Back to resultsA Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease (ENGAGE)
Primary Purpose
Gaucher Disease, Type 1
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Eliglustat tartrate
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Gaucher Disease, Type 1 focused on measuring Gaucher,, beta-glucosidase,, acid ß-glucosidase,, glucocerebrosidase,, glucosylceramide,, D-glucosyl-N-acylsphingosine glucohydrolase,, substrate reduction therapy
Eligibility Criteria
Inclusion Criteria:
- 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 16 years old at the time of randomization;
- The participant had a confirmed diagnosis of Gaucher disease Type 1;
- Female participants of childbearing potential must 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 has had a partial or total splenectomy;
- The participant had received pharmacological chaperones or miglustat within 6 months prior to randomization;
- The participant had received enzyme replacement therapy within 9 months prior to randomization;
- The participant had Type 2 or 3 Gaucher disease or was suspected of having Type 3 Gaucher disease;
- The participant had any clinically significant disease, other than Gaucher disease, including cardiovascular, renal, hepatic, gastrointestinal (GI), pulmonary, neurologic, endocrine, metabolic, (for example, hypokalemia, hypomagnesemia), or psychiatric disease, other medical conditions, or serious intercurrent illness that might confound the study results, or, on the opinion of the investigator, might 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.
Sites / Locations
- UCSF MS Center
- Yale University School of Medicine
- Emory University Medical Genetics
- University of Kansas Medical Center, Division of Hematology/Oncology, Dept. of Medicine
- New York University School of Medicine, Neurology Department
- Mount Sinai School of Medicine
- University hospital "Alexandrovska" Sofia
- Sir Mortimer B. Davis - Jewish General Hospital
- Mount Sinai Hospital and the Samuel Lunenfeld Research Institute
- Hospital de San Jose
- Christian Medical College Hospital
- Rabin Medical Center, Beilinson Hospital
- Hôtel-Dieu de France University Hospital
- OCA Hospital
- Hematology Research Center of Ministry of Healthcare of the Russian Federation
- Institut za endokrinologiju
- Hopital La-Rabta
- Royal Free Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Active
Placebo
Arm Description
Eliglustat
Placebo
Outcomes
Primary Outcome Measures
PAP: Percent Change From Baseline in Spleen Volume (in Multiples of Normal [MN]) at Week 39 of the Primary Analysis Period With Eliglustat Tartrate Treatment as Compared to Placebo
Percent change in spleen volume = ([spleen volume at Week 39 minus spleen volume at baseline] divided by [spleen volume at baseline]) multiplied by 100, where all volumes are in MN.
Secondary Outcome Measures
PAP: Hemoglobin Level
PAP: Absolute Change From Baseline in Hemoglobin Level at Week 39
Absolute change = hemoglobin level at Week 39 minus hemoglobin level at baseline.
PAP: Percent Change From Baseline in Liver Volume (in MN) at Week 39
Percent change in liver volume = ([liver volume at Week 39 minus liver volume at baseline] divided by [liver volume at baseline]) multiplied by 100, where all volumes are in MN.
PAP: Percent Change From Baseline in Platelet Counts at Week 39
Percent change in platelet count = ([platelet count at Week 39 minus platelet count at baseline] divided by [platelet count at baseline]) multiplied by 100.
LTTP: Percent Change From Baseline in Spleen Volume (in MN) at Week 234
Percent change in spleen volume = ([spleen volume at Week 234 minus spleen volume at baseline] divided by [spleen volume at baseline]) multiplied by 100, where all volumes are in MN. Baseline values for the original placebo participants refer to Day 1 of LTTP and baseline values for the original eliglustat participants refer to the Day 1 of PAP.
LTTP: Absolute Change From Baseline in Hemoglobin Level at Week 234
Baseline values for the original placebo participants refer to Day 1 of LTTP and baseline values for the original eliglustat participants refer to the Day 1 of PAP.
LTTP: Percent Change From Baseline in Liver Volume (in MN) at Week 234
Percent change in liver volume = ([liver volume at Week 234 minus liver volume at baseline] divided by [liver volume at baseline]) multiplied by 100, where all volumes are in MN. Baseline values for the original placebo participants refer to Day 1 of LTTP and baseline values for the original eliglustat participants refer to the Day 1 of PAP.
LTTP: Percent Change From Baseline in Platelet Counts at Week 234
Percent change in platelet count = ([platelet count at Week 234 minus platelet count at baseline] divided by [platelet count at baseline]) multiplied by 100. Baseline values for the original placebo participants refer to Day 1 of LTTP and baseline values for the original eliglustat participants refer to the Day 1 of PAP.
Full Information
NCT ID
NCT00891202
First Posted
April 30, 2009
Last Updated
January 17, 2017
Sponsor
Genzyme, a Sanofi Company
1. Study Identification
Unique Protocol Identification Number
NCT00891202
Brief Title
A Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease (ENGAGE)
Official Title
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study Confirming the Efficacy and Safety of Genz-112638 in Patients With Gaucher Disease Type 1 (ENGAGE)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
November 2009 (undefined)
Primary Completion Date
July 2012 (Actual)
Study Completion Date
January 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genzyme, a Sanofi Company
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
Detailed Description
Gaucher disease is characterized by lysosomal accumulation of glucosylceramide due to impaired glucosylceramide hydrolysis. Type 1 Gaucher disease, the most common form accounts for greater than (>) 90% of cases and does not involve the central nervous system (CNS). Typical manifestations of Type 1 Gaucher disease include splenomegaly, hepatomegaly, thrombocytopenia, anemia, skeletal pathology and decreased quality of life. The disease manifestations are caused by the accumulations of glucosylceramide (storage material) in Gaucher cells which have infiltrated the spleen and liver as well as other tissue. Eliglustat tartrate is a small molecule 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 pharmacokinetics (PK) of eliglustat tartrate in adult participants (>16 years) with Gaucher disease Type 1. The study consisted of 2 periods: The Double-Blind Primary Analysis Period (PAP [Day 1 to Week 39]) and the Long Term Treatment Period (LTTP/Open-Label Period (post-Week 39 [Day 1 of the Open-Label Period] through study completion).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gaucher Disease, Type 1
Keywords
Gaucher,, beta-glucosidase,, acid ß-glucosidase,, glucocerebrosidase,, glucosylceramide,, D-glucosyl-N-acylsphingosine glucohydrolase,, substrate reduction therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Active
Arm Type
Experimental
Arm Description
Eliglustat
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
Eliglustat tartrate
Other Intervention Name(s)
Genz-112638
Intervention Description
PAP: Eliglustat tartrate (ET) capsule 50 mg orally on Day 1 followed by ET 50 mg capsule twice daily (BID) from Day 2 to Week 4, then either ET 50 mg capsule BID (participants with Genz-99067 [active moiety of ET in plasma] trough plasma concentration >=5 ng/mL) or ET 100 mg capsule BID (participants with Genz-99067 trough plasma concentration <5 ng/mL), up to Week 39. PK assessment at Week 2 used for dose adjustment after Week 4. LTTP: Participants of the eliglustat arm in PAP who completed PAP were included in LTTP and received ET capsule 50 mg BID orally from Day 1 (post Week 39) until Week 43 followed by ET 50 mg or 100 mg capsule BID up to Week 47, then ET 50 mg or 100 mg or 150 mg capsule BID up to Week 312. Dose adjustments at Week 43 and Week 47 were based on Genz-99067 trough plasma concentrations (if trough plasma concentration <5 ng/mL: next higher dose administered; if >=5 ng/mL: same dose continued) at Week 41 & Week 45, respectively.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
PAP: Matching placebo capsule once daily on Day 1 followed by matching placebo capsule BID from Day 2 through Week 39. LTTP: Participants of the placebo arm in PAP who completed PAP were included in LTTP and received eliglustat tartrate from Day 1 (post Week 39) up to Week 312. Day 1 (post Week 39) was considered as baseline for LTTP. On Day 1, participants received eliglustat tartrate capsule 50 mg BID orally until Week 43 followed by eliglustat tartrate 50 mg or 100 mg capsule BID up to Week 47, then eliglustat tartrate 50 mg or 100 mg or 150 mg capsule BID up to Week 312. Dose adjustments at Week 43 and Week 47 were based on Genz-99067 trough plasma concentrations (if trough plasma concentration <5 ng/mL: next higher dose administered; if >=5 ng/mL: same dose continued) at Week 41 & Week 45, respectively.
Primary Outcome Measure Information:
Title
PAP: Percent Change From Baseline in Spleen Volume (in Multiples of Normal [MN]) at Week 39 of the Primary Analysis Period With Eliglustat Tartrate Treatment as Compared to Placebo
Description
Percent change in spleen volume = ([spleen volume at Week 39 minus spleen volume at baseline] divided by [spleen volume at baseline]) multiplied by 100, where all volumes are in MN.
Time Frame
PAP Baseline (Day 1), Week 39
Secondary Outcome Measure Information:
Title
PAP: Hemoglobin Level
Time Frame
PAP Baseline (Day 1)
Title
PAP: Absolute Change From Baseline in Hemoglobin Level at Week 39
Description
Absolute change = hemoglobin level at Week 39 minus hemoglobin level at baseline.
Time Frame
PAP Baseline (Day 1), Week 39
Title
PAP: Percent Change From Baseline in Liver Volume (in MN) at Week 39
Description
Percent change in liver volume = ([liver volume at Week 39 minus liver volume at baseline] divided by [liver volume at baseline]) multiplied by 100, where all volumes are in MN.
Time Frame
PAP Baseline (Day 1), Week 39
Title
PAP: Percent Change From Baseline in Platelet Counts at Week 39
Description
Percent change in platelet count = ([platelet count at Week 39 minus platelet count at baseline] divided by [platelet count at baseline]) multiplied by 100.
Time Frame
PAP Baseline (Day 1), Week 39
Title
LTTP: Percent Change From Baseline in Spleen Volume (in MN) at Week 234
Description
Percent change in spleen volume = ([spleen volume at Week 234 minus spleen volume at baseline] divided by [spleen volume at baseline]) multiplied by 100, where all volumes are in MN. Baseline values for the original placebo participants refer to Day 1 of LTTP and baseline values for the original eliglustat participants refer to the Day 1 of PAP.
Time Frame
PAP Baseline for Eliglustat (Originally on Eliglustat) arm, LTTP Baseline for Eliglustat (Originally on Placebo) arm, Week 234
Title
LTTP: Absolute Change From Baseline in Hemoglobin Level at Week 234
Description
Baseline values for the original placebo participants refer to Day 1 of LTTP and baseline values for the original eliglustat participants refer to the Day 1 of PAP.
Time Frame
PAP Baseline for Eliglustat (Originally on Eliglustat) arm, LTTP Baseline for Eliglustat (Originally on Placebo) arm, Week 234
Title
LTTP: Percent Change From Baseline in Liver Volume (in MN) at Week 234
Description
Percent change in liver volume = ([liver volume at Week 234 minus liver volume at baseline] divided by [liver volume at baseline]) multiplied by 100, where all volumes are in MN. Baseline values for the original placebo participants refer to Day 1 of LTTP and baseline values for the original eliglustat participants refer to the Day 1 of PAP.
Time Frame
PAP Baseline for Eliglustat (Originally on Eliglustat) arm, LTTP Baseline for Eliglustat (Originally on Placebo) arm, Week 234
Title
LTTP: Percent Change From Baseline in Platelet Counts at Week 234
Description
Percent change in platelet count = ([platelet count at Week 234 minus platelet count at baseline] divided by [platelet count at baseline]) multiplied by 100. Baseline values for the original placebo participants refer to Day 1 of LTTP and baseline values for the original eliglustat participants refer to the Day 1 of PAP.
Time Frame
PAP Baseline for Eliglustat (Originally on Eliglustat) arm, LTTP Baseline for Eliglustat (Originally on Placebo) arm, Week 234
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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 16 years old at the time of randomization;
The participant had a confirmed diagnosis of Gaucher disease Type 1;
Female participants of childbearing potential must 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 has had a partial or total splenectomy;
The participant had received pharmacological chaperones or miglustat within 6 months prior to randomization;
The participant had received enzyme replacement therapy within 9 months prior to randomization;
The participant had Type 2 or 3 Gaucher disease or was suspected of having Type 3 Gaucher disease;
The participant had any clinically significant disease, other than Gaucher disease, including cardiovascular, renal, hepatic, gastrointestinal (GI), pulmonary, neurologic, endocrine, metabolic, (for example, hypokalemia, hypomagnesemia), or psychiatric disease, other medical conditions, or serious intercurrent illness that might confound the study results, or, on the opinion of the investigator, might 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Genzyme, a Sanofi Company
Official's Role
Study Director
Facility Information:
Facility Name
UCSF MS Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Yale University School of Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
Emory University Medical Genetics
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States
Facility Name
University of Kansas Medical Center, Division of Hematology/Oncology, Dept. of Medicine
City
Westwood
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
New York University School of Medicine, Neurology Department
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Mount Sinai School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
University hospital "Alexandrovska" Sofia
City
Sofia
ZIP/Postal Code
1431
Country
Bulgaria
Facility Name
Sir Mortimer B. Davis - Jewish General Hospital
City
Montreal, Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Facility Name
Mount Sinai Hospital and the Samuel Lunenfeld Research Institute
City
Toronto Ontario
ZIP/Postal Code
M5G 1X5
Country
Canada
Facility Name
Hospital de San Jose
City
Bogota
Country
Colombia
Facility Name
Christian Medical College Hospital
City
Vellore
ZIP/Postal Code
632004
Country
India
Facility Name
Rabin Medical Center, Beilinson Hospital
City
Petach Tikvah
ZIP/Postal Code
49100
Country
Israel
Facility Name
Hôtel-Dieu de France University Hospital
City
Beirut
Country
Lebanon
Facility Name
OCA Hospital
City
Monterrey, Nuevo Leon
Country
Mexico
Facility Name
Hematology Research Center of Ministry of Healthcare of the Russian Federation
City
Moscow
ZIP/Postal Code
125167
Country
Russian Federation
Facility Name
Institut za endokrinologiju
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Hopital La-Rabta
City
Tunis
State/Province
TN
ZIP/Postal Code
1007
Country
Tunisia
Facility Name
Royal Free Hospital
City
London
ZIP/Postal Code
NW3 2QG
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
20439622
Citation
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.
Results Reference
background
PubMed Identifier
20713962
Citation
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. Erratum In: Blood. 2011 May 19;117(20):5551.
Results Reference
background
PubMed Identifier
17509920
Citation
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.
Results Reference
background
PubMed Identifier
20864621
Citation
Peterschmitt MJ, Burke A, Blankstein L, Smith SE, Puga AC, Kramer WG, Harris JA, Mathews D, Bonate PL. Safety, tolerability, and pharmacokinetics of eliglustat tartrate (Genz-112638) after single doses, multiple doses, and food in healthy volunteers. J Clin Pharmacol. 2011 May;51(5):695-705. doi: 10.1177/0091270010372387. Epub 2010 Sep 23.
Results Reference
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PubMed Identifier
24816856
Citation
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.
Results Reference
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PubMed Identifier
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Citation
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.
Results Reference
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PubMed Identifier
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Citation
Mistry PK, Lukina E, Ben Turkia H, Amato D, Baris H, Dasouki M, Ghosn M, Mehta A, Packman S, Pastores G, Petakov M, Assouline S, Balwani M, Danda S, Hadjiev E, Ortega A, Shankar S, Solano MH, Ross L, Angell J, Peterschmitt MJ. Effect of oral eliglustat on splenomegaly in patients with Gaucher disease type 1: the ENGAGE randomized clinical trial. JAMA. 2015 Feb 17;313(7):695-706. doi: 10.1001/jama.2015.459.
Results Reference
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PubMed Identifier
34161616
Citation
Mistry PK, Lukina E, Ben Turkia H, Shankar SP, Baris Feldman H, Ghosn M, Mehta A, Packman S, Lau H, Petakov M, Assouline S, Balwani M, Danda S, Hadjiev E, Ortega A, Foster MC, Gaemers SJM, Peterschmitt MJ. Clinical outcomes after 4.5 years of eliglustat therapy for Gaucher disease type 1: Phase 3 ENGAGE trial final results. Am J Hematol. 2021 Sep 1;96(9):1156-1165. doi: 10.1002/ajh.26276. Epub 2021 Jul 11.
Results Reference
derived
Learn more about this trial
A Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease (ENGAGE)
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