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A Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease to Evaluate Once Daily Versus Twice Daily Dosing (EDGE)

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ClinicalTrials.gov Identifier: NCT01074944
Recruitment Status : Completed
First Posted : February 24, 2010
Results First Posted : December 2, 2016
Last Update Posted : February 6, 2017
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Gaucher Disease
Intervention: Drug: Eliglustat tartrate

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted at 45 centers in 17 countries between 1 June 2010 and 6 October 2015. A total of 219 participants were screened, out of which 170 entered into the lead in period (LIP). Remaining 48 participants were screen failures and 1 participant withdrew before entering into the LIP.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participant flow divided into 4 periods: LIP:to assess randomization criteria. Primary analysis period (PAP):to assess therapeutic efficacy at 2 dosing regimen in randomized participants. Long-term treatment period (LTTP): to assess long term efficacy. Extended treatment period (ETP):those who were non-randomized after LIP continued in this period.

Reporting Groups
  Description
LIP, Eliglustat All participants (except in Japan) received eliglustat 50 mg, twice daily (BID) on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual pharmacokinetics (PK) data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks.
PAP, Eliglustat: Once Daily All participants who were randomized after meeting all randomization criteria (defined as: no more than 1 bone crisis and was free of other clinically symptomatic bone disease [such as bone pain attributable to osteonecrosis and/or pathological fractures) during the first 6 months of the LIP; mean hemoglobin level of ≥11 g/dL [if female] and ≥12 g/dL [if male]; mean platelet count ≥100,000/mm^3; spleen volume ≤10 times of normal; liver volume ≤1.5 times of normal; had a dose of 50 mg BID or 100 mg BID of eliglustat for at least 4 months and a peak (2-hour) Genz-99067 plasma concentration of <50 ng/mL) after either 26, 52 or 78 weeks of LIP received eliglustat capsules at the total daily dose (TDD) of 100 mg or 200 mg (the TDD they were on before randomization) once daily (QD) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
PAP, Eliglustat: Twice Daily All participants who were randomized after meeting all randomization criteria (defined as: no more than 1 bone crisis and was free of other clinically symptomatic bone disease [such as bone pain attributable to osteonecrosis and/or pathological fractures) during the first 6 months of the LIP; mean hemoglobin level of ≥11 g/dL [if female] and ≥12 g/dL [if male]; mean platelet count ≥100,000/mm^3; spleen volume ≤10 times of normal; liver volume ≤1.5 times of normal; had a dose of 50 mg BID or 100 mg BID of eliglustat for at least 4 months and a peak (2-hour) Genz-99067 plasma concentration of <50 ng/mL) after either 26, 52 or 78 weeks of LIP, received eliglustat at the TDD 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
LTTP, Eliglustat All participants who entered PAP continued their blinded randomized treatment for first 4 weeks. Participants who at Week 52 of PAP maintained their therapeutic goals (defined as: no more than 2 bone crisis during PAP [with no more than 1 bone crisis during either first 6 months or later 6 months of PAP] and is free of other clinically symptomatic bone disease during PAP; hemoglobin level not decreased by >1.5 g/dL from Baseline for PAP [defined as last available assessment prior to randomization]; platelet count not decreased by >25% from Baseline for PAP; spleen volume not increased by 25% from Baseline for PAP; liver volume not increased by >20% from Baseline for PAP), continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) QD till the end of the study. The participants who did not maintain all their therapeutic goals continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) BID till the end of the study.
ETP, Eliglustat All participants who did not meet all the randomization criteria at Week 78 of the LIP continued in the ETP and received eliglustat capsules at the same dose as they were receiving at the end of LIP till the end of the study.

Participant Flow for 4 periods

Period 1:   Lead-in Period (up to 78 Weeks)
    LIP, Eliglustat   PAP, Eliglustat: Once Daily   PAP, Eliglustat: Twice Daily   LTTP, Eliglustat   ETP, Eliglustat
STARTED   170 [1]   0   0   0   0 
COMPLETED   157   0   0   0   0 
NOT COMPLETED   13   0   0   0   0 
Adverse Event                2                0                0                0                0 
Non-Compliance With Protocol                1                0                0                0                0 
Pregnancy                4                0                0                0                0 
Withdrawal by Subject                6                0                0                0                0 
[1] LIP conducted to assess randomization criteria of all participants in single reporting arm.

Period 2:   Primary Analysis Period (up to 52 Weeks)
    LIP, Eliglustat   PAP, Eliglustat: Once Daily   PAP, Eliglustat: Twice Daily   LTTP, Eliglustat   ETP, Eliglustat
STARTED   0   65 [1]   66 [1]   0   0 
COMPLETED   0   54   60   0   0 
NOT COMPLETED   0   11   6   0   0 
Adverse Event                0                2                3                0                0 
Treatment Failure                0                6                1                0                0 
Withdrawal by Subject                0                1                1                0                0 
Pregnancy                0                1                0                0                0 
Non-Compliant to Protocol                0                1                1                0                0 
[1] Participants who were randomized after LIP received treatment in PAP.

Period 3:   Long Term Treatment
    LIP, Eliglustat   PAP, Eliglustat: Once Daily   PAP, Eliglustat: Twice Daily   LTTP, Eliglustat   ETP, Eliglustat
STARTED   0   0   0   121 [1]   0 
COMPLETED   0   0   0   95   0 
NOT COMPLETED   0   0   0   26   0 
Adverse Event                0                0                0                3                0 
Lost to Follow-up                0                0                0                2                0 
Transitioned to Commercial Eliglustat                0                0                0                18                0 
Entered in Period, But Not Treated                0                0                0                1                0 
Withdrawal by Subject                0                0                0                2                0 
[1] Participants who completed PAP (114) including those who considered as treatment failure in PAP (7).

Period 4:   Extended Treatment (up to 42 Months)
    LIP, Eliglustat   PAP, Eliglustat: Once Daily   PAP, Eliglustat: Twice Daily   LTTP, Eliglustat   ETP, Eliglustat
STARTED   0   0   0   0   25 [1] 
COMPLETED   0   0   0   0   20 
NOT COMPLETED   0   0   0   0   5 
Pregnancy                0                0                0                0                2 
Transitioned to Commercial Eliglustat                0                0                0                0                3 
[1] Participants who were failed to meet the randomization criteria during the lead-in period.



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All treated (AT) analysis set included all participants who received at least 1 dose of eliglustat during LIP.

Reporting Groups
  Description
All Participants All participants who received treatment in LIP (eliglustat 50 mg BID on Day 1 titrated up to 100 mg BID [50 or 100 mg capsules] based on their individual PK data for up to 78 weeks [except for the participants in Japan]. Participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID [50 or 100 mg capsules] based on their individual PK data for up to 78 weeks) and assessed for randomization.

Baseline Measures
   All Participants 
Overall Participants Analyzed 
[Units: Participants]
 170 
Age 
[Units: Years]
Mean (Standard Deviation)
 37.7  (15.1) 
Gender 
[Units: Participants]
Count of Participants
 
Female      81  47.6% 
Male      89  52.4% 


  Outcome Measures

1.  Primary:   PAP: Percentage of Participants Who Remained Stable for 52 Weeks During the PAP   [ Time Frame: PAP Baseline up to the end of PAP (Week 52) ]

2.  Secondary:   PAP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26 and 52   [ Time Frame: Baseline, Week 26, Week 52 ]

3.  Secondary:   PAP: Mean Platelet Count at Baseline, Weeks 26, 52   [ Time Frame: Baseline, Week 26, Week 52 ]

4.  Secondary:   PAP: Mean Spleen Volume at Baseline, Weeks 26, 52   [ Time Frame: Baseline, Week 26, Week 52 ]

5.  Secondary:   PAP: Mean Liver Volume at Baseline, Weeks 26, 52   [ Time Frame: Baseline, Week 26 and Week 52 ]

6.  Secondary:   PAP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26 and Week 52   [ Time Frame: Baseline, Week 26, Week 52 ]

7.  Secondary:   PAP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26 and Week 52   [ Time Frame: Baseline, Week 26 and week 52 ]

8.  Secondary:   PAP: Mean Biomarker Macrophage Inflammatory Protein-1 Beta (MIP1-beta) Value at Baseline, Weeks 26, 52   [ Time Frame: Baseline, Week 26, Week 52 ]

9.  Secondary:   PAP: Bone Mineral Density (BMD) at Baseline and Week 52   [ Time Frame: Baseline, Week 52 ]

10.  Secondary:   PAP: Total T-Scores for BMD at Baseline and Week 52   [ Time Frame: Baseline, Week 52 ]

11.  Secondary:   PAP: Total Z-scores for BMD at Baseline and Week 52   [ Time Frame: Baseline, Week 52 ]

12.  Secondary:   PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52.   [ Time Frame: Baseline, Week 26 and Week 52 ]

13.  Secondary:   PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52   [ Time Frame: Baseline, Week 26, and Week 52 ]

14.  Secondary:   PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52   [ Time Frame: Baseline, Week 26, and Week 52 ]

15.  Secondary:   PAP: Total Bone Marrow Burden Score (BMB) at Baseline and Week 52   [ Time Frame: Baseline, Week 52 ]

16.  Secondary:   LIP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26, 52 and 78   [ Time Frame: Baseline, Week 26, Week, 52, and Week 78 ]

17.  Secondary:   LIP: Mean Platelet Count at Baseline, Weeks 26, 52 and 78   [ Time Frame: Baseline, Week 26, Week 52, Week 78 ]

18.  Secondary:   LIP: Mean Liver Volume at Baseline, Weeks 26, 52 and 78   [ Time Frame: Baseline, Week 26, Week 52, Week 78 ]

19.  Secondary:   LIP: Mean Spleen Volume at Baseline, Weeks 26, 52 and 78   [ Time Frame: Baseline, Week 26, Week 52, Week 78 ]

20.  Secondary:   LIP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26, 52, and 78   [ Time Frame: Baseline, Week 26, Week 52 and Week 78 ]

21.  Secondary:   LIP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26, Week 52, and Week 78   [ Time Frame: Baseline, Week 26, Week 52 and Week 78 ]

22.  Secondary:   LIP: Mean Biomarker (MIP1-beta) Value at Baseline, Week 78   [ Time Frame: Baseline and Week 78 ]

23.  Secondary:   LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78   [ Time Frame: Baseline, Week 26, Week 52, Week 78 ]

24.  Secondary:   LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78   [ Time Frame: Baseline, Week 26, Week 52, Week 78 ]

25.  Secondary:   LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78   [ Time Frame: Baseline, Week 26, Week 52, Week 78 ]

26.  Secondary:   LTTP: Percentage of Participants Who Maintained a Stable Bone Criterion ,Hemoglobin Level, Platelet Count, Liver Volume and Spleen Volume at 1 Year and 2 Years   [ Time Frame: 1 Year, 2 Years ]

27.  Secondary:   LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years   [ Time Frame: Baseline, 1 year, and 2 years ]

28.  Secondary:   LTTP: Number of Participants With Bone Crises Assessment at Baseline, 1 Year and 2 Years   [ Time Frame: Baseline, 1 year and 2 years ]

29.  Secondary:   LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years   [ Time Frame: Baseline, 1 year and 2 years ]

30.  Secondary:   LTTP: Bone Mineral Density (BMD) at Baseline, 1 Year, and 2 Years   [ Time Frame: Baseline, 1 year, and 2 years ]

31.  Secondary:   LTTP: Total T-Scores for BMD at Baseline, 1 Year, and 2 Years   [ Time Frame: Baseline, 1 year, and 2 years ]

32.  Secondary:   LTTP: Total Z-scores for BMD at Baseline, 1 Year, and 2 Years   [ Time Frame: Baseline, 1 year, and 2 years ]

33.  Secondary:   LTTP: Total Bone Marrow Burden Score (BMB) at Baseline, 1 Year, and 2 Years   [ Time Frame: Baseline, 1 year, and 2 years ]

34.  Secondary:   LTTP: Mean Biomarker (Chitotriosidase) Value at Baseline, 1 Year, and 2 Years   [ Time Frame: Baseline, 1 year, and 2 years ]

35.  Secondary:   LTTP: Mean Biomarker (GL-1 on DBS) Value at Baseline, 1 Year, and 2 Years   [ Time Frame: Baseline, 1 year, and 2 years ]

36.  Secondary:   LTTP: Mean Biomarker (MIP1-beta) Value at Baseline, 1 Year, and 2 Years   [ Time Frame: Baseline, 1 year, and 2 years ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Trial Transparency Team
Organization: Sanofi
e-mail: Contact­US@sanofi.com


Publications:

Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT01074944     History of Changes
Other Study ID Numbers: GZGD03109
2009-015811-42 ( EudraCT Number )
EFC12818 ( Other Identifier: Sanofi )
First Submitted: February 23, 2010
First Posted: February 24, 2010
Results First Submitted: October 7, 2016
Results First Posted: December 2, 2016
Last Update Posted: February 6, 2017