A Study of the Efficacy and Safety of Eliglustat Tartrate (Genz-112638) in Type 1 Gaucher Patients

This study has been completed.
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier:
First received: July 27, 2006
Last updated: June 16, 2016
Last verified: June 2016

Gaucher disease is a genetic disease that results in a deficiency of an enzyme acid beta-glucosidase, also known as glucocerebrosidase. This enzyme is needed to digest a substrate (lipid) called glucosylceramide and, to a lesser degree, glucosylsphingosine. In participants with Gaucher disease, the liver, spleen, bone marrow and brain show increases in lipid concentration, specifically in cells derived from the monocyte/macrophage system.

Eliglustat tartrate (Genz-112638) is an oral drug that may regulate the Gaucher disease process by decreasing the synthesis of glucosylceramide. The primary objective of this study is to evaluate the efficacy, safety and pharmacokinetics (PK) of eliglustat tartrate, administered as an oral dose of either 50 milligram (mg) twice daily (BID) or 100 mg BID, to men and women with Gaucher disease Type 1 for 52 weeks.

Condition Intervention Phase
Gaucher Disease, Type 1
Cerebroside Lipidosis Syndrome
Glucocerebrosidase Deficiency Disease
Glucosylceramide Beta-Glucosidase Deficiency Disease
Gaucher Disease, Non-Neuronopathic Form
Drug: Eliglustat tartrate
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Open-Label, Multi-Center Study Evaluating the Efficacy, Safety and Pharmacokinetics of Genz-112638 in Gaucher Type 1 Patients

Resource links provided by NLM:

Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Percentage of Participants Demonstrating A Meaningful Clinical Response [ Time Frame: Baseline, Week 52 ]
    A meaningful clinical response was defined as an improvement in at least 2 of the 3 main efficacy parameters: a) an increase in hemoglobin of greater than or equal to (>=) 0.5 gram/deciliter from baseline, b) an increase in platelets of >=15 percent (%) from baseline, c) reduction in total spleen volume of >= 15% from baseline. As hemoglobin, platelets, total spleen volume were abnormal at baseline, within each participant, only those parameters were used in the evaluation of meaningful clinical response which were abnormal at baseline.

Secondary Outcome Measures:
  • Percent Change From Baseline in Spleen Volume at Month 48 [ Time Frame: Baseline, Month 48 ]
    Percent change in spleen volume = ([spleen volume at Month 48 minus spleen volume at baseline] divided by [spleen volume at baseline]) multiplied by 100, where all volumes are in multiples of normal.

  • Percent Change From Baseline in Liver Volume at Month 48 [ Time Frame: Baseline, Month 48 ]
    Percent change in liver volume = ([liver volume at Month 48 minus liver volume at baseline] divided by [liver volume at baseline]) multiplied by 100, where all volumes are in multiples of normal.

  • Absolute Change From Baseline in Hemoglobin at Month 48 [ Time Frame: Baseline, Month 48 ]
    Absolute change = hemoglobin level at Month 48 minus hemoglobin level at baseline.

  • Percent Change From Baseline in Platelet Count at Month 48 [ Time Frame: Baseline, Month 48 ]
    Percent change in platelet count = ([platelet count at Month 48 minus platelet count at baseline] divided by [platelet count at baseline]) multiplied by 100.

Other Outcome Measures:
  • Change From Baseline in Biomarkers (Angiotensin Converting Enzyme [ACE], Tartrate-Resistant Acid Phosphatase [TRAP], Chemokine Ligand 18 [CCL18], Chitotriosidase) at Month 48 [ Time Frame: Baseline, Month 48 ]
  • Participant Reported Quality of Life: Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey at Month 48 [ Time Frame: Baseline, Month 48 ]
  • Participant Reported Quality of Life: Fatigue Severity Scale Survey at Month 48 [ Time Frame: Baseline, Month 48 ]
  • Change From Baseline in Mobility, Bone Pain, and Bone Crisis at Month 48 [ Time Frame: Baseline, Month 48 ]
  • Change From Baseline in Radiographic Measures of Bone Disease at Month 48 [ Time Frame: Baseline, Month 48 ]

Enrollment: 26
Study Start Date: June 2006
Study Completion Date: December 2015
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Eliglustat tartrate Drug: Eliglustat tartrate
Eliglustat (Genz-112638) capsule as single 50 milligram (mg) dose on Day 1 then eliglustat 50 mg twice daily (BID) from Day 2 to Day 19, and then either eliglustat 50 mg BID (if Genz-99067 [active moiety of eliglustat in plasma] trough plasma concentration was greater than or equal to [>=] 5 nanogram per milliliter [ng/mL] on Day 10) or eliglustat 100 mg BID (if Genz-99067 trough plasma concentration was less than [<] 5 ng/mL), from day 20 to Month 48. After primary completion date (Week 52) participants underwent treatment interruption period of approximately 2 weeks before continuing the same treatment up to Month 48. Participant receiving 100 mg BID could be considered for a further dose increase to 150 mg BID at Week 24 if they met certain criteria (for example, had been on treatment for at least 24 months, had not reached therapeutic goals established for participants receiving Cerezyme), and if all other causes for lack of treatment effect had been evaluated and ruled out).
Other Name: Genz-112638

Detailed Description:
This study consists of several phases: screening (-28 to -1 days), dose adjustment/treatment (Day 1 [treatment baseline] to Day 30), initial steady-state treatment (post-Day 30 through Week 52 post-baseline), a treatment interruption period (Week 52 through approximately Week 54), long-term steady-state treatment (approximately Week 54 through study completion), and safety follow-up (30 to 37 days after a participant withdraws from or completes the study). The Primary Analysis Period is from baseline through Week 52. The Extension Period is from Week 52 through study completion (that is, participant withdrawal, the study is terminated, eliglustat tartrate becomes commercially available, or where applicable, specific regulatory requirements have been met).

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • The participant has a diagnosis of Gaucher Type I disease and a documented deficiency of glucocerebrosidase activity by enzyme assay and is willing and able to provide written informed consent prior to initiating any study-related procedures
  • The participant is 18 to 65 years old and weighs between 50 and 120 kilogram (kg) at enrollment
  • The participant has the following symptoms of Gaucher disease identified within 28 days of enrollment (at screening):

    • Anemia - indicated by hemoglobin measurements taken during the screening phase (8 to 10 gram per deciliter (g/dL) if female, 8 to 11 g/dL if male)
    • Thrombocytopenia - indicated by platelet count measurements taken during the screening phase (60000 to 100000 per cubic millimeter)
    • Splenomegaly, as indicated by magnetic resonance imaging (MRI) or spiral computed tomography (CT) (>= 10 multiples of normal)
  • Female participants of child-bearing potential must have a documented negative serum pregnancy test prior to dosing. Female participants agree to use a reliable method of birth control throughout duration of trial

Exclusion Criteria:

  • Participant has had a partial or total splenectomy or infarcted areas of the spleen
  • Participant has documented prior bleeding varices or liver infarction
  • Participant received miglustat within 12 months prior to study enrollment
  • The participant has received an investigational product within 30 days prior to study enrollment
  • Participant has neurologic or pulmonary involvement
  • Participant has new pathological bone involvement or bone crisis in the 12 months prior to enrollment
  • Participant is transfusion-dependent
  • Participant has a documented etiology of anemia due to causes other than Gaucher disease
  • The participant has cardiac functional and/or anatomical abnormalities, a history of cancer or tested positive for human immunodeficiency virus (HIV) antibody or Hepatitis
  • Participant has a clinically significant disease, other than Gaucher disease, including cardiovascular, renal, hepatic, gastrointestinal, pulmonary, neurologic, endocrine, metabolic, or psychiatric disease, other medical conditions, or serious intercurrent illnesses that, in the opinion of the Investigator, may preclude participation in the study
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00358150

United States, New York
New York University
New York, New York, United States
New York, New York, United States
Aprillus Asistencia e Investigación
Buenos Aires, Argentina
Hospital de Oncologia Maria Curie
Buenos Aires, Argentina
Buenos Aires, Argentina
Instituto Argentino de Diagnostico y Tratamiento (IADT)
Buenos Aires, Argentina
Buenos Aires, Argentina
Hospital Ramos Mejia
Ciudad Autonoma de Buenos Aires, Argentina
Rambam Medical Center
Haifa, Israel
Haifa, Israel
Sha'are Zedek Medical Centre
Jerusalem, Israel
Jerusalem, Israel
Universita degli Studi di Milano
Milano, Italy
Instituto Mexicano del Seguro Social
D.f., Mexico
Mexico City, Mexico
Russian Federation
Hematology Research Center of Ministry of Healthcare of the Russian Federation
Moscow, Russian Federation
Moscow, Russian Federation
Sponsors and Collaborators
Genzyme, a Sanofi Company
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information


Responsible Party: Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier: NCT00358150     History of Changes
Other Study ID Numbers: GZGD00304  2005-004732-42  DRI12816 
Study First Received: July 27, 2006
Results First Received: August 22, 2014
Last Updated: June 16, 2016

Keywords provided by Sanofi:
Type 1 Gaucher Disease
Glucocerebrosidase Deficiency Disease

Additional relevant MeSH terms:
Gaucher Disease
Deficiency Diseases
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
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders
Nutrition Disorders
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on January 19, 2017