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

January 17, 2017 updated by: Genzyme, a Sanofi Company

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)

This Phase 3 study was designed to confirm the efficacy and safety of eliglustat tartrate (Genz-112638) in participants with Gaucher disease Type 1.

Study Overview

Status

Completed

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).

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Sofia, Bulgaria, 1431
        • University hospital "Alexandrovska" Sofia
      • Montreal, Quebec, Canada, H3T 1E2
        • Sir Mortimer B. Davis - Jewish General Hospital
      • Toronto Ontario, Canada, M5G 1X5
        • Mount Sinai Hospital and the Samuel Lunenfeld Research Institute
      • Bogota, Colombia
        • Hospital De San Jose
      • Vellore, India, 632004
        • Christian Medical College Hospital
      • Petach Tikvah, Israel, 49100
        • Rabin Medical Center, Beilinson Hospital
      • Beirut, Lebanon
        • Hôtel-Dieu De France University Hospital
      • Monterrey, Nuevo Leon, Mexico
        • OCA Hospital
      • Moscow, Russian Federation, 125167
        • Hematology Research Center of Ministry of Healthcare of the Russian Federation
      • Belgrade, Serbia, 11000
        • Institut za endokrinologiju
    • TN
      • Tunis, TN, Tunisia, 1007
        • Hopital La-Rabta
      • London, United Kingdom, NW3 2QG
        • Royal Free Hospital
    • California
      • San Francisco, California, United States, 94143
        • UCSF MS Center
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale University School Of Medicine
    • Georgia
      • Decatur, Georgia, United States, 30033
        • Emory University Medical Genetics
    • Kansas
      • Westwood, Kansas, United States, 66160
        • University of Kansas Medical Center, Division of Hematology/Oncology, Dept. of Medicine
    • New York
      • New York, New York, United States, 10029
        • Mount Sinai School of Medicine
      • New York, New York, United States, 10016
        • New York University School of Medicine, Neurology Department

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
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.
Experimental: Active
Eliglustat
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.
Other Names:
  • Genz-112638

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: 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.
PAP Baseline (Day 1), Week 39

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2009

Primary Completion (Actual)

July 1, 2012

Study Completion (Actual)

January 1, 2016

Study Registration Dates

First Submitted

April 30, 2009

First Submitted That Met QC Criteria

April 30, 2009

First Posted (Estimate)

May 1, 2009

Study Record Updates

Last Update Posted (Actual)

March 3, 2017

Last Update Submitted That Met QC Criteria

January 17, 2017

Last Verified

January 1, 2017

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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