capsule BID up to Week 312. Dose adjustments at Week 43 and Week 47 were based on Genz-99067 trough plasma concentrations (if trough plasma concentration <5 ng/mL: next higher dose administered; if >=5 ng/mL: same dose continued) at Week 41 & Week 45, respectively.

Detailed Description:

Gaucher disease is characterized by lysosomal accumulation of glucosylceramide due to impaired glucosylceramide hydrolysis. Type 1 Gaucher disease, the most common form accounts for greater than (>) 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 is a small molecule developed as an oral therapy which acts to specifically inhibit production of this storage material in Gaucher cells.

This study was designed to determine the efficacy, safety, and pharmacokinetics (PK) of eliglustat tartrate in adult participants (>16 years) with Gaucher disease Type 1. The study consisted of 2 periods: The Double-Blind Primary Analysis Period (PAP [Day 1 to Week 39]) and the Long Term Treatment Period (LTTP/Open-Label Period (post-Week 39 [Day 1 of the Open-Label Period] through study completion).

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • The participant has had a partial or total splenectomy;
  • The participant had received pharmacological chaperones or miglustat within 6 months prior to randomization;
  • The participant had received enzyme replacement therapy within 9 months prior to randomization;
  • The participant had Type 2 or 3 Gaucher disease or was suspected of having Type 3 Gaucher disease;
  • The participant had any clinically significant disease, other than Gaucher disease, including cardiovascular, renal, hepatic, gastrointestinal (GI), pulmonary, neurologic, endocrine, metabolic, (for example, hypokalemia, hypomagnesemia), or psychiatric disease, other medical conditions, or serious intercurrent illness that might confound the study results, or, on the opinion of the investigator, might preclude participation in the study;
  • The participant had tested positive for the human immunodeficiency virus (HIV) antibody, Hepatitis C antibody, or Hepatitis B surface antigen;
  • The participant had received an investigational product within 30 days prior to randomization;
  • The participant was pregnant or lactating.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00891202


Locations
United States, California
UCSF MS Center
San Francisco, California, United States, 94143
United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06510
United States, Georgia
Emory University Medical Genetics
Decatur, Georgia, United States, 30033
United States, Kansas
University of Kansas Medical Center, Division of Hematology/Oncology, Dept. of Medicine
Westwood, Kansas, United States, 66160
United States, New York
New York University School of Medicine, Neurology Department
New York, New York, United States, 10016
Mount Sinai School of Medicine
New York, New York, United States, 10029
Bulgaria
University hospital "Alexandrovska" Sofia
Sofia, Bulgaria, 1431
Canada
Sir Mortimer B. Davis - Jewish General Hospital
Montreal, Quebec, Canada, H3T 1E2
Mount Sinai Hospital and the Samuel Lunenfeld Research Institute
Toronto Ontario, Canada, M5G 1X5
Colombia
Hospital de San Jose
Bogota, Colombia
India
Christian Medical College Hospital
Vellore, India, 632004
Israel
Rabin Medical Center, Beilinson Hospital
Petach Tikvah, Israel, 49100
Lebanon
Hôtel-Dieu de France University Hospital
Beirut, Lebanon
Mexico
OCA Hospital
Monterrey, Nuevo Leon, Mexico
Russian Federation
Hematology Research Center of Ministry of Healthcare of the Russian Federation
Moscow, Russian Federation, 125167
Serbia
Institut za endokrinologiju
Belgrade, Serbia, 11000
Tunisia
Hopital La-Rabta
Tunis, TN, Tunisia, 1007
United Kingdom
Royal Free Hospital
London, United Kingdom, NW3 2QG
Sponsors and Collaborators
Genzyme, a Sanofi Company
Investigators
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information

Publications:

Responsible Party: Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier: NCT00891202     History of Changes
Other Study ID Numbers: GZGD02507
2008-005222-37 ( EudraCT Number )
EFC12813 ( Other Identifier: Sanofi )
First Submitted: April 30, 2009
First Posted: May 1, 2009
Results First Submitted: August 22, 2014
Results First Posted: September 3, 2014
Last Update Posted: March 3, 2017
Last Verified: January 2017

Keywords provided by Sanofi ( Genzyme, a Sanofi Company ):
Gaucher,
beta-glucosidase,
acid ß-glucosidase,
glucocerebrosidase,
glucosylceramide,
D-glucosyl-N-acylsphingosine glucohydrolase,
substrate reduction therapy

Additional relevant MeSH terms:
Eliglustat
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
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action