A Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease Who Have Reached Therapeutic Goals With Enzyme Replacement Therapy (ENCORE)
- Conditions
- Gaucher Disease, Type 1
- Interventions
- Registration Number
- NCT00943111
- Lead Sponsor
- Genzyme, a Sanofi Company
- Brief Summary
This Phase 3 study was designed to confirm the efficacy and safety of eliglustat tartrate (Genz-112638) in participants with Gaucher disease type 1 who had reached therapeutic goals with enzyme replacement therapy (ERT).
- 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 greater than (\>) 90% of cases and does not involve the central nervous system (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 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 was designed to determine the efficacy, safety, and PK of eliglustat tartrate in adult participants with Gaucher disease type 1 who had been stabilized on ERT.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 160
- 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 18 years old at the time of randomization
- The participant had a confirmed diagnosis of Gaucher disease type 1
- The participant had received treatment with ERT for at least 3 years. Within the 9 months prior to randomization, the participant had received a total monthly dose of 30 to 130 Units/kilogram for at least 6 months
- The participant had reached Gaucher disease therapeutic goals prior to randomization
- Female participants of childbearing potential must have 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
- The participant had a partial or total splenectomy within 3 years prior to randomization
- The participant had received substrate reduction therapies for Gaucher disease within 6 months prior to randomization
- The participant had Gaucher disease type 2 or 3 or was suspected of having Gaucher disease type 3
- The participant had 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 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Investigational Eliglustat tartrate Eliglustat tartrate Imiglucerase Imiglucerase -
- Primary Outcome Measures
Name Time Method Percentage of Participants Who Remained Stable for 52 Weeks During the Primary Analysis Period Baseline up to Week 52 For a participant to be classified as stable, the participant must have remained stable in hematological parameters (hemoglobin levels and platelet counts) and organ volumes (spleen, when applicable, and liver volumes in multiples of normal \[MN\]). Stable hematological parameters were defined as hemoglobin level did not decrease more than (\>) 1.5 gram per deciliter (g/dL) from baseline and platelet count did not decrease \>25% from baseline. Stable organ volumes were defined as spleen volume (in MN) did not increase \>25% from baseline, if applicable, and liver volume (in MN) did not increase \>20% from baseline.
Percentage of Participants Who Remained Stable Annually for 4 Years During the LTTP Week 52 up to week 208 For a participant to be classified as stable, the participant must have remained stable in hematological parameters (hemoglobin levels and platelet counts) and organ volumes (spleen, when applicable, and liver volumes in MN). Stable hematological parameters were defined as hemoglobin level did not decrease \>1.5 g/dL from baseline and platelet count did not decrease \>25% from baseline. Stable organ volumes were defined as spleen volume (in MN) did not increase \>25% from baseline, if applicable, and liver volume did not increase \>20% from baseline.
- Secondary Outcome Measures
Name Time Method Total T-Scores for Bone Mineral Density Baseline Images of the spine and bilateral femur were obtained by dual energy X-Ray absorptiometry (DXA) to determine T-score for each bone area and total bone mineral density. T-score compares participant's bone density with that of healthy young participant. The T-score bone density categories are: normal (score greater than \[\>\]-1), osteopenia (score -2.5 to less than or equal to \[\<=\] -1), and osteoporosis (score \<= -2.5).
Absolute Change From Baseline in Total T-Scores for Bone Mineral Density at Week 52 Baseline, Week 52 Images of the spine and bilateral femur were obtained by DXA to determine T-score for each bone area and total bone mineral density. T-score compares participant's bone density with that of healthy young participant. The T-score bone density categories are: normal (score \>-1), osteopenia (score -2.5 to \<=-1), and osteoporosis (score \<= -2.5). Absolute change = T-score at Week 52 minus T-score at baseline.
Total Z-Scores for Bone Mineral Density Baseline Images of the spine and bilateral 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 Total Z-Scores for Bone Mineral Density at Week 52 Baseline, Week 52 Images of the spine and bilateral 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 = Z-score at Week 52 minus Z-score at baseline.
Hemoglobin Level Baseline Absolute Change From Baseline in Hemoglobin Levels at Week 52 Baseline, Week 52 Absolute change = hemoglobin level at Week 52 minus hemoglobin level at baseline.
Percent Change From Baseline in Platelet Counts at Week 52 Baseline, Week 52 Percent change in platelet counts = (\[platelet count at Week 52 minus platelet count at baseline\] divided by \[platelet count at baseline\]) multiplied by 100.
Percent Change From Baseline in Spleen Volume (MN) at Week 52 Baseline, Week 52 Percent change in spleen volume = (\[spleen volume at Week 52 minus spleen volume at baseline\] divided by \[spleen volume at baseline\]) multiplied by 100, where all volumes are in MN.
Percent Change From Baseline in Liver Volume (in MN) at Week 52 Baseline, Week 52 Percent change in liver volume = (\[liver volume at Week 52 minus liver volume at baseline\] divided by \[liver volume at baseline\]) multiplied by 100, where all volumes are in multiples of normal.
Absolute Change From Baseline in Total T-Scores for Bone Mineral Density at Week 208 Baseline, Week 208 Images of the spine and bilateral femur were obtained by DXA to determine T-score for each bone area and total bone mineral density. T-score compares participant's bone density with that of healthy young participant. The T-score bone density categories are: normal (score \>-1), osteopenia (score -2.5 to \<=-1), and osteoporosis (score \<= -2.5). Absolute change = T-score at Week 208 minus T-score at baseline.
Absolute Change From Baseline in Total Z-Scores for Bone Mineral Density at Week 208 Baseline, Week 208 Images of the spine and bilateral 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 = Z-score at Week 208 minus Z-score at baseline.
Absolute Change From Baseline in Hemoglobin Levels at Week 208 Baseline, Week 208 Absolute change = hemoglobin level at Week 208 minus hemoglobin level at baseline.
Percent Change From Baseline in Platelet Counts at Week 208 Baseline, Week 208 Percent change in platelet counts = (\[platelet count at Week 208 minus platelet count at baseline\] divided by \[platelet count at baseline\]) multiplied by 100.
Percent Change From Baseline in Spleen Volume (in MN) at Week 208 Baseline, Week 208 Percent change in spleen volume = (\[spleen volume at Week 208 minus spleen volume at baseline\] divided by \[spleen volume at baseline\]) multiplied by 100, where all volumes are in MN.
Percent Change From Baseline in Liver Volume (in MN) at Week 208 Baseline, Week 208 Percent change in liver volume = (\[liver volume at Week 208 minus liver volume at baseline\] divided by \[liver volume at baseline\]) multiplied by 100, where all volumes are in multiples of normal.
Trial Locations
- Locations (34)
Albany Medical Center
🇺🇸Albany, New York, United States
North Shore University Medical Center
🇺🇸Manhasset, New York, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Tower Hematology Oncology Medical Group
🇺🇸Beverly Hills, California, United States
UCSF MS Center
🇺🇸San Francisco, California, United States
University of Colorado Health Science Center - Aurora
🇺🇸Aurora, Colorado, United States
Emory University Medical Genetics
🇺🇸Decatur, Georgia, United States
Children's Memorial Hospital
🇺🇸Chicago, Illinois, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Northwest Oncology Hematology Associates PA
🇺🇸Coral Springs, Florida, United States
New York University School of Medicine
🇺🇸New York, New York, United States
Mount Sinai School of Medicine
🇺🇸New York, New York, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
O and O Alpan LLC
🇺🇸Springfield, Virginia, United States
Royal Perth Hospital
🇦🇺Perth, WA, Australia
Hospital General de Agudos J.M Ramos Mejia
🇦🇷Buenos Aires, Argentina
Hospital General de Ninos Dr. Ricardo Gutierrez
🇦🇷Buenos Aires, Argentina
Hospital de Clinicas da Universidade Federal do Parana
🇧🇷Curitiba, Brazil
IGEIM
🇧🇷São Paulo, Brazil
Mount Sinai Hospital and the Samuel Lunenfeld Research Institute
🇨🇦Toronto Ontario, Canada
Abou El Reesh Children's University Hospital (El Mounira), Faculty of Medicine (Kasr Al-Aini), Cairo University Hospitals, El Mounira, Cairo, Egypt
🇪🇬Cairo, Egypt
Hôpital Beaujon
🇫🇷Clichy, France
Katholische Kliniken Oberhausen gem. GmbH
🇩🇪Oberhausen, Germany
Charité Universitätsmedizin Berlin
🇩🇪Berlin, Germany
Asklepios Klinik St. Georg
🇩🇪Hamburg, Germany
Azienda Ospedialiero-Universitaria S. Maria Della Misericordia
🇮🇹Udine, Italy
Azienda Ospedaliero Universitaria Careggi
🇮🇹Firenze, Italy
Hospital University Miguel Servet
🇪🇸Zaragoza, Spain
Hematology Research Center of Ministry of Healthcare of the Russian Federation
🇷🇺Moscow, Russian Federation
Cambridge University Hosptials, Addenbrookes Hospital
🇬🇧Cambridge, United Kingdom
Yale University School of Medicine
🇺🇸New Haven, Connecticut, United States
Instituto de Estadual de Hematologia Arthur de Siqueria Cavalcanti
🇧🇷Rio de Janeiro, Brazil