A Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease Who Have Reached Therapeutic Goals With Enzyme Replacement Therapy (ENCORE)
NCT ID: NCT00943111
Last Updated: 2016-11-25
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
160 participants
INTERVENTIONAL
2009-09-30
2015-06-30
Brief Summary
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Detailed Description
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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.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Investigational
Eliglustat tartrate
Eliglustat tartrate
Primary analysis period (PAP): Eliglustat tartrate capsule 50 milligram (mg) twice daily (BID) orally from Day 1 to Week 4 followed by eliglustat tartrate 50 mg or 100 mg capsule BID up to Week 8, and then eliglustat tartrate 50 mg or 100 mg or 150 mg capsule BID up to Week 52. Dose adjustments after Week 4 and Week 8 were based on Genz-99067 (active moiety of eliglustat tartrate in plasma) trough plasma concentrations. If Genz-99067 trough plasma concentration was less than (\<) 5 nanogram per milliliter \[ng/mL\] next higher dose was administered whereas if Genz-99067 trough plasma concentration was greater than or equal to (\>=) 5 ng/mL same dose was continued. Pharmacokinetic (PK) assessment at Week 2 and 6 were used for dose adjustment after Week 4 and Week 8, respectively.
Long-term treatment period (LTTP): Participants originally randomized to eliglustat in PAP continued to receive eliglustat dose, based on their Genz 99067 plasma trough concentration at Week 6.
Imiglucerase
Imiglucerase
PAP: Imiglucerase intravenous infusion every other week (q2w) up to Week 52 in doses equivalent to participant's past ERT dose prior to any unanticipated treatment interruption, dose reduction, or regimen change.
LTTP: Participants originally randomized to imiglucerase received eliglustat tartrate capsule 50 mg BID orally from Week 52+1 Day to Week 56 followed by eliglustat tartrate 50 mg or 100 mg capsule BID up to Week 60, and then eliglustat tartrate 50 mg or 100 mg or 150 mg capsule BID up to 5 years. The dose adjustments after Week 56 and Week 60 were based on Genz-99067 (active moiety of eliglustat tartrate in plasma) trough plasma concentrations. If Genz-99067 trough plasma concentration was \<5 ng/mL the next higher dose was administered whereas if the Genz-99067 trough plasma concentration was \>=5 ng/mL the same dose was continued. The PK assessment at Week 54 and Week 58 were used for dose adjustment after Week 56 and Week 60, respectively.
Interventions
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Eliglustat tartrate
Primary analysis period (PAP): Eliglustat tartrate capsule 50 milligram (mg) twice daily (BID) orally from Day 1 to Week 4 followed by eliglustat tartrate 50 mg or 100 mg capsule BID up to Week 8, and then eliglustat tartrate 50 mg or 100 mg or 150 mg capsule BID up to Week 52. Dose adjustments after Week 4 and Week 8 were based on Genz-99067 (active moiety of eliglustat tartrate in plasma) trough plasma concentrations. If Genz-99067 trough plasma concentration was less than (\<) 5 nanogram per milliliter \[ng/mL\] next higher dose was administered whereas if Genz-99067 trough plasma concentration was greater than or equal to (\>=) 5 ng/mL same dose was continued. Pharmacokinetic (PK) assessment at Week 2 and 6 were used for dose adjustment after Week 4 and Week 8, respectively.
Long-term treatment period (LTTP): Participants originally randomized to eliglustat in PAP continued to receive eliglustat dose, based on their Genz 99067 plasma trough concentration at Week 6.
Imiglucerase
PAP: Imiglucerase intravenous infusion every other week (q2w) up to Week 52 in doses equivalent to participant's past ERT dose prior to any unanticipated treatment interruption, dose reduction, or regimen change.
LTTP: Participants originally randomized to imiglucerase received eliglustat tartrate capsule 50 mg BID orally from Week 52+1 Day to Week 56 followed by eliglustat tartrate 50 mg or 100 mg capsule BID up to Week 60, and then eliglustat tartrate 50 mg or 100 mg or 150 mg capsule BID up to 5 years. The dose adjustments after Week 56 and Week 60 were based on Genz-99067 (active moiety of eliglustat tartrate in plasma) trough plasma concentrations. If Genz-99067 trough plasma concentration was \<5 ng/mL the next higher dose was administered whereas if the Genz-99067 trough plasma concentration was \>=5 ng/mL the same dose was continued. The PK assessment at Week 54 and Week 58 were used for dose adjustment after Week 56 and Week 60, respectively.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
Exclusion Criteria
* 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
18 Years
ALL
No
Sponsors
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Genzyme, a Sanofi Company
INDUSTRY
Responsible Party
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Principal Investigators
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Medical Monitor
Role: STUDY_DIRECTOR
Genzyme, a Sanofi Company
Locations
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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
Yale University School of Medicine
New Haven, Connecticut, United States
Northwest Oncology Hematology Associates PA
Coral Springs, Florida, 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
Albany Medical Center
Albany, New York, United States
North Shore University Medical Center
Manhasset, New York, United States
Mount Sinai School of Medicine
New York, New York, United States
New York University School of Medicine
New York, New York, United States
Duke University Medical Center
Durham, North Carolina, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States
O and O Alpan LLC
Springfield, Virginia, United States
Hospital General de Agudos J.M Ramos Mejia
Buenos Aires, , Argentina
Hospital General de Ninos Dr. Ricardo Gutierrez
Buenos Aires, , Argentina
Royal Perth Hospital
Perth, WA, , Australia
Hospital de Clinicas da Universidade Federal do Parana
Curitiba, , Brazil
Instituto de Estadual de Hematologia Arthur de Siqueria Cavalcanti
Rio de Janeiro, , 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
Charité Universitätsmedizin Berlin
Berlin, , Germany
Asklepios Klinik St. Georg
Hamburg, , Germany
Katholische Kliniken Oberhausen gem. GmbH
Oberhausen, , Germany
Azienda Ospedaliero Universitaria Careggi
Florence, , Italy
Azienda Ospedialiero-Universitaria S. Maria Della Misericordia
Udine, , Italy
Hematology Research Center of Ministry of Healthcare of the Russian Federation
Moscow, , Russia
Hospital University Miguel Servet
Zaragoza, , Spain
Cambridge University Hosptials, Addenbrookes Hospital
Cambridge, , United Kingdom
Countries
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References
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Lukina E, Watman N, Arreguin EA, Banikazemi M, Dragosky M, Iastrebner M, Rosenbaum H, Phillips M, Pastores GM, Rosenthal DI, Kaper M, Singh T, Puga AC, Bonate PL, Peterschmitt MJ. A phase 2 study of eliglustat tartrate (Genz-112638), an oral substrate reduction therapy for Gaucher disease type 1. Blood. 2010 Aug 12;116(6):893-9. doi: 10.1182/blood-2010-03-273151. Epub 2010 May 3.
Lukina E, Watman N, Arreguin EA, Dragosky M, Iastrebner M, Rosenbaum H, Phillips M, Pastores GM, Kamath RS, Rosenthal DI, Kaper M, Singh T, Puga AC, Peterschmitt MJ. Improvement in hematological, visceral, and skeletal manifestations of Gaucher disease type 1 with oral eliglustat tartrate (Genz-112638) treatment: 2-year results of a phase 2 study. Blood. 2010 Nov 18;116(20):4095-8. doi: 10.1182/blood-2010-06-293902. Epub 2010 Aug 16.
McEachern KA, Fung J, Komarnitsky S, Siegel CS, Chuang WL, Hutto E, Shayman JA, Grabowski GA, Aerts JM, Cheng SH, Copeland DP, Marshall J. A specific and potent inhibitor of glucosylceramide synthase for substrate inhibition therapy of Gaucher disease. Mol Genet Metab. 2007 Jul;91(3):259-67. doi: 10.1016/j.ymgme.2007.04.001. Epub 2007 May 16.
Kamath RS, Lukina E, Watman N, Dragosky M, Pastores GM, Arreguin EA, Rosenbaum H, Zimran A, Aguzzi R, Puga AC, Norfleet AM, Peterschmitt MJ, Rosenthal DI. Skeletal improvement in patients with Gaucher disease type 1: a phase 2 trial of oral eliglustat. Skeletal Radiol. 2014 Oct;43(10):1353-60. doi: 10.1007/s00256-014-1891-9. Epub 2014 May 10.
Lukina E, Watman N, Dragosky M, Pastores GM, Arreguin EA, Rosenbaum H, Zimran A, Angell J, Ross L, Puga AC, Peterschmitt JM. Eliglustat, an investigational oral therapy for Gaucher disease type 1: Phase 2 trial results after 4 years of treatment. Blood Cells Mol Dis. 2014 Dec;53(4):274-6. doi: 10.1016/j.bcmd.2014.04.002. Epub 2014 May 15.
Cox TM, Drelichman G, Cravo R, Balwani M, Burrow TA, Martins AM, Lukina E, Rosenbloom B, Goker-Alpan O, Watman N, El-Beshlawy A, Kishnani PS, Pedroso ML, Gaemers SJM, Tayag R, Peterschmitt MJ. Eliglustat maintains long-term clinical stability in patients with Gaucher disease type 1 stabilized on enzyme therapy. Blood. 2017 Apr 27;129(17):2375-2383. doi: 10.1182/blood-2016-12-758409. Epub 2017 Feb 6.
Cox TM, Drelichman G, Cravo R, Balwani M, Burrow TA, Martins AM, Lukina E, Rosenbloom B, Ross L, Angell J, Puga AC. Eliglustat compared with imiglucerase in patients with Gaucher's disease type 1 stabilised on enzyme replacement therapy: a phase 3, randomised, open-label, non-inferiority trial. Lancet. 2015 Jun 13;385(9985):2355-62. doi: 10.1016/S0140-6736(14)61841-9. Epub 2015 Mar 26.
Other Identifiers
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2008-005223-28
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
EFC12812
Identifier Type: OTHER
Identifier Source: secondary_id
GZGD02607
Identifier Type: -
Identifier Source: org_study_id