A Study of the Efficacy and Safety of Eliglustat Tartrate (Genz-112638) in Type 1 Gaucher Patients
- Conditions
- Gaucher Disease, Non-Neuronopathic FormGlucocerebrosidase Deficiency DiseaseGaucher Disease, Type 1Cerebroside Lipidosis SyndromeGlucosylceramide Beta-Glucosidase Deficiency Disease
- Interventions
- Registration Number
- NCT00358150
- Lead Sponsor
- Genzyme, a Sanofi Company
- Brief 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.
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 26
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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;
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The participant was 18 to 65 years old and weighed between 50 and 120 kilogram (kg) at enrollment;
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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);
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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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Eliglustat tartrate Eliglustat tartrate -
- Primary Outcome Measures
Name Time Method Percentage of Participants Demonstrating A Meaningful Clinical Response Baseline, Year 1 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
Name Time Method 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 Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (Up to Year 9) Percent change in spleen volume = (\[spleen volume at specified time points minus spleen volume at baseline\] 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 Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (Up to Year 9) Percent change in liver volume = (\[liver volume at specified time points minus liver volume at baseline\] divided by \[liver volume at baseline\]) multiplied by 100, where all volumes are in multiples of normal.
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 Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (Up to Year 9) Percent change in platelet count = (\[platelet count at specified time points minus platelet count at baseline\] divided by \[platelet count at baseline\]) multiplied by 100.
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 Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and End of Study (Up to Year 9) 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 Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (Up to Year 9) 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) Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8 and at End of Study (up to Year 9) Bone marrow infiltration assessments were designed to evaluate improvements in dark marrow using MRI. Each MRI assessment was performed for both femurs and consisted of reviewing 6 different zones (the femoral head, greater trochanter, intertrochanteric region, shaft, distal metaphysis, and condyles). MRI images recorded dark marrow for each zone as either present or not present at baseline. In this outcome, number of participants (for whom dark marrow was present at baseline) with improvement from baseline in dark marrow at each specified time point were reported.
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 Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (up to Year 9) Images of the lumbar spine and femur were obtained by DXA to determine Z-score for each bone area and total bone mineral density. The Z-score bone density categories are: normal (score \>-2) and below normal (score \<=-2).
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 Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (Up to Year 9) Absolute change = hemoglobin level at specified time points minus hemoglobin level at baseline.
Percent Change From Baseline in Biomarker (Tartrate-Resistant Acid Phosphatase [TRAP]) Level at Year 1 and Year 2 Baseline, Year 1, Year 2 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 Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and End of Study (Up to Year 9) 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 Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (Up to Year 9) The SF-36 questionnaire, version 2, investigates the participant's health-related quality of life (HRQL). It is a 36-item questionnaire measuring 8 domains (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Each domain score ranges from 0 (worst) to 100 (best), with higher scores reflecting best health-related quality of life. Two summary scale scores were computed from the 8 domain scores: the Physical Component Summary and the Mental Component Summary. Score range for both summary scale ranges from 0 (worst) to 100 (best), with higher scores reflecting best health-related quality of life.
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 Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (Up to Year 9) The FSS is an instrument consisting of 9 self-administered questions that measures the impact of severity of fatigue symptoms on everyday functioning, based on the recall over the past week. Score range for each question ranges from 1 (minimum) to 7 (maximum), where higher score indicates greater severity. FSS total score was calculated by averaging the results of all questions. Total FSS score ranges from 9 (minimum) to 63 (maximum), where higher scores indicates greater severity.
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 Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (Up to Year 9) Bone pain was assessed as a part of Gaucher disease assessment in participants. Participants were categorized as none (no bone pain), very mild bone pain, mild bone pain and moderate bone pain. In this outcome, number of participants with different levels of bone pain at specified time points were reported.
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 Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (Up to Year 9) Mobillity, i.e. ability to walk was assessed as a part of Gaucher disease assessment in participants.In this outcome, number of participants with their different mobility status (unrestricted mobility, walks with difficulty) at specified time points were reported.
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 Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (Up to Year 9) Bone crisis was assessed as a part of Gaucher disease assessment in participants. Acute, excruciating episodic bone pain is characteristic of Gaucher bone crisis, which typically causes debilitation lasting several days or longer and requires treatment with immobilization, hydration, and opioid analgesics. Participants were categorized as 0= no bone crisis, 1= 1 bone crisis, and 2= 2 bone crises during the assessment period. In this outcome, number of participants with 0= no bone crises levels at specified time points were reported.
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 Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (up to Year 9) Images of the lumbar spine and femur were obtained by dual energy X-ray absorptiometry (DXA) to determine T-score for each bone area and total bone mineral density. T-scores compares participant's bone density with that of healthy young participant of same gender. The T-score bone density categories were: normal (score \>-1), osteopenia (score -2.5 to \<=-1), and osteoporosis (score \<= -2.5).
Trial Locations
- Locations (11)
New York University
🇺🇸New York, New York, United States
IMAI
🇦🇷Buenos Aires, Argentina
Rambam Medical Center
🇮🇱Haifa, Israel
Universita degli Studi di Milano
🇮🇹Milano, Italy
Hospital Ramos Mejia
🇦🇷Ciudad Autonoma de Buenos Aires, Argentina
Hematology Research Center of Ministry of Healthcare of the Russian Federation
🇷🇺Moscow, Russian Federation
Instituto Mexicano del Seguro Social
🇲🇽D.f., Mexico
Aprillus Asistencia e Investigación
🇦🇷Buenos Aires, Argentina
Hospital de Oncologia Maria Curie
🇦🇷Buenos Aires, Argentina
Instituto Argentino de Diagnostico y Tratamiento (IADT)
🇦🇷Buenos Aires, Argentina
Sha'are Zedek Medical Centre
🇮🇱Jerusalem, Israel