Phase 2
N=26
A Study of the Efficacy and Safety of Eliglustat Tartrate (Genz-112638) in Type 1 Gaucher Patients
Gaucher Disease, Type 1 · Cerebroside Lipidosis Syndrome · Glucocerebrosidase Deficiency Disease · Glucosylceramide Beta-Glucosidase Deficiency Disease · Gaucher Disease, Non-Neuronopathic Form
Bottom Line
View on ClinicalTrials.gov: NCT00358150 ↗Enrolled (actual)
26
Serious AEs
16.3%
Results posted
Sep 2014
Primary outcome: Primary: Percentage of Participants Demonstrating A Meaningful Clinical Response — 77 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Eliglustat tartrate (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Genzyme, a Sanofi Company
- Primary completion
- Aug 2009
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Demonstrating A Meaningful Clinical Response |
77 | — |
| SECONDARY Percent Change From Baseline in Spleen Volume at Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study |
-38.5; -52.4; -59.1; -62.5; -63.9; -66.2 | — |
| SECONDARY Percent Change From Baseline in Liver Volume at Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study |
-16.9; -23.9; -26.8; -28.0; -31.2; -28.4 | — |
| SECONDARY Absolute Change From Baseline in Hemoglobin at Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study |
1.70; 2.13; 2.47; 2.27; 2.09; 2.01 | — |
| SECONDARY Percent Change From Baseline in Platelet Count at Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study |
41.3; 81.5; 87.9; 95.1; 90.9; 114.3 | — |
| SECONDARY Percent Change From Baseline in Biomarker (Angiotensin Converting Enzyme) Level at Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study |
-35.1; -53.5; -56.7; -60.7; -55.7; -61.5 | — |
| SECONDARY Percent Change From Baseline in Biomarker (Tartrate-Resistant Acid Phosphatase [TRAP]) Level at Year 1 and Year 2 |
-37.0; -52.5 | — |
| SECONDARY Percent Change From Baseline in Biomarker Chemokine Ligand 18 (CCL18) Level at Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and End of Study |
-49.0; -72.1; -68.6; -80.2; -89.4; -82.7 | — |
| SECONDARY Percent Change From Baseline in Biomarker (Chitotriosidase) Level at Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study |
-49.9; -73.5; -76.4; -79.2; -76.7; -74.1 | — |
| SECONDARY Change From Baseline in 36-Item Short Form (SF-36) Health Survey Scores at Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8 and Year 9 at End of Study |
8.41; 9.50; 12.65; 11.32; 10.76; 12.63 | — |
| SECONDARY Change From Baseline in Fatigue Severity Scale (FSS) Scores at Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study |
-0.56; -0.63; -1.37; -1.41; -1.26; -1.21 | — |
| SECONDARY Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study |
23; 17; 17; 14; 14; 16 | — |
| SECONDARY Number of Participants With Mobility Status (MS) at Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study |
24; 22; 20; 19; 19; 19 | — |
| SECONDARY Number of Participants With No Bone Crisis at Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study |
26; 22; 20; 19; 19; 19 | — |
| SECONDARY Bone Marrow Infiltration: Number of Participants With Improvement From Baseline in Dark Marrow at Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8 and at End of Study (EOS) |
3; 2; 2; 2; 4; 5 | — |
| SECONDARY Lumbar Spine and Femur T-Scores for Bone Mineral Density (BMD) at Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study |
-1.85; -1.43; -0.93; -1.09; -0.88; -0.79 | — |
| SECONDARY Lumbar Spine and Femur Z-Scores for BMD at Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study |
-1.49; -1.11; -0.64; -0.63; -0.48; -0.37 | — |
Summary
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.
Eligibility Criteria
Inclusion Criteria
- The participant had a diagnosis of Gaucher Type I disease and a documented deficiency of glucocerebrosidase activity by enzyme assay and was willing and able to provide written informed consent prior to initiating any study-related procedures;
- The participant was 18 to 65 years old and weighed between 50 and 120 kilogram (kg) at enrollment;
- The participant had 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 had a documented negative serum pregnancy test prior to dosing. Female participants agreed to use a reliable method of birth control throughout duration of trial.
Exclusion Criteria
- Participant had a partial or total splenectomy or infarcted areas of the spleen;
- Participant had documented prior bleeding varices or liver infarction;
- Participant received miglustat within 12 months prior to study enrollment;
- The participant had received an investigational product within 30 days prior to study enrollment;
- Participant had neurologic or pulmonary involvement;
- Participant had new pathological bone involvement or bone crisis in the 12 months prior to enrollment;
- Participant was transfusion-dependent;
- Participant had a documented etiology of anemia due to causes other than Gaucher disease;
- The participant had cardiac functional and/or anatomical abnormalities, a history of cancer or tested positive for human immunodeficiency virus (HIV) antibody or Hepatitis;
- Participant had 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, might preclude participation in the study.
Data sourced from ClinicalTrials.gov (NCT00358150). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.