A Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease (ENGAGE)

Phase 3

Completed

Conditions: Gaucher Disease, Type 1

Interventions: Drug: Eliglustat tartrate
Drug: Placebo

Registration Number: NCT00891202

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.

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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 40

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active	Eliglustat tartrate	Eliglustat
Placebo	Placebo	Placebo

Primary Outcome Measures

Name	Time	Method
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	PAP Baseline (Day 1), Week 39	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

Name	Time	Method
PAP: Absolute Change From Baseline in Hemoglobin Level at Week 39	PAP Baseline (Day 1), Week 39	Absolute change = hemoglobin level at Week 39 minus hemoglobin level at baseline.
PAP: Percent Change From Baseline in Platelet Counts at Week 39	PAP Baseline (Day 1), 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.
PAP: Hemoglobin Level	PAP Baseline (Day 1)
LTTP: Absolute Change From Baseline in Hemoglobin Level at Week 234	PAP Baseline for Eliglustat (Originally on Eliglustat) arm, LTTP Baseline for Eliglustat (Originally on Placebo) arm, 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.
PAP: Percent Change From Baseline in Liver Volume (in MN) at Week 39	PAP Baseline (Day 1), 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.
LTTP: Percent Change From Baseline in Spleen Volume (in MN) at Week 234	PAP Baseline for Eliglustat (Originally on Eliglustat) arm, LTTP Baseline for Eliglustat (Originally on Placebo) arm, 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: Percent Change From Baseline in Liver Volume (in MN) at Week 234	PAP Baseline for Eliglustat (Originally on Eliglustat) arm, LTTP Baseline for Eliglustat (Originally on Placebo) arm, 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	PAP Baseline for Eliglustat (Originally on Eliglustat) arm, LTTP Baseline for Eliglustat (Originally on Placebo) arm, 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.

Trial Locations

Locations (18): Mount Sinai School of Medicine
🇺🇸
New York, New York, United States
University hospital "Alexandrovska" Sofia
🇧🇬
Sofia, Bulgaria
New York University School of Medicine, Neurology Department
🇺🇸
New York, New York, United States
Sir Mortimer B. Davis - Jewish General Hospital
🇨🇦
Montreal, Quebec, Canada
Mount Sinai Hospital and the Samuel Lunenfeld Research Institute
🇨🇦
Toronto Ontario, Canada
Hospital de San Jose
🇨🇴
Bogota, Colombia
Christian Medical College Hospital
🇮🇳
Vellore, India
Hematology Research Center of Ministry of Healthcare of the Russian Federation
🇷🇺
Moscow, Russian Federation
Rabin Medical Center, Beilinson Hospital
🇮🇱
Petach Tikvah, Israel
OCA Hospital
🇲🇽
Monterrey, Nuevo Leon, Mexico
Institut za endokrinologiju
🇷🇸
Belgrade, Serbia
Royal Free Hospital
🇬🇧
London, United Kingdom
Hopital La-Rabta
🇹🇳
Tunis, TN, Tunisia
UCSF MS Center
🇺🇸
San Francisco, California, United States
Emory University Medical Genetics
🇺🇸
Decatur, Georgia, United States
University of Kansas Medical Center, Division of Hematology/Oncology, Dept. of Medicine
🇺🇸
Westwood, Kansas, United States
Hôtel-Dieu de France University Hospital
🇱🇧
Beirut, Lebanon
Yale University School of Medicine
🇺🇸
New Haven, Connecticut, United States