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Trial record 42 of 103 for:    Gaucher Disease

A Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease Who Have Reached Therapeutic Goals With Enzyme Replacement Therapy (ENCORE) (ENCORE)

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ClinicalTrials.gov Identifier: NCT00943111
Recruitment Status : Completed
First Posted : July 22, 2009
Results First Posted : September 4, 2014
Last Update Posted : November 25, 2016
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: Gaucher Disease, Type 1
Interventions: Drug: Eliglustat tartrate
Drug: Imiglucerase

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A total of 209 participants were screened, of which 46 participants were screen failure and 3 participants withdrew prior to randomization. A total of 160 participants were enrolled in this study.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
All enrolled participants received eliglustat or imiglucerase in 52 week primary analysis period (PAP). After 52-weeks PAP, all participants who remained on-study, received eliglustat in the long-term treatment period (LTTP) for up to 5 years.

Reporting Groups
  Description
Eliglustat: PAP Eliglustat tartrate (Genz-112638) capsule 50 milligram (mg) twice daily (BID) orally from Day 1 to Week 4 followed by eliglustat tartrate 50 mg or 100 mg capsule BID up to Week 8, and then eliglustat tartrate 50 mg or 100 mg or 150 mg capsule BID up to Week 52. The dose adjustments after Week 4 and Week 8 were based on Genz-99067 (active moiety of eliglustat tartrate in plasma) trough plasma concentrations. If Genz-99067 trough plasma concentration was less than [<] 5 nanogram per milliliter [ng/mL] the next higher dose was administered whereas if the Genz-99067 trough plasma concentration was greater than or equal to [>=] 5 ng/mL the same dose was continued. The pharmacokinetic (PK) assessment at Week 2 and Week 6 were used for dose adjustment after Week 4 and Week 8, respectively.
Imiglucerase: PAP Imiglucerase (Cerezyme®) intravenous infusion every other week (q2w) up to Week 52 in doses equivalent to participant’s past enzyme replacement therapy (ERT) dose prior to any unanticipated treatment interruption, dose reduction, or regimen change.
Eliglustat: LTTP

Participants from both the arms of PAP who completed PAP were included in this arm of LTTP.

Participants originally randomized to eliglustat in PAP continued to receive eliglustat dose, based on their Genz 99067 plasma trough concentration at Week 6.

Participants originally randomized to imiglucerase received eliglustat tartrate capsule 50 mg BID orally from Week 52+1 Day to Week 56 followed by eliglustat tartrate 50 mg or 100 mg capsule BID up to Week 60, and then eliglustat tartrate 50 mg or 100 mg or 150 mg capsule BID up to 5 years. The dose adjustments after Week 56 and Week 60 were based on Genz-99067 (active moiety of eliglustat tartrate in plasma) trough plasma concentrations. If Genz-99067 trough plasma concentration was <5 ng/mL next higher dose was administered whereas if the Genz-99067 trough plasma concentration was >=5 ng/mL the same dose was continued. PK assessment at Week 54 and Week 58 were used for dose adjustment after Week 56 and Week 60, respectively.


Participant Flow for 2 periods

Period 1:   52-Weeks Primary Analysis Period
    Eliglustat: PAP   Imiglucerase: PAP   Eliglustat: LTTP
STARTED   106   54   0 
Treated   106   53   0 
COMPLETED   104   52   0 
NOT COMPLETED   2   2   0 
Adverse Event                2                1                0 
Non-Compliance with Study Drug                0                1                0 

Period 2:   5 Years Long-term Treatment Period
    Eliglustat: PAP   Imiglucerase: PAP   Eliglustat: LTTP
STARTED   0   0   152 [1] 
COMPLETED   0   0   77 
NOT COMPLETED   0   0   75 
Transition to commercial eliglustat                0                0                51 
Adverse Event                0                0                9 
Withdrawal by Subject                0                0                8 
Pregnancy                0                0                4 
Lost to Follow-up                0                0                1 
Other than specified above                0                0                2 
[1] Participants from both the arms of PAP who completed PAP and remained on-study



  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.
Full analysis set (FAS) for PAP: included all participants who signed informed consent and received at least 1 dose of study drug (Imiglucerase or eliglustat).

Reporting Groups
  Description
Eliglustat: PAP Eliglustat tartrate 50 mg capsule BID orally from Day 1 to Week 4, followed by eliglustat tartrate 50, 100 or 150 mg capsule BID orally up to Week 52.
Imiglucerase: PAP Imiglucerase intravenous infusion q2w up to Week 52 in doses equivalent to participant’s past ERT dose prior to any unanticipated treatment interruption, dose reduction, or regimen change.
Total Total of all reporting groups

Baseline Measures
   Eliglustat: PAP   Imiglucerase: PAP   Total 
Overall Participants Analyzed 
[Units: Participants]
 106   53   159 
Age 
[Units: Years]
Mean (Standard Deviation)
 37.6  (14.17)   37.5  (14.92)   37.5  (14.37) 
Gender 
[Units: Participants]
     
Female   59   28   87 
Male   47   25   72 
Race/Ethnicity, Customized 
[Units: Participants]
     
Race: White   98   48   146 
Race: Black or African American   6   4   10 
Race: Asian   1   1   2 
Race: White/American Indian   1   0   1 
Ethnicity: Hispanic or Latino   42   19   61 
Ethnicity: Not Hispanic or Latino   64   34   98 
Body Mass Index (BMI) [1] 
[Units: Kilogram per square meter (kg/m^2)]
Mean (Standard Deviation)
 25.2  (5.24)   24.5  (4.51)   24.9  (5.01) 
[1] BMI was calculated as ([weight in kg] divided by [height in cm multiplied by 0.01]^2).
Weight 
[Units: Kilogram (kg)]
Mean (Standard Deviation)
 70.8  (16.82)   67.8  (14.44)   69.8  (16.08) 
Height 
[Units: Centimeter (cm)]
Mean (Standard Deviation)
 167.6  (9.92)   166.2  (9.56)   167.1  (9.79) 


  Outcome Measures

1.  Primary:   Percentage of Participants Who Remained Stable for 52 Weeks During the Primary Analysis Period   [ Time Frame: Baseline up to Week 52 ]

2.  Primary:   Percentage of Participants Who Remained Stable Annually for 4 Years During the LTTP   [ Time Frame: Week 52 up to week 208 ]

3.  Secondary:   Total T-Scores for Bone Mineral Density   [ Time Frame: Baseline ]

4.  Secondary:   Absolute Change From Baseline in Total T-Scores for Bone Mineral Density at Week 52   [ Time Frame: Baseline, Week 52 ]

5.  Secondary:   Total Z-Scores for Bone Mineral Density   [ Time Frame: Baseline ]

6.  Secondary:   Absolute Change From Baseline in Total Z-Scores for Bone Mineral Density at Week 52   [ Time Frame: Baseline, Week 52 ]

7.  Secondary:   Hemoglobin Level   [ Time Frame: Baseline ]

8.  Secondary:   Absolute Change From Baseline in Hemoglobin Levels at Week 52   [ Time Frame: Baseline, Week 52 ]

9.  Secondary:   Percent Change From Baseline in Platelet Counts at Week 52   [ Time Frame: Baseline, Week 52 ]

10.  Secondary:   Percent Change From Baseline in Spleen Volume (MN) at Week 52   [ Time Frame: Baseline, Week 52 ]

11.  Secondary:   Percent Change From Baseline in Liver Volume (in MN) at Week 52   [ Time Frame: Baseline, Week 52 ]

12.  Secondary:   Absolute Change From Baseline in Total T-Scores for Bone Mineral Density at Week 208   [ Time Frame: Baseline, Week 208 ]

13.  Secondary:   Absolute Change From Baseline in Total Z-Scores for Bone Mineral Density at Week 208   [ Time Frame: Baseline, Week 208 ]

14.  Secondary:   Absolute Change From Baseline in Hemoglobin Levels at Week 208   [ Time Frame: Baseline, Week 208 ]

15.  Secondary:   Percent Change From Baseline in Platelet Counts at Week 208   [ Time Frame: Baseline, Week 208 ]

16.  Secondary:   Percent Change From Baseline in Spleen Volume (in MN) at Week 208   [ Time Frame: Baseline, Week 208 ]

17.  Secondary:   Percent Change From Baseline in Liver Volume (in MN) at Week 208   [ Time Frame: Baseline, Week 208 ]


  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: Contact-us@sanofi.com


Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT00943111     History of Changes
Other Study ID Numbers: GZGD02607
2008-005223-28 ( EudraCT Number )
EFC12812 ( Other Identifier: Sanofi )
First Submitted: July 20, 2009
First Posted: July 22, 2009
Results First Submitted: August 22, 2014
Results First Posted: September 4, 2014
Last Update Posted: November 25, 2016