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

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ClinicalTrials.gov Identifier: NCT00891202
Recruitment Status : Completed
First Posted : May 1, 2009
Results First Posted : September 3, 2014
Last Update Posted : March 3, 2017
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

Tracking Information
First Submitted Date  ICMJE April 30, 2009
First Posted Date  ICMJE May 1, 2009
Results First Submitted Date  ICMJE August 22, 2014
Results First Posted Date  ICMJE September 3, 2014
Last Update Posted Date March 3, 2017
Study Start Date  ICMJE November 2009
Actual Primary Completion Date July 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 17, 2017)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 30, 2009)
The Primary objective is to compare the effects of Genz-112638 as compared to placebo in patients with Type 1 Gaucher Disease [ Time Frame: 39 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 17, 2017)
  • PAP: Hemoglobin Level [ Time Frame: 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: 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: 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 30, 2009)
The secondary objectives for this study include an evaluation of safety and the effects on disease manifestations and disease specific bio-markers [ Time Frame: 39 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease (ENGAGE)
Official Title  ICMJE 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)
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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Gaucher Disease, Type 1
Intervention  ICMJE
  • Drug: Eliglustat tartrate
    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 Name: Genz-112638
  • Drug: 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.
Study Arms  ICMJE
  • Experimental: Active
    Eliglustat
    Intervention: Drug: Eliglustat tartrate
  • Placebo Comparator: Placebo
    Placebo
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 26, 2012)
40
Original Estimated Enrollment  ICMJE
 (submitted: April 30, 2009)
36
Actual Study Completion Date  ICMJE January 2016
Actual Primary Completion Date July 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Bulgaria,   Canada,   Colombia,   India,   Israel,   Lebanon,   Mexico,   Russian Federation,   Serbia,   Tunisia,   United Kingdom,   United States
Removed Location Countries Chile,   Georgia,   Jordan,   Netherlands,   Saudi Arabia
 
Administrative Information
NCT Number  ICMJE NCT00891202
Other Study ID Numbers  ICMJE GZGD02507
2008-005222-37 ( EudraCT Number )
EFC12813 ( Other Identifier: Sanofi )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sanofi ( Genzyme, a Sanofi Company )
Study Sponsor  ICMJE Genzyme, a Sanofi Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Monitor Genzyme, a Sanofi Company
PRS Account Sanofi
Verification Date January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP