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A Medical Research Study Designed to Determine if Venglustat Can be a Future Treatment for ADPKD Patients (STAGED-PKD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03523728
Recruitment Status : Terminated (Interim analysis for futility of the Stage 1 of the EFC15392 study met the protocol specified stopping rule based on the primary endpoint. EFC15392 study was stopped for futility based on prespecified criteria and recommendation from DMC)
First Posted : May 14, 2018
Results First Posted : November 9, 2022
Last Update Posted : November 9, 2022
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Polycystic Kidney, Autosomal Dominant
Interventions Drug: Venglustat
Drug: Placebo
Enrollment 478
Recruitment Details This study was conducted at 93 sites that enrolled participants in 23 countries. A total of 478 participants were enrolled from 04 October 2018 to 01 June 2021. Study was conducted in 2 stages: Stage 1 and Stage 2.
Pre-assignment Details Participants who completed 24 months of treatment in either Stage 1 or Stage 2 of EFC15392 had option to enroll in an open-label long-term extension study LTS15823 (NCT ID: NCT04705051).
Arm/Group Title Stage 1- Placebo Stage 1- Venglustat 8 mg Stage 1- Venglustat 15 mg Stage 2- Placebo Stage 2- Venglustat 15 mg
Hide Arm/Group Description Participants from Stage 1 were randomized to receive 2 capsules of placebo matched to venglustat once daily for treatment period of 24 months. Participants from Stage 1 were randomized to receive venglustat 8 milligrams (mg) (i.e., 2 capsules of 4 mg) once daily for treatment period of 24 months. Participants from Stage 1 were randomized to receive 1 capsule of venglustat 15 mg and 1 capsule of placebo matched to venglustat once daily for treatment period of 24 months. Participants from Stage 2 were randomized to receive 1 capsule of placebo matched to venglustat once daily for treatment period of 24 months. Participants from Stage 2 were randomized to receive 1 capsule of venglustat 15 mg once daily for treatment period of 24 months.
Period Title: Stage 1 (24 Months)
Started 78 78 80 0 0
Completed 12 10 12 0 0
Not Completed 66 68 68 0 0
Reason Not Completed
Adverse Event             2             2             4             0             0
Progressive disease             0             0             1             0             0
Lack of Efficacy             2             0             0             0             0
Poor compliance to protocol             1             0             0             0             0
Withdrawal by Subject             6             5             7             0             0
Study terminated by sponsor             54             59             56             0             0
Other-Unspecified             1             2             0             0             0
Period Title: Stage 2 (24 Months)
Started 0 0 0 123 [1] 119 [1]
Treated 0 0 0 122 119
Estimated Glomerular Filtration Rate (eGFR) Between 45 and 89.9 mL/Min/1.73 m^2 at Screening 0 0 0 97 90
eGFR Between 30 and 44.9 mL/Min/1.73 m^2 at Screening 0 0 0 25 29
Completed 0 0 0 0 0
Not Completed 0 0 0 123 119
Reason Not Completed
Adverse Event             0             0             0             1             2
Withdrawal by Subject             0             0             0             0             4
Study terminated by sponsor             0             0             0             119             110
Other-Unspecified             0             0             0             2             3
Randomized and not treated             0             0             0             1             0
[1]
Stage 1 and Stage 2 were separate population.
Arm/Group Title Stage 1- Placebo Stage 1- Venglustat 8 mg Stage 1- Venglustat 15 mg Stage 2- Placebo Stage 2- Venglustat 15 mg Total Title
Hide Arm/Group Description Participants from Stage 1 were randomized to receive 2 capsules of placebo matched to venglustat once daily for treatment period of 24 months. Participants from Stage 1 were randomized to receive venglustat 8 mg (i.e., 2 capsules of 4 mg) once daily for treatment period of 24 months. Participants from Stage 1 were randomized to receive 1 capsule of venglustat 15 mg and 1 capsule of placebo matched to venglustat once daily for treatment period of 24 months. Participants from Stage 2 were randomized to receive 1 capsule of placebo matched to venglustat once daily for treatment period of 24 months. Participants from Stage 2 were randomized to receive 1 capsule of venglustat 15 mg once daily for treatment period of 24 months. [Not Specified]
Overall Number of Baseline Participants 78 78 80 123 119 478
Hide Baseline Analysis Population Description
Analysis was performed on all participants randomized in the study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 78 participants 78 participants 80 participants 123 participants 119 participants 478 participants
42.6  (6.0) 41.7  (6.9) 43.6  (5.7) 41.7  (6.9) 42.1  (6.7) 42.2  (6.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 78 participants 78 participants 80 participants 123 participants 119 participants 478 participants
Female
37
  47.4%
31
  39.7%
34
  42.5%
46
  37.4%
48
  40.3%
196
  41.0%
Male
41
  52.6%
47
  60.3%
46
  57.5%
77
  62.6%
71
  59.7%
282
  59.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 78 participants 78 participants 80 participants 123 participants 119 participants 478 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.8%
0
   0.0%
1
   0.2%
Asian
27
  34.6%
27
  34.6%
27
  33.8%
52
  42.3%
55
  46.2%
188
  39.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
1
   1.3%
0
   0.0%
0
   0.0%
1
   0.2%
Black or African American
0
   0.0%
1
   1.3%
0
   0.0%
2
   1.6%
0
   0.0%
3
   0.6%
White
48
  61.5%
50
  64.1%
52
  65.0%
66
  53.7%
64
  53.8%
280
  58.6%
More than one race
1
   1.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.2%
Unknown or Not Reported
2
   2.6%
0
   0.0%
0
   0.0%
2
   1.6%
0
   0.0%
4
   0.8%
1.Primary Outcome
Title Annualized Slope of Change in Total Kidney Volume (TKV) From Baseline to Month 18: Stage 1
Hide Description Total kidney volume is a measure for assessing disease progression in participants with ADPKD, a prognostic biomarker of renal function decline and progression to end-stage renal disease. Kidney volume was assessed using magnetic resonance imaging (MRI). The annualized slope of change in TKV (in percentage [%] per year) in each treatment group was obtained from the back-transformation of the mean slope of log10-transformed TKV obtained from the linear mixed effect model. The model included fix effects of treatment (venglustat 15 mg, venglustat 8 mg or placebo), mayo imaging classification (as per randomization stratification factor: class 1C versus 1D versus 1E), time (as continuous variable in years), treatment * time interaction and mayo imaging classification * time interaction and included random intercept and slope.
Time Frame From Baseline to Month 18
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Stage 1 intent-to-treat (ITT) population that includes all participants randomized in Stage 1 and were analyzed according to the intervention allocated by randomization (venglustat 15 mg, venglustat 8 mg or placebo). Here, 'Overall number of participants analyzed' signifies participants who were evaluable for the outcome measure.
Arm/Group Title Stage 1- Placebo Stage 1- Venglustat 8 mg Stage 1- Venglustat 15 mg
Hide Arm/Group Description:
Participants from Stage 1 were randomized to receive 2 capsules of placebo matched to venglustat once daily for treatment period of 24 months.
Participants from Stage 1 were randomized to receive venglustat 8 mg (i.e., 2 capsules of 4 mg) once daily for treatment period of 24 months.
Participants from Stage 1 were randomized to receive 1 capsule of venglustat 15 mg and 1 capsule of placebo matched to venglustat once daily for treatment period of 24 months.
Overall Number of Participants Analyzed 78 78 79
Geometric Least Squares Mean (95% Confidence Interval)
Unit of Measure: percent change in TKV/year
6.35
(5.10 to 7.62)
7.71
(6.46 to 8.98)
6.38
(5.11 to 7.66)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Stage 1- Placebo, Stage 1- Venglustat 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.1367
Comments [Not Specified]
Method linear mixed effect model
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative difference
Estimated Value 21.32
Confidence Interval (2-Sided) 95%
-5.77 to 58.22
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Stage 1- Placebo, Stage 1- Venglustat 15 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.9812
Comments [Not Specified]
Method linear mixed effect model
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative difference
Estimated Value 0.34
Confidence Interval (2-Sided) 95%
-24.57 to 33.36
Estimation Comments [Not Specified]
2.Primary Outcome
Title Annualized Rate of Change in Estimated Glomerular Filtration Rate (eGFR) (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) From Baseline to Month 24: Combined Stage 1 and Stage 2
Hide Description An eGFR was used to measure level of kidney function and determine the stage of kidney disease in ADPKD participants. Baseline eGFR was defined for each participant as the average of eGFR values assessed prior or equal to first dose of study drug or randomization for participants randomized and not exposed. Annualized rate of change in eGFR in each treatment group was obtained from the linear mixed effect model including the fixed categorical effects of treatment group (venglustat 15 mg, venglustat 8 mg or placebo), mayo imaging classification (as per interactive response technology [IRT]: 1C, 1D, 1E), time (as continuous variable in years), treatment-by-time, mayo imaging classification-by-time, and included random intercept and slope.
Time Frame From Baseline to Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Combined Stage 1 and Stage 2 ITT population that included all participants with an eGFR between 45 and 89.9 mL/min/1.73 m^2 at screening who are randomized in Stage 1 or Stage 2 and were analyzed according to the intervention allocated by randomization (venglustat 15 mg, venglustat 8 mg or placebo). Data for this outcome measure (OM) was planned to be collected and analyzed for combined Stage 1 and Stage 2 population as pre-specified in protocol.
Arm/Group Title Placebo Venglustat 8 mg Venglustat 15 mg
Hide Arm/Group Description:
All participants from Stage 1 or Stage 2 were randomized to receive placebo matched to venglustat once daily for treatment period of 24 months.
Participants from Stage 1 were randomized to receive venglustat 8 mg (i.e., 2 capsules of 4 mg) once daily for treatment period of 24 months.
All participants from Stage 1 or Stage 2 were randomized to receive 1 capsule of venglustat 15 mg once daily for treatment period of 24 months.
Overall Number of Participants Analyzed 175 78 170
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mL/min/1.73 m^2/year
-2.40
(-3.30 to -1.49)
-4.82
(-5.82 to -3.83)
-4.89
(-5.80 to -3.99)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Venglustat 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0005
Comments [Not Specified]
Method linear mixed effect model
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative difference
Estimated Value 101.32
Confidence Interval (2-Sided) 95%
35.63 to 233.72
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Venglustat 15 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0002
Comments [Not Specified]
Method linear mixed effect model
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative difference
Estimated Value 104.17
Confidence Interval (2-Sided) 95%
39.54 to 236.45
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Annualized Rate of Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Month 24: Stage 1
Hide Description An eGFR was used to measure level of kidney function and determine the stage of kidney disease in ADPKD participants. Baseline eGFR was defined for each participant as the average of eGFR values assessed prior or equal to first dose of study drug or randomization for participants randomized and not exposed. Annualized rate of change in eGFR was obtained from the linear mixed effect model including the fixed categorical effects of treatment group, mayo imaging classification (as per IRT), time (as continuous variable in years), treatment-by-time, mayo imaging classification-by-time, and included random intercept and slope. Due to early termination of study for futility, the two-steps analysis initially planned was not applicable, then the annualized rate of change from baseline in eGFR in Stage 1 population were assessed using all data available up to database lock (i.e., including Month 24 assessment). As this is a slope, it allowed to have more data and to reduce variability.
Time Frame From Baseline to Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Stage 1 ITT population.
Arm/Group Title Stage 1- Placebo Stage 1- Venglustat 8 mg Stage 1- Venglustat 15 mg
Hide Arm/Group Description:
Participants from Stage 1 were randomized to receive 2 capsules of placebo matched to venglustat once daily for treatment period of 24 months.
Participants from Stage 1 were randomized to receive venglustat 8 mg (i.e., 2 capsules of 4 mg) once daily for treatment period of 24 months.
Participants from Stage 1 were randomized to receive 1 capsule of venglustat 15 mg and 1 capsule of placebo matched to venglustat once daily for treatment period of 24 months.
Overall Number of Participants Analyzed 78 78 80
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mL/min/1.73 m^2/year
-3.14
(-4.09 to -2.18)
-4.74
(-5.68 to -3.80)
-4.59
(-5.53 to -3.65)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Stage 1- Placebo, Stage 1- Venglustat 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0197
Comments [Not Specified]
Method linear mixed effect model
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative difference
Estimated Value 51.01
Confidence Interval (2-Sided) 95%
7.01 to 125.45
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Stage 1- Placebo, Stage 1- Venglustat 15 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0337
Comments [Not Specified]
Method linear mixed effect model
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative difference
Estimated Value 46.36
Confidence Interval (2-Sided) 95%
3.21 to 119.01
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Annualized Slope of Change in Total Kidney Volume (TKV) From Baseline to Month 18: Combined Stage 1 and Stage 2
Hide Description Total kidney volume is a measure for assessing disease progression in participants with ADPKD, a prognostic biomarker of renal function decline and progression to end-stage renal disease. Kidney volume was assessed using MRI. The annualized slope of change in TKV (in % per year) in each treatment group was obtained from the back-transformation of the mean slope of log10-transformed TKV obtained from the linear mixed effect model. The model included fix effects of treatment (venglustat 15 mg, venglustat 8 mg or placebo), mayo imaging classification (as per randomization stratification factor: class 1C versus 1D versus 1E), time (as continuous variable in years), treatment * time interaction and mayo imaging classification * time interaction and included random intercept and slope.
Time Frame From Baseline to Month 18
Hide Outcome Measure Data
Hide Analysis Population Description
As no post-baseline MRI data were collected in Stage 2 due to early study discontinuation, the analysis of TKV in Combined Stage 1 and Stage 2 was not done.
Arm/Group Title Placebo Venglustat 8 mg Venglustat 15 mg
Hide Arm/Group Description:
All participants from Stage 1 or Stage 2 were randomized to receive placebo matched to venglustat once daily for treatment period of 24 months.
Participants from Stage 1 were randomized to receive venglustat 8 mg (i.e., 2 capsules of 4 mg) once daily for treatment period of 24 months.
All participants from Stage 1 or Stage 2 were randomized to receive 1 capsule of venglustat 15 mg once daily for treatment period of 24 months.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Change in Pain Severity as Measured by Brief Pain Inventory-Short Form (BPI-SF)-Item 3 Scale Score From Baseline to Month 18: Stage 1
Hide Description The BPI-SF is a validated, self-administered questionnaire designed to measure a participant's perceived level of pain. The BPI-SF consisted of 15 items that use a numeric rating scale (NRS) to assess pain severity and pain interference in the past 24 hours and the past week. BPI-SF Item 3 asks participants to "Please rate your pain by marking the box beside the number that best describes your pain at its worst in the past 24 hours." The NRS ranged from 0 (no pain) to 10 (worst imaginable pain), where higher scores indicates greater intensity of pain. Least-squares (LS) means, and standard errors (SE) were estimated from mixed-effect model with repeated measures (MMRM) analysis.
Time Frame From Baseline to Month 18
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Stage 1 ITT population. Here, 'Overall number of participants analyzed' signifies participants who were evaluable for the outcome measure.
Arm/Group Title Stage 1- Placebo Stage 1- Venglustat 8 mg Stage 1- Venglustat 15 mg
Hide Arm/Group Description:
Participants from Stage 1 were randomized to receive 2 capsules of placebo matched to venglustat once daily for treatment period of 24 months.
Participants from Stage 1 were randomized to receive venglustat 8 mg (i.e., 2 capsules of 4 mg) once daily for treatment period of 24 months.
Participants from Stage 1 were randomized to receive 1 capsule of venglustat 15 mg and 1 capsule of placebo matched to venglustat once daily for treatment period of 24 months.
Overall Number of Participants Analyzed 69 65 65
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-0.09  (0.15) 0.01  (0.17) -0.35  (0.16)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Stage 1- Placebo, Stage 1- Venglustat 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.6374
Comments [Not Specified]
Method Mixed effect model with repeated measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean difference
Estimated Value 0.11
Confidence Interval (2-Sided) 95%
-0.342 to 0.556
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.23
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Stage 1- Placebo, Stage 1- Venglustat 15 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.2560
Comments [Not Specified]
Method Mixed effect model with repeated measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean difference
Estimated Value -0.25
Confidence Interval (2-Sided) 95%
-0.689 to 0.185
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.22
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change in Pain Severity as Measured by Brief Pain Inventory-Short Form (BPI-SF)-Item 3 Scale Score From Baseline to Month 24: Combined Stage 1 and Stage 2
Hide Description The BPI-SF is a validated, self-administered questionnaire designed to measure a participant's perceived level of pain. The BPI-SF consisted of 15 items that use a NRS to assess pain severity and pain interference in the past 24 hours and the past week. BPI-SF Item 3 asks participants to "Please rate your pain by marking the box beside the number that best describes your pain at its worst in the past 24 hours." The NRS ranged from 0 (no pain) to 10 (worst imaginable pain), where higher scores indicate greater intensity of pain. LS means and SE were estimated from MMRM analysis.
Time Frame From Baseline to Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Combined Stage 1 and Stage 2 ITT population. Here, 'Overall number of participants analyzed' signifies participants who were evaluable for the outcome measure. Data for this OM was planned to be collected and analyzed for combined Stage 1 and Stage 2 population as pre-specified in protocol.
Arm/Group Title Placebo Venglustat 8 mg Venglustat 15 mg
Hide Arm/Group Description:
All participants from Stage 1 or Stage 2 were randomized to receive placebo matched to venglustat once daily for treatment period of 24 months.
Participants from Stage 1 were randomized to receive venglustat 8 mg (i.e., 2 capsules of 4 mg) once daily for treatment period of 24 months.
All participants from Stage 1 or Stage 2 were randomized to receive 1 capsule of venglustat 15 mg once daily for treatment period of 24 months.
Overall Number of Participants Analyzed 133 65 126
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-0.20  (0.23) -0.31  (0.36) -0.36  (0.23)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Venglustat 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.7900
Comments [Not Specified]
Method Mixed effect model with repeated measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean difference
Estimated Value -0.11
Confidence Interval (2-Sided) 95%
-0.971 to 0.747
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.42
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Venglustat 15 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.6322
Comments [Not Specified]
Method Mixed effect model with repeated measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean difference
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-0.808 to 0.500
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.32
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change in Fatigue Severity as Measured by Brief Fatigue Inventory (BFI-SF)-Item 3 Scale Score From Baseline to Month 18: Stage 1
Hide Description The BFI-SF is a 10-item, validated, self-administered questionnaire that was originally developed to assess fatigue severity. The 10-items were measured on a 0-10 scale, with 0 being 'does not interfere' and 10 being 'completely interferes.' BFI - Item 3 asks participants to 'Please rate your fatigue (weariness, tiredness) by circling the one number that best describes your worst level of fatigue during the past 24 hours. The NRS ranged from 0 (no fatigue) to 10 (worst imaginable fatigue). Higher global scores were associated with more severe fatigue. LS means and SE were estimated from MMRM analysis.
Time Frame From Baseline to Month 18
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Stage 1 ITT population. Here, 'Overall number of participants analyzed' signifies participants who were evaluable for the outcome measure.
Arm/Group Title Stage 1- Placebo Stage 1- Venglustat 8 mg Stage I- Venglustat 15 mg
Hide Arm/Group Description:
Participants from Stage 1 were randomized to receive 2 capsules of placebo matched to venglustat once daily for treatment period of 24 months.
Participants from Stage 1 were randomized to receive venglustat 8 mg (i.e., 2 capsules of 4 mg) once daily for treatment period of 24 months.
Participants from Stage 1 were randomized to receive 1 capsule of venglustat 15 mg and 1 capsule of placebo matched to venglustat once daily for treatment period of 24 months.
Overall Number of Participants Analyzed 69 65 65
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-0.26  (0.23) -0.10  (0.25) -0.64  (0.24)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Stage 1- Placebo, Stage 1- Venglustat 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.6245
Comments [Not Specified]
Method Mixed effect model with repeated measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean difference
Estimated Value 0.17
Confidence Interval (2-Sided) 95%
-0.506 to 0.839
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.34
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Stage 1- Placebo, Stage I- Venglustat 15 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.2567
Comments [Not Specified]
Method Mixed effect model with repeated measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean difference
Estimated Value -0.38
Confidence Interval (2-Sided) 95%
-1.044 to 0.281
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.33
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change in Fatigue Severity as Measured by Brief Fatigue Inventory (BFI-SF)-Item 3 Scale Score From Baseline to Month 24: Combined Stage 1 and Stage 2
Hide Description The BFI-SF is a 10-item, validated, self-administered questionnaire that was originally developed to assess fatigue severity. The 10-items were measured on a 0-10 scale, with 0 being 'does not interfere' and 10 being 'completely interferes.' BFI - Item 3 asks participants to "Please rate your fatigue (weariness, tiredness) by circling the one number that best describes your worst level of fatigue during the past 24 hours. The NRS ranged from 0 (no fatigue) to 10 (worst imaginable fatigue). Higher global scores were associated with more severe fatigue. LS means and SE were estimated from MMRM analysis.
Time Frame From Baseline to Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Combined Stage 1 and Stage 2 ITT population. Here, 'Overall number of participants analyzed' signifies participants who were evaluable for the outcome measure. Data for this OM was planned to be collected and analyzed for combined Stage 1 and Stage 2 population as pre-specified in protocol.
Arm/Group Title Placebo Venglustat 8 mg Venglustat 15 mg
Hide Arm/Group Description:
All participants from Stage 1 or Stage 2 were randomized to receive placebo matched to venglustat once daily for treatment period of 24 months.
Participants from Stage 1 were randomized to receive venglustat 8 mg (i.e., 2 capsules of 4 mg) once daily for treatment period of 24 months.
All participants from Stage 1 or Stage 2 were randomized to receive 1 capsule of venglustat 15 mg once daily for treatment period of 24 months.
Overall Number of Participants Analyzed 133 65 126
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
0.02  (0.38) -0.85  (0.55) -0.51  (0.38)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Venglustat 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.2023
Comments [Not Specified]
Method Mixed effect model with repeated measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean difference
Estimated Value -0.87
Confidence Interval (2-Sided) 95%
-2.232 to 0.485
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.68
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Venglustat 15 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.3205
Comments [Not Specified]
Method Mixed effect model with repeated measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean difference
Estimated Value -0.54
Confidence Interval (2-Sided) 95%
-1.610 to 0.537
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.53
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Pharmacokinetics: Plasma Concentration of Venglustat: Stage 1
Hide Description Venglustat plasma concentrations was determined using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Data for this outcome measure was not planned to be collected and analyzed for placebo arm.
Time Frame Day 1: 3 hours Post-Dose, Month 1: Pre-Dose and 3 hours Post-Dose, Month 6: Pre-Dose, Month 18: Pre-Dose
Hide Outcome Measure Data
Hide Analysis Population Description
Analysed on Stage 1 pharmacokinetic (PK) population that included all participants randomized in Stage 1 who took at least one dose of study drug and had at least one post-baseline PK assessment; analyzed according to the intervention they actually received. Here, "number analyzed" signifies participants with available data for each specified category.
Arm/Group Title Stage 1- Venglustat 8 mg Stage 1- Venglustat 15 mg
Hide Arm/Group Description:
Participants from Stage 1 were randomized to receive venglustat 8 mg (i.e., 2 capsules of 4 mg) once daily for treatment period of 24 months.
Participants from Stage 1 were randomized to receive 1 capsule of venglustat 15 mg and 1 capsule of placebo matched to venglustat once daily for treatment period of 24 months.
Overall Number of Participants Analyzed 78 80
Mean (Standard Deviation)
Unit of Measure: nanograms per milliliter
Day 1: 3 hours Post-Dose Number Analyzed 65 participants 73 participants
27.8  (11.9) 50.9  (22.5)
Month 1: Pre-Dose Number Analyzed 72 participants 63 participants
54.7  (19.2) 103.9  (50.2)
Month 1: 3 hours Post-Dose Number Analyzed 75 participants 64 participants
82.1  (24.7) 154.6  (61.1)
Months 6: Pre-Dose Number Analyzed 47 participants 54 participants
57.5  (23.5) 106.2  (56.3)
Months 18: Pre-Dose Number Analyzed 41 participants 41 participants
58.3  (22.0) 120.3  (73.1)
10.Secondary Outcome
Title Pharmacokinetics: Plasma Concentration of Venglustat: Stage 2
Hide Description Venglustat plasma concentrations was determined using a validated LC-MS/MS method. Data for this outcome measure was not planned to be collected and analyzed for placebo arm.
Time Frame Month 1: Pre-dose and 3 hours Post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Stage 2 PK population that included all participants with an eGFR between 45 and 89.9 mL/min/1.73 m^2 at screening who were randomized in Stage 2, who took at least one dose of study drug and who had at least one post-baseline PK assessment. Participants were analyzed according to study drug they actually received. Here, "number analyzed" signifies participants with available data for each specified category.
Arm/Group Title Stage 2- Venglustat 15 mg
Hide Arm/Group Description:
Participants from Stage 2 were randomized to receive 1 capsule of venglustat 15 mg once daily for treatment period of 24 months.
Overall Number of Participants Analyzed 77
Mean (Standard Deviation)
Unit of Measure: nanograms per milliliter
Month 1: Pre-Dose Number Analyzed 60 participants
109.3  (60.7)
Month 1: 3 hours Post-Dose Number Analyzed 61 participants
163.5  (79.7)
11.Secondary Outcome
Title Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs): Stage 1
Hide Description An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. A serious adverse event (SAE) was any untoward medical occurrence that at any dose: results in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was a medically important event. TEAEs were AEs that developed, worsened or became serious during the treatment-emergent (TE) period (defined as the time from the first investigational medicinal product [IMP] administration up to the last IMP administration in EFC15392 study + 30 days or up to the first visit in LTS15823 study, whichever comes earlier).
Time Frame From the first IMP administration up to the last IMP administration in EFC15392 study + 30 days (i.e., up to 25 months) or up to the first visit in LTS15823 study, whichever comes earlier
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Stage 1 safety population that included all participants randomized in Stage 1 who took at least one dose or part of a dose of the double-blind IMP, analyzed according to the treatment actually received (venglustat 15 mg, venglustat 8 mg, or placebo)
Arm/Group Title Stage 1- Placebo Stage 1- Venglustat 8 mg Stage 1- Venglustat 15 mg
Hide Arm/Group Description:
Participants from Stage 1 were randomized to receive 2 capsules of placebo matched to venglustat once daily for treatment period of 24 months.
Participants from Stage 1 were randomized to receive venglustat 8 mg (i.e., 2 capsules of 4 mg) once daily for treatment period of 24 months.
Participants from Stage 1 were randomized to receive 1 capsule of venglustat 15 mg and 1 capsule of placebo matched to venglustat once daily for treatment period of 24 months.
Overall Number of Participants Analyzed 78 78 80
Measure Type: Count of Participants
Unit of Measure: Participants
TEAEs
62
  79.5%
65
  83.3%
70
  87.5%
TESAEs
8
  10.3%
15
  19.2%
19
  23.8%
12.Secondary Outcome
Title Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs): Combined Stage 1 and Stage 2
Hide Description An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. SAE was any untoward medical occurrence that at any dose: results in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was a medically important event. TEAEs were AEs that developed, worsened or became serious during the TE period (defined as the time from the first IMP administration up to the last IMP administration in EFC15392 study + 30 days or up to the first visit in LTS15823 study, whichever comes earlier).
Time Frame From the first IMP administration up to the last IMP administration in EFC15392 study + 30 days (i.e., up to 25 months) or up to the first visit in LTS15823 study, whichever comes earlier
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on extended Combined Stage 1 and Stage 2 safety population that included all participants with an eGFR between 45 and 89.9 mL/min/1.73 m^2 at screening who were randomized in Stage 1 or Stage 2 and who took at least one dose or part of a dose of IMP, analyzed according to treatment actually received. Data for this OM was planned to be collected and analyzed for combined Stage 1 and Stage 2 population as pre-specified in protocol.
Arm/Group Title Placebo Venglustat 8 mg Venglustat 15 mg
Hide Arm/Group Description:
All participants from Stage 1 or Stage 2 were randomized to receive placebo matched to venglustat once daily for treatment period of 24 months.
Participants from Stage 1 were randomized to receive venglustat 8 mg (i.e., 2 capsules of 4 mg) once daily for treatment period of 24 months.
All participants from Stage 1 or Stage 2 were randomized to receive 1 capsule of venglustat 15 mg once daily for treatment period of 24 months.
Overall Number of Participants Analyzed 200 78 199
Measure Type: Count of Participants
Unit of Measure: Participants
TEAEs
128
  64.0%
65
  83.3%
143
  71.9%
TESAEs
14
   7.0%
15
  19.2%
26
  13.1%
13.Secondary Outcome
Title Number of Participants With Potentially Clinically Significant Abnormalities: Hematology: Combined Stage 1 and Stage 2
Hide Description Criteria for potentially clinically significant abnormalities: Hemoglobin: less than or equal to (<=) 115 grams per liter (g/L) [Male]; <=95 g/L [Female]; greater than or equal to (>=) 185 g/L [Male]; >=165 g/L [Female]; Decrease from baseline >=20 g/L; Hematocrit: <=0.37 volume/volume (v/v) [Male]; <=0.32 v/v [Female]; >=0.55 v/v [Male]; >=0.5 v/v [Female]; Erythrocyte (red blood cells [RBC]): >=6*10^12 per liter (/L); Platelet: less than (<) 100*10^9/L; >=700*10^9/L; Leukocyte (white blood cells [WBC]): <3*10^9/L [Non-Black]; <2*10^9/L [Black], >=16*10^9/L; Neutrophils: <1.5*10^9/L [Non-Black]; <1*10^9/L [Black]; Lymphocytes: greater than (>) 4*10^9/L, Monocytes: >0.7*10^9/L; Basophils: >0.1*10^9/L; and Eosinophils: >0.5*10^9/L or >upper limit of normal (ULN) (if ULN >=0.5*10^9/L).
Time Frame From the first IMP administration up to the last IMP administration in EFC15392 study + 30 days (i.e., up to 25 months) or up to the first visit in LTS15823 study, whichever comes earlier
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on extended Combined Stage 1 and Stage 2 safety population. Here, "number analyzed" signifies participants with available data for specified category. Data for this OM was planned to be collected and analyzed for combined Stage 1 and Stage 2 population as pre-specified in protocol.
Arm/Group Title Placebo Venglustat 8 mg Venglustat 15 mg
Hide Arm/Group Description:
All participants from Stage 1 or Stage 2 were randomized to receive placebo matched to venglustat once daily for treatment period of 24 months.
Participants from Stage 1 were randomized to receive venglustat 8 mg (i.e., 2 capsules of 4 mg) once daily for treatment period of 24 months.
All participants from Stage 1 or Stage 2 were randomized to receive 1 capsule of venglustat 15 mg once daily for treatment period of 24 months.
Overall Number of Participants Analyzed 200 78 199
Measure Type: Count of Participants
Unit of Measure: Participants
Hemoglobin: <=115 g/L (Male); <=95 g/L (Female) Number Analyzed 187 participants 78 participants 190 participants
7
   3.7%
3
   3.8%
5
   2.6%
Hemoglobin: >=185 g/L (Male); >=165 g/L (Female) Number Analyzed 187 participants 78 participants 190 participants
0
   0.0%
0
   0.0%
0
   0.0%
Hemoglobin: Decrease from baseline >=20 g/L Number Analyzed 186 participants 78 participants 190 participants
4
   2.2%
7
   9.0%
5
   2.6%
Hematocrit: <=0.37 v/v (Male); <=0.32 v/v (Female) Number Analyzed 186 participants 78 participants 190 participants
40
  21.5%
20
  25.6%
42
  22.1%
Hematocrit: >=0.55 v/v (Male); >=0.5 v/v (Female) Number Analyzed 186 participants 78 participants 190 participants
0
   0.0%
0
   0.0%
0
   0.0%
Erythrocyte (RBC): >=6 * 10^12/L Number Analyzed 187 participants 78 participants 190 participants
1
   0.5%
0
   0.0%
1
   0.5%
Platelet: <100*10^9/L Number Analyzed 187 participants 78 participants 190 participants
0
   0.0%
2
   2.6%
1
   0.5%
Platelet: >=700*10^9/L Number Analyzed 187 participants 78 participants 190 participants
0
   0.0%
0
   0.0%
0
   0.0%
Leukocyte (WBC): <3*10^9/L (Non-Black); <2*10^9/L (Black) Number Analyzed 187 participants 78 participants 190 participants
1
   0.5%
2
   2.6%
4
   2.1%
Leukocyte (WBC): >=16*10^9/L Number Analyzed 187 participants 78 participants 190 participants
0
   0.0%
2
   2.6%
1
   0.5%
Neutrophils: <1.5*10^9/L (Non-Black); <1*10^9/L (Black) Number Analyzed 187 participants 78 participants 190 participants
1
   0.5%
1
   1.3%
3
   1.6%
Lymphocytes: >4*10^9/L Number Analyzed 187 participants 78 participants 190 participants
0
   0.0%
1
   1.3%
0
   0.0%
Monocytes >0.7*10^9/L Number Analyzed 187 participants 78 participants 190 participants
6
   3.2%
3
   3.8%
7
   3.7%
Basophils: >0.1*10^9/L Number Analyzed 187 participants 78 participants 190 participants
33
  17.6%
5
   6.4%
8
   4.2%
Eosinophils: >0.5*10^9/L or >ULN Number Analyzed 187 participants 78 participants 190 participants
7
   3.7%
2
   2.6%
1
   0.5%
14.Secondary Outcome
Title Number of Participants With Potentially Clinically Significant Abnormalities: Clinical Chemistry: Combined Stage 1 and Stage 2
Hide Description Criteria for potentially clinically significant abnormalities: Glucose: <=3.9 millimoles per liter (mmol/L) and <lower limit of normal (LLN): >=11.1 mmol/L (unfasted); >=7 mmol/L (fasted); Albumin:<=25 g/L; Sodium: <=129 mmol/L; >=160 mmol/L; Potassium: <3 mmol/L; >=5.5 mmol/L; Chloride: <80 mmol/L, >115 mmol/L; Creatinine: >=150 micro millimoles per liter (mcmol/L) (Adults); >=30% change from Baseline; >=100% change from Baseline, Urea Nitrogen: >=17 mmol/L; Alanine Aminotransferase (ALT): >3 ULN; Aspartate Aminotransferase (AST): >3 ULN; Alkaline Phosphatase: >1.5 ULN; Total Bilirubin: >1.5 ULN, >2 ULN; ALT >3 ULN and Bilirubin >2 ULN; and Direct Bilirubin >35% Bilirubin and Bilirubin >1.5 ULN.
Time Frame From the first IMP administration up to the last IMP administration in EFC15392 study + 30 days (i.e., up to 25 months) or up to the first visit in LTS15823 study, whichever comes earlier
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on extended Combined Stage 1 and Stage 2 safety population. Here, "number analyzed" signifies participants with available data for each specified category. Data for this OM was planned to be collected and analyzed for combined Stage 1 and Stage 2 population as pre-specified in protocol.
Arm/Group Title Placebo Venglustat 8 mg Venglustat 15 mg
Hide Arm/Group Description:
All participants from Stage 1 or Stage 2 were randomized to receive placebo matched to venglustat once daily for treatment period of 24 months.
Participants from Stage 1 were randomized to receive venglustat 8 mg (i.e., 2 capsules of 4 mg) once daily for treatment period of 24 months.
All participants from Stage 1 or Stage 2 were randomized to receive 1 capsule of venglustat 15 mg once daily for treatment period of 24 months.
Overall Number of Participants Analyzed 200 78 199
Measure Type: Count of Participants
Unit of Measure: Participants
Glucose: <=3.9 mmol/L and <LLN Number Analyzed 196 participants 78 participants 196 participants
17
   8.7%
5
   6.4%
12
   6.1%
Glucose: >=11.1 mmol/L (unfasted); >=7 mmol/L (fasted) Number Analyzed 196 participants 78 participants 196 participants
10
   5.1%
5
   6.4%
19
   9.7%
Albumin: <=25 g/L Number Analyzed 196 participants 78 participants 196 participants
0
   0.0%
0
   0.0%
0
   0.0%
Sodium: <=129 mmol/L Number Analyzed 196 participants 78 participants 196 participants
1
   0.5%
0
   0.0%
3
   1.5%
Sodium: >=160 mmol/L Number Analyzed 196 participants 78 participants 196 participants
0
   0.0%
0
   0.0%
0
   0.0%
Potassium: <3 mmol/L Number Analyzed 196 participants 78 participants 196 participants
0
   0.0%
1
   1.3%
0
   0.0%
Potassium: >=5.5 mmol/L Number Analyzed 196 participants 78 participants 196 participants
5
   2.6%
5
   6.4%
11
   5.6%
Chloride: <80 mmol/L Number Analyzed 196 participants 78 participants 196 participants
0
   0.0%
1
   1.3%
0
   0.0%
Chloride: >115 mmol/L Number Analyzed 196 participants 78 participants 196 participants
1
   0.5%
0
   0.0%
0
   0.0%
Creatinine: >=150 mcmol/L (Adults) Number Analyzed 196 participants 78 participants 196 participants
50
  25.5%
21
  26.9%
70
  35.7%
Creatinine: >=30% change from Baseline Number Analyzed 196 participants 78 participants 196 participants
12
   6.1%
18
  23.1%
25
  12.8%
Creatinine: >=100% change from Baseline Number Analyzed 196 participants 78 participants 196 participants
0
   0.0%
1
   1.3%
4
   2.0%
Urea Nitrogen: >=17 mmol/L Number Analyzed 196 participants 78 participants 196 participants
1
   0.5%
0
   0.0%
6
   3.1%
ALT: > 3 ULN Number Analyzed 196 participants 78 participants 196 participants
0
   0.0%
0
   0.0%
0
   0.0%
AST: >3 ULN Number Analyzed 196 participants 78 participants 196 participants
0
   0.0%
0
   0.0%
0
   0.0%
Alkaline Phosphatase: >1.5 ULN Number Analyzed 196 participants 78 participants 196 participants
3
   1.5%
0
   0.0%
0
   0.0%
Total Bilirubin: >1.5 ULN Number Analyzed 196 participants 78 participants 196 participants
2
   1.0%
0
   0.0%
1
   0.5%
Total Bilirubin: >2 ULN Number Analyzed 196 participants 78 participants 196 participants
0
   0.0%
0
   0.0%
0
   0.0%
ALT >3 ULN and Bilirubin >2 ULN Number Analyzed 196 participants 78 participants 196 participants
0
   0.0%
0
   0.0%
0
   0.0%
Direct Bilirubin >35% Bilirubin and Bilirubin >1.5 ULN Number Analyzed 195 participants 78 participants 196 participants
2
   1.0%
0
   0.0%
0
   0.0%
15.Secondary Outcome
Title Number of Participants With Potentially and Clinically Significant Abnormalities: Urinalysis: Combined Stage 1 and Stage 2
Hide Description Criteria for potentially clinically significant abnormalities: Urine pH: <=4.6 and >=8.
Time Frame From the first IMP administration up to the last IMP administration in EFC15392 study + 30 days (i.e., up to 25 months) or up to the first visit in LTS15823 study, whichever comes earlier
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on extended Combined Stage 1 and Stage 2 safety population. Here, "number analyzed" signifies participants with available data for each specified category. Data for this OM was planned to be collected and analyzed for combined Stage 1 and Stage 2 population as pre-specified in protocol.
Arm/Group Title Placebo Venglustat 8 mg Venglustat 15 mg
Hide Arm/Group Description:
All participants from Stage 1 or Stage 2 were randomized to receive placebo matched to venglustat once daily for treatment period of 24 months.
Participants from Stage 1 were randomized to receive venglustat 8 mg (i.e., 2 capsules of 4 mg) once daily for treatment period of 24 months.
All participants from Stage 1 or Stage 2 were randomized to receive 1 capsule of venglustat 15 mg once daily for treatment period of 24 months.
Overall Number of Participants Analyzed 200 78 199
Measure Type: Count of Participants
Unit of Measure: Participants
Urine pH: <=4.6 Number Analyzed 156 participants 70 participants 153 participants
0
   0.0%
0
   0.0%
0
   0.0%
Urine pH: >=8 Number Analyzed 156 participants 70 participants 153 participants
0
   0.0%
0
   0.0%
0
   0.0%
16.Secondary Outcome
Title Number of Participants With Potentially and Clinically Significant Abnormalities: Vital Signs: Combined Stage 1 and Stage 2
Hide Description Criteria for potentially clinically significant abnormalities: Sitting Systolic Blood Pressure: <=95 millimeters of Mercury (mmHg) and decrease from Baseline >=20 mmHg; >=160 mmHg and increase from Baseline >=20 mmHg; Sitting Diastolic Blood Pressure: <=45 mmHg and decrease from Baseline >=10 mmHg, >=110 mmHg and increase from Baseline >=10 mmHg; Sitting Heart Rate: <=50 beats/minute and decrease from Baseline >=20 beats/minute; >=120 beats/minute and increase from Baseline >=20 beats/minute; and Weight: >=5% decrease from Baseline; >=5% increase from Baseline.
Time Frame From the first IMP administration up to the last IMP administration in EFC15392 study + 30 days (i.e., up to 25 months) or up to the first visit in LTS15823 study, whichever comes earlier
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on extended Combined Stage 1 and Stage 2 safety population. Here, "number analyzed" signifies participants with available data for each specified category. Data for this OM was planned to be collected and analyzed for combined Stage 1 and Stage 2 population as pre-specified in protocol.
Arm/Group Title Placebo Venglustat 8 mg Venglustat 15 mg
Hide Arm/Group Description:
All participants from Stage 1 or Stage 2 were randomized to receive placebo matched to venglustat once daily for treatment period of 24 months.
Participants from Stage 1 were randomized to receive venglustat 8 mg (i.e., 2 capsules of 4 mg) once daily for treatment period of 24 months.
All participants from Stage 1 or Stage 2 were randomized to receive 1 capsule of venglustat 15 mg once daily for treatment period of 24 months.
Overall Number of Participants Analyzed 200 78 199
Measure Type: Count of Participants
Unit of Measure: Participants
Sitting Systolic Blood Pressure: <=95 mmHg and decrease from Baseline >=20 mmHg Number Analyzed 196 participants 78 participants 196 participants
0
   0.0%
0
   0.0%
1
   0.5%
Sitting Systolic Blood Pressure: >=160 mmHg and increase from Baseline >=20 mmHg Number Analyzed 196 participants 78 participants 196 participants
2
   1.0%
3
   3.8%
10
   5.1%
Sitting Diastolic Blood Pressure: <= 45 mmHg and decrease from Baseline >=10 mmHg Number Analyzed 196 participants 78 participants 196 participants
0
   0.0%
0
   0.0%
0
   0.0%
Sitting Diastolic Blood Pressure: >=110 mmHg and increase from Baseline >=10 mmHg Number Analyzed 196 participants 78 participants 196 participants
2
   1.0%
4
   5.1%
7
   3.6%
Sitting Heart Rate: <=50 beats/min and decrease from Baseline >=20 beats/min Number Analyzed 196 participants 78 participants 196 participants
0
   0.0%
2
   2.6%
2
   1.0%
Sitting Heart Rate: >=120 beats/min and increase from Baseline >=20 beats/min Number Analyzed 196 participants 78 participants 196 participants
0
   0.0%
0
   0.0%
0
   0.0%
Weight: >=5% decrease from Baseline Number Analyzed 156 participants 70 participants 155 participants
11
   7.1%
4
   5.7%
13
   8.4%
Weight: >=5% increase from Baseline Number Analyzed 156 participants 70 participants 155 participants
15
   9.6%
9
  12.9%
15
   9.7%
17.Secondary Outcome
Title Number of Participants With Potentially Clinically Significant Abnormalities: Electrocardiogram: Combined Stage 1 and Stage 2
Hide Description Criteria for potentially clinically significant abnormalities: Heart Rate: <50 beats/minute; <50 beats/minute and decrease from Baseline >=20 beats/minute; <40 beats/minute; <40 beats/minute and decrease from Baseline >=20 beats/min; <30 beats/minute; >90 beats/minute; >90 beats/minute and increase from Baseline >=20 beats/minute; >100 beats/minute; >100 beats/minute and increase from Baseline >=20 beats/minute; >120 beats/minute; >120 beats/minute, increase from Baseline >=20 beats/minute; PR Interval: >200 milliseconds (msec); >200 msec and increase from Baseline >=25%; >220 msec, >240 msec; QRS Interval: >110 msec; >110 msec and increase from Baseline >=25%; >120 msec; >120 msec and increase from Baseline >=25%; QT Interval: >500 msec; QT corrected for heart rate (QTc) Bazett: >450 msec; >480 msec; increase from Baseline (30-60) msec; increase from Baseline >60 msec; QTc Fridericia: >450 msec; >480 msec; increase from Baseline (30-60) msec and increase from Baseline > 60 msec.
Time Frame From the first IMP administration up to the last IMP administration in EFC15392 study + 30 days (i.e., up to 25 months) or up to the first visit in LTS15823 study, whichever comes earlier
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on extended Combined Stage 1 and Stage 2 safety population. Here, "number analyzed" signifies participants with available data for each specified category. Data for this OM was planned to be collected and analyzed for combined Stage 1 and Stage 2 population as pre-specified in protocol.
Arm/Group Title Placebo Venglustat 8 mg Venglustat 15 mg
Hide Arm/Group Description:
All participants from Stage 1 or Stage 2 were randomized to receive placebo matched to venglustat once daily for treatment period of 24 months.
Participants from Stage 1 were randomized to receive venglustat 8 mg (i.e., 2 capsules of 4 mg) once daily for treatment period of 24 months.
All participants from Stage 1 or Stage 2 were randomized to receive 1 capsule of venglustat 15 mg once daily for treatment period of 24 months.
Overall Number of Participants Analyzed 200 78 199
Measure Type: Count of Participants
Unit of Measure: Participants
Heart Rate: <50 beats/min Number Analyzed 140 participants 70 participants 132 participants
7
   5.0%
6
   8.6%
13
   9.8%
Heart Rate: <50 beats/min and decrease from Baseline >=20 beats/min Number Analyzed 140 participants 70 participants 132 participants
1
   0.7%
0
   0.0%
1
   0.8%
Heart Rate: <40 beats/min Number Analyzed 140 participants 70 participants 132 participants
0
   0.0%
1
   1.4%
1
   0.8%
Heart Rate: <40 beats/min and decrease from Baseline >=20 beats/min Number Analyzed 140 participants 70 participants 132 participants
0
   0.0%
0
   0.0%
0
   0.0%
Heart Rate: <30 beats/min Number Analyzed 140 participants 70 participants 132 participants
0
   0.0%
0
   0.0%
0
   0.0%
Heart Rate: >90 beats/min Number Analyzed 140 participants 70 participants 132 participants
4
   2.9%
2
   2.9%
3
   2.3%
Heart Rate: >90 beats/min and increase from Baseline >=20 beats/min Number Analyzed 140 participants 70 participants 132 participants
2
   1.4%
2
   2.9%
2
   1.5%
Heart Rate: >100 beats/min Number Analyzed 140 participants 70 participants 132 participants
1
   0.7%
0
   0.0%
2
   1.5%
Heart Rate: >100 beats/min and increase from Baseline >=20 beats/min Number Analyzed 140 participants 70 participants 132 participants
1
   0.7%
0
   0.0%
1
   0.8%
Heart Rate: >120 beats/min Number Analyzed 140 participants 78 participants 132 participants
0
   0.0%
0
   0.0%
0
   0.0%
Heart Rate: >120 beats/min and increase from Baseline >=20 beats/min Number Analyzed 140 participants 70 participants 132 participants
0
   0.0%
0
   0.0%
0
   0.0%
PR Interval: >200 msec Number Analyzed 140 participants 70 participants 132 participants
8
   5.7%
2
   2.9%
10
   7.6%
PR Interval: >200 msec and increase from Baseline >=25% Number Analyzed 140 participants 70 participants 132 participants
0
   0.0%
0
   0.0%
0
   0.0%
PR Interval: >220 msec Number Analyzed 140 participants 70 participants 132 participants
1
   0.7%
0
   0.0%
2
   1.5%
PR Interval: >240 msec Number Analyzed 140 participants 70 participants 132 participants
0
   0.0%
0
   0.0%
0
   0.0%
QRS Interval: >110 msec Number Analyzed 140 participants 70 participants 132 participants
11
   7.9%
4
   5.7%
10
   7.6%
QRS Interval: > 110 msec and increase from Baseline >=25% Number Analyzed 140 participants 70 participants 132 participants
0
   0.0%
0
   0.0%
1
   0.8%
QRS Interval: >120 msec Number Analyzed 140 participants 70 participants 132 participants
2
   1.4%
1
   1.4%
3
   2.3%
QRS Interval: >120 msec and increase from Baseline >=25% Number Analyzed 140 participants 70 participants 132 participants
0
   0.0%
0
   0.0%
1
   0.8%
QT Interval: >500 msec Number Analyzed 140 participants 70 participants 132 participants
0
   0.0%
0
   0.0%
0
   0.0%
QTc Bazett: >450 msec Number Analyzed 140 participants 70 participants 132 participants
5
   3.6%
2
   2.9%
3
   2.3%
QTc Bazett: >480 msec Number Analyzed 140 participants 70 participants 132 participants
0
   0.0%
0
   0.0%
0
   0.0%
QTc Bazett: Increase from Baseline [30-60] msec Number Analyzed 136 participants 68 participants 128 participants
13
   9.6%
1
   1.5%
5
   3.9%
QTc Bazett: Increase from Baseline >60 msec Number Analyzed 136 participants 68 participants 128 participants
0
   0.0%
0
   0.0%
0
   0.0%
QTc Fridericia: >450 msec Number Analyzed 140 participants 70 participants 132 participants
4
   2.9%
1
   1.4%
2
   1.5%
QTc Fridericia: >480 msec Number Analyzed 140 participants 70 participants 132 participants
0
   0.0%
0
   0.0%
0
   0.0%
QTc Fridericia: Increase from Baseline [30-60] msec Number Analyzed 136 participants 68 participants 128 participants
5
   3.7%
1
   1.5%
3
   2.3%
QTc Fridericia: Increase from Baseline >60 msec Number Analyzed 136 participants 68 participants 128 participants
0
   0.0%
0
   0.0%
0
   0.0%
18.Secondary Outcome
Title Number of Participants With Physical Examination Abnormalities: Combined Stage 1 and Stage 2
Hide Description Physical examination included: Head, Heart, Lung, Abdomen, Musculo/Skeletal, Skin, and Mental Status. Abnormality in physical examination was based on investigator's discretion. Results are based on the treatment emergent period which was defined as time from the first IMP administration up to the last IMP administration in EFC15392 study + 30 days or up to the first visit in LTS15823 study, whichever comes earlier.
Time Frame Baseline, Month 18, Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on extended Combined Stage 1 and Stage 2 safety population. Here, "number analyzed" signifies participants with available data for each specified category. Data for this OM was planned to be collected and analyzed for combined Stage 1 and Stage 2 population as pre-specified in protocol.
Arm/Group Title Placebo Venglustat 8 mg Venglustat 15 mg
Hide Arm/Group Description:
All participants from Stage 1 or Stage 2 were randomized to receive placebo matched to venglustat once daily for treatment period of 24 months.
Participants from Stage 1 were randomized to receive venglustat 8 mg (i.e., 2 capsules of 4 mg) once daily for treatment period of 24 months.
All participants from Stage 1 or Stage 2 were randomized to receive 1 capsule of venglustat 15 mg once daily for treatment period of 24 months.
Overall Number of Participants Analyzed 200 78 199
Measure Type: Count of Participants
Unit of Measure: Participants
Baseline: Head Number Analyzed 200 participants 78 participants 198 participants
1
   0.5%
1
   1.3%
4
   2.0%
Baseline: Heart Number Analyzed 200 participants 78 participants 198 participants
2
   1.0%
1
   1.3%
1
   0.5%
Baseline: Lung Number Analyzed 200 participants 78 participants 198 participants
0
   0.0%
0
   0.0%
0
   0.0%
Baseline: Abdomen Number Analyzed 200 participants 78 participants 198 participants
15
   7.5%
12
  15.4%
24
  12.1%
Baseline: Musculo/Skeletal Number Analyzed 199 participants 78 participants 198 participants
5
   2.5%
1
   1.3%
4
   2.0%
Baseline: Skin Number Analyzed 199 participants 78 participants 198 participants
7
   3.5%
2
   2.6%
3
   1.5%
Baseline: Mental Status Number Analyzed 200 participants 78 participants 198 participants
0
   0.0%
0
   0.0%
0
   0.0%
Month 18: Head Number Analyzed 49 participants 49 participants 47 participants
0
   0.0%
0
   0.0%
1
   2.1%
Month 18: Heart Number Analyzed 49 participants 49 participants 47 participants
0
   0.0%
0
   0.0%
1
   2.1%
Month 18: Lung Number Analyzed 49 participants 49 participants 47 participants
0
   0.0%
0
   0.0%
0
   0.0%
Month 18: Abdomen Number Analyzed 49 participants 49 participants 47 participants
2
   4.1%
1
   2.0%
0
   0.0%
Month 18: Musculo/Skeletal Number Analyzed 49 participants 49 participants 47 participants
0
   0.0%
0
   0.0%
1
   2.1%
Month 18: Skin Number Analyzed 49 participants 49 participants 47 participants
1
   2.0%
1
   2.0%
0
   0.0%
Month 18: Mental Status Number Analyzed 49 participants 49 participants 47 participants
1
   2.0%
0
   0.0%
0
   0.0%
Month 24: Head Number Analyzed 7 participants 4 participants 7 participants
0
   0.0%
0
   0.0%
0
   0.0%
Month 24: Heart Number Analyzed 7 participants 4 participants 7 participants
0
   0.0%
0
   0.0%
0
   0.0%
Month 24: Lung Number Analyzed 7 participants 4 participants 7 participants
0
   0.0%
0
   0.0%
0
   0.0%
Month 24: Abdomen Number Analyzed 7 participants 4 participants 7 participants
0
   0.0%
0
   0.0%
0
   0.0%
Month 24: Musculo/Skeletal Number Analyzed 7 participants 4 participants 7 participants
0
   0.0%
0
   0.0%
0
   0.0%
Month 24: Skin Number Analyzed 7 participants 4 participants 7 participants
0
   0.0%
0
   0.0%
0
   0.0%
Month 24: Mental Status Number Analyzed 7 participants 4 participants 7 participants
0
   0.0%
0
   0.0%
0
   0.0%
19.Secondary Outcome
Title Change From Baseline in Beck Depression Inventory-II (BDI-II) Score: Combined Stage 1 and Stage 2
Hide Description The Beck Depression Inventory-II (BDI-II) is a 21-item questionnaire used to assess depression. Most items are rated on a 4-point scale from 0 to 3, and a few items are rated on a 7-point scale. Individual item scores are added to get a total BDI-II score from 0 to 63. The higher the total score, the more severe the depression, and the lower the total score, the less severe the depression.
Time Frame Baseline, Months 3, 6, 9, 12, 15, 18, 21, and 24, Last on-treatment value up to last IMP + 1 day (anytime during the maximum duration of 25 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on extended Combined Stage 1 and Stage 2 safety population. Here, "number analyzed" signifies participants with available data for each specified category. Data for this OM was planned to be collected and analyzed for combined Stage 1 and Stage 2 population as pre-specified in protocol.
Arm/Group Title Placebo Venglustat 8 mg Venglustat 15 mg
Hide Arm/Group Description:
All participants from Stage 1 or Stage 2 were randomized to receive placebo matched to venglustat once daily for treatment period of 24 months.
Participants from Stage 1 were randomized to receive venglustat 8 mg (i.e., 2 capsules of 4 mg) once daily for treatment period of 24 months.
All participants from Stage 1 or Stage 2 were randomized to receive 1 capsule of venglustat 15 mg once daily for treatment period of 24 months.
Overall Number of Participants Analyzed 200 78 199
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 191 participants 77 participants 194 participants
4.0  (4.7) 3.0  (4.1) 3.4  (4.1)
Change at Month 3 Number Analyzed 147 participants 73 participants 153 participants
-0.1  (4.0) 0.7  (4.0) 0.7  (4.3)
Change at Month 6 Number Analyzed 122 participants 68 participants 128 participants
-0.6  (4.2) 0.9  (4.2) 0.3  (3.9)
Change at Month 9 Number Analyzed 92 participants 67 participants 100 participants
-0.3  (4.8) 0.1  (3.7) 0.7  (4.9)
Change at Month 12 Number Analyzed 58 participants 61 participants 63 participants
-1.9  (3.9) 0.2  (4.7) 1.5  (5.3)
Change at Month 15 Number Analyzed 54 participants 56 participants 54 participants
-1.5  (4.4) -0.1  (4.4) -0.3  (4.0)
Change at Month 18 Number Analyzed 42 participants 46 participants 43 participants
-1.0  (4.9) 0.5  (3.0) 0.0  (3.5)
Change at Month 21 Number Analyzed 24 participants 28 participants 32 participants
1.0  (9.5) -0.1  (1.3) 1.1  (2.8)
Change at Month 24 Number Analyzed 4 participants 4 participants 7 participants
-0.3  (0.5) 0.8  (2.2) 0.3  (1.7)
Change at Last on-treatment value Number Analyzed 155 participants 74 participants 164 participants
-0.5  (5.1) 0.1  (4.0) 0.3  (4.6)
20.Secondary Outcome
Title Number of Participants With Worsening Lens Opacity From Baseline During the Treatment-emergent Period: Combined Stage 1 and Stage 2
Hide Description Worsening of lens opacity classification system (LOCS) III score or World Health Organization (WHO) grade in nuclear opacification, cortical opacification and posterior subcapsular opacification were assessed for 'Any eye', 'Unilateral' and 'Bilateral' separately. A participant could be counted in all the 3 categories. In each category, the worst case was taken into account. To be evaluable for 'Any', a participant had to have at least one eye evaluable, whereas, for 'Unilateral' and 'Bilateral', a participant had to have both eyes evaluable. Therefore, the sum of 'Unilateral' + 'Bilateral' is not necessarily equal to 'Any' in the below table. The difference observed in 'Nuclear Opacification' in 15 mg group, comes from that 1 participant who had Unilateral worsening at a given visit and a Bilateral worsening at another visit. Therefore, this participant was counted as 'Unilateral', 'Bilateral' and counted only once in 'Any'. Results are based on the TE period.
Time Frame From the first IMP administration up to the last IMP administration in EFC15392 study + 30 days (i.e., up to 25 months) or up to the first visit in LTS15823 study, whichever comes earlier
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on extended Combined Stage 1 and Stage 2 safety population. Here, "number analyzed" signifies participants with available data for each specified category. Data for this OM was planned to be collected and analyzed for combined Stage 1 and Stage 2 population as pre-specified in protocol. TE period: time from first IMP administration up to the last IMP administration in EFC15392 study + 30 days or up to the first visit in LTS15823 study, whichever comes earlier.
Arm/Group Title Placebo Venglustat 8 mg Venglustat 15 mg
Hide Arm/Group Description:
All participants from Stage 1 or Stage 2 were randomized to receive placebo matched to venglustat once daily for treatment period of 24 months.
Participants from Stage 1 were randomized to receive venglustat 8 mg (i.e., 2 capsules of 4 mg) once daily for treatment period of 24 months.
All participants from Stage 1 or Stage 2 were randomized to receive 1 capsule of venglustat 15 mg once daily for treatment period of 24 months.
Overall Number of Participants Analyzed 200 78 199
Measure Type: Count of Participants
Unit of Measure: Participants
Worsening of LOCS III score >= 0.5 or WHO grade >= 1.0 in nuclear opacification: Any eye Number Analyzed 91 participants 61 participants 98 participants
8
   8.8%
3
   4.9%
9
   9.2%
Worsening of LOCS III score >= 0.5 or WHO grade >= 1.0 in nuclear opacification: Unilateral Number Analyzed 91 participants 61 participants 98 participants
0
   0.0%
0
   0.0%
4
   4.1%
Worsening of LOCS III score >= 0.5 or WHO grade >= 1.0 in nuclear opacification: Bilateral Number Analyzed 91 participants 61 participants 98 participants
8
   8.8%
3
   4.9%
6
   6.1%
Worsening of LOCS III score >= 0.8 or WHO grade >= 1.0 in cortical opacification: Any eye Number Analyzed 84 participants 61 participants 87 participants
4
   4.8%
4
   6.6%
4
   4.6%
Worsening of LOCS III score >= 0.8 or WHO grade >= 1.0 in cortical opacification: Unilateral Number Analyzed 83 participants 61 participants 87 participants
1
   1.2%
0
   0.0%
1
   1.1%
Worsening of LOCS III score >= 0.8 or WHO grade >= 1.0 in cortical opacification: Bilateral Number Analyzed 83 participants 61 participants 87 participants
2
   2.4%
4
   6.6%
3
   3.4%
Worsening of LOCS III score>=0.5 or WHO grade >= 1.0 in posterior subcapsular opacification:Any eye Number Analyzed 81 participants 56 participants 87 participants
2
   2.5%
2
   3.6%
3
   3.4%
Worsening of LOCS III score>=0.5 or WHO grade >=1.0 in posterior subcapsularopacification:Unilateral Number Analyzed 81 participants 56 participants 87 participants
0
   0.0%
1
   1.8%
1
   1.1%
Worsening of LOCS III score>=0.5 or WHO grade >=1.0 in posterior subcapsular opacification:Bilateral Number Analyzed 81 participants 56 participants 87 participants
2
   2.5%
1
   1.8%
2
   2.3%
Time Frame From the first IMP administration up to the last IMP administration in EFC15392 study + 30 days (i.e., up to 25 months) or up to the first visit in LTS15823 study, whichever comes earlier
Adverse Event Reporting Description Reported AEs were TEAEs that developed/worsened in grade or became serious during TE period (time from the first IMP administration up to the last IMP administration in EFC15392 study + 30 days or up to the first visit in LTS15823 study, whichever comes earlier). Analysis was performed on the Stage 1 and Stage 2 safety population.
 
Arm/Group Title Stage 1- Placebo Stage 1- Venglustat 8 mg Stage 1- Venglustat 15 mg Stage 2- Placebo Stage 2- Venglustat 15 mg
Hide Arm/Group Description Participants from Stage 1 were randomized to receive 2 capsules of placebo matched to venglustat once daily for treatment period of 24 months. Participants from Stage 1 were randomized to receive venglustat 8 mg (i.e., 2 capsules of 4 mg) once daily for treatment period of 24 months. Participants from Stage 1 were randomized to receive 1 capsule of venglustat 15 mg and 1 capsule of placebo matched to venglustat once daily for treatment period of 24 months. Participants from Stage 2 were randomized to receive 1 capsule of placebo matched to venglustat once daily for treatment period of 24 months. Participants from Stage 2 were randomized to receive 1 capsule of venglustat 15 mg once daily for treatment period of 24 months.
All-Cause Mortality
Stage 1- Placebo Stage 1- Venglustat 8 mg Stage 1- Venglustat 15 mg Stage 2- Placebo Stage 2- Venglustat 15 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/78 (0.00%)      0/78 (0.00%)      0/80 (0.00%)      0/122 (0.00%)      0/119 (0.00%)    
Hide Serious Adverse Events
Stage 1- Placebo Stage 1- Venglustat 8 mg Stage 1- Venglustat 15 mg Stage 2- Placebo Stage 2- Venglustat 15 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/78 (10.26%)      15/78 (19.23%)      19/80 (23.75%)      6/122 (4.92%)      7/119 (5.88%)    
Cardiac disorders           
Arteriosclerosis Coronary Artery  1  0/78 (0.00%)  0 0/78 (0.00%)  0 0/80 (0.00%)  0 1/122 (0.82%)  1 0/119 (0.00%)  0
Coronary Artery Stenosis  1  0/78 (0.00%)  0 1/78 (1.28%)  2 0/80 (0.00%)  0 0/122 (0.00%)  0 0/119 (0.00%)  0
Mitral Valve Incompetence  1  0/78 (0.00%)  0 0/78 (0.00%)  0 0/80 (0.00%)  0 1/122 (0.82%)  2 0/119 (0.00%)  0
Supraventricular Tachycardia  1  0/78 (0.00%)  0 0/78 (0.00%)  0 0/80 (0.00%)  0 1/122 (0.82%)  1 0/119 (0.00%)  0
Gastrointestinal disorders           
Dental Cyst  1  0/78 (0.00%)  0 0/78 (0.00%)  0 1/80 (1.25%)  1 0/122 (0.00%)  0 0/119 (0.00%)  0
Inguinal Hernia  1  0/78 (0.00%)  0 0/78 (0.00%)  0 0/80 (0.00%)  0 1/122 (0.82%)  1 0/119 (0.00%)  0
Large Intestinal Stenosis  1  0/78 (0.00%)  0 0/78 (0.00%)  0 1/80 (1.25%)  1 0/122 (0.00%)  0 0/119 (0.00%)  0
Pancreatitis Acute  1  0/78 (0.00%)  0 0/78 (0.00%)  0 0/80 (0.00%)  0 0/122 (0.00%)  0 1/119 (0.84%)  1
Rectal Haemorrhage  1  0/78 (0.00%)  0 1/78 (1.28%)  1 0/80 (0.00%)  0 0/122 (0.00%)  0 0/119 (0.00%)  0
General disorders           
Haemorrhagic Cyst  1  0/78 (0.00%)  0 0/78 (0.00%)  0 1/80 (1.25%)  1 0/122 (0.00%)  0 0/119 (0.00%)  0
Non-Cardiac Chest Pain  1  0/78 (0.00%)  0 0/78 (0.00%)  0 1/80 (1.25%)  1 0/122 (0.00%)  0 0/119 (0.00%)  0
Hepatobiliary disorders           
Hepatic Pain  1  1/78 (1.28%)  1 0/78 (0.00%)  0 0/80 (0.00%)  0 0/122 (0.00%)  0 0/119 (0.00%)  0
Infections and infestations           
Appendicitis  1  1/78 (1.28%)  1 1/78 (1.28%)  1 2/80 (2.50%)  2 0/122 (0.00%)  0 0/119 (0.00%)  0
Covid-19  1  0/78 (0.00%)  0 0/78 (0.00%)  0 0/80 (0.00%)  0 2/122 (1.64%)  2 0/119 (0.00%)  0
Diverticulitis  1  0/78 (0.00%)  0 1/78 (1.28%)  1 1/80 (1.25%)  1 0/122 (0.00%)  0 0/119 (0.00%)  0
Gastroenteritis Viral  1  0/78 (0.00%)  0 1/78 (1.28%)  1 0/80 (0.00%)  0 0/122 (0.00%)  0 0/119 (0.00%)  0
Infected Cyst  1  0/78 (0.00%)  0 0/78 (0.00%)  0 1/80 (1.25%)  1 0/122 (0.00%)  0 0/119 (0.00%)  0
Influenza  1  0/78 (0.00%)  0 1/78 (1.28%)  1 0/80 (0.00%)  0 0/122 (0.00%)  0 0/119 (0.00%)  0
Kidney Infection  1  0/78 (0.00%)  0 0/78 (0.00%)  0 1/80 (1.25%)  2 0/122 (0.00%)  0 0/119 (0.00%)  0
Pneumonia  1  0/78 (0.00%)  0 0/78 (0.00%)  0 1/80 (1.25%)  1 0/122 (0.00%)  0 0/119 (0.00%)  0
Renal Cyst Infection  1  0/78 (0.00%)  0 3/78 (3.85%)  3 1/80 (1.25%)  1 0/122 (0.00%)  0 1/119 (0.84%)  1
Urinary Tract Infection  1  1/78 (1.28%)  1 0/78 (0.00%)  0 2/80 (2.50%)  2 0/122 (0.00%)  0 0/119 (0.00%)  0
Injury, poisoning and procedural complications           
Back Injury  1  0/78 (0.00%)  0 1/78 (1.28%)  1 0/80 (0.00%)  0 0/122 (0.00%)  0 0/119 (0.00%)  0
Hand Fracture  1  0/78 (0.00%)  0 0/78 (0.00%)  0 1/80 (1.25%)  1 0/122 (0.00%)  0 0/119 (0.00%)  0
Jaw Fracture  1  0/78 (0.00%)  0 0/78 (0.00%)  0 1/80 (1.25%)  1 0/122 (0.00%)  0 0/119 (0.00%)  0
Subdural Haematoma  1  1/78 (1.28%)  1 0/78 (0.00%)  0 0/80 (0.00%)  0 0/122 (0.00%)  0 0/119 (0.00%)  0
Tibia Fracture  1  0/78 (0.00%)  0 0/78 (0.00%)  0 0/80 (0.00%)  0 1/122 (0.82%)  1 0/119 (0.00%)  0
Metabolism and nutrition disorders           
Fluid Overload  1  0/78 (0.00%)  0 0/78 (0.00%)  0 1/80 (1.25%)  1 0/122 (0.00%)  0 0/119 (0.00%)  0
Hyperkalaemia  1  0/78 (0.00%)  0 0/78 (0.00%)  0 1/80 (1.25%)  1 0/122 (0.00%)  0 0/119 (0.00%)  0
Musculoskeletal and connective tissue disorders           
Flank Pain  1  1/78 (1.28%)  1 0/78 (0.00%)  0 0/80 (0.00%)  0 0/122 (0.00%)  0 0/119 (0.00%)  0
Osteoarthritis  1  0/78 (0.00%)  0 1/78 (1.28%)  1 0/80 (0.00%)  0 0/122 (0.00%)  0 0/119 (0.00%)  0
Rotator Cuff Syndrome  1  1/78 (1.28%)  1 0/78 (0.00%)  0 0/80 (0.00%)  0 0/122 (0.00%)  0 0/119 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Basal Cell Carcinoma  1  1/78 (1.28%)  1 0/78 (0.00%)  0 0/80 (0.00%)  0 0/122 (0.00%)  0 0/119 (0.00%)  0
Breast Cancer  1  0/78 (0.00%)  0 1/78 (1.28%)  1 0/80 (0.00%)  0 0/122 (0.00%)  0 0/119 (0.00%)  0
Intraductal Proliferative Breast Lesion  1  0/78 (0.00%)  0 0/78 (0.00%)  0 0/80 (0.00%)  0 0/122 (0.00%)  0 1/119 (0.84%)  1
Invasive Ductal Breast Carcinoma  1  0/78 (0.00%)  0 0/78 (0.00%)  0 0/80 (0.00%)  0 0/122 (0.00%)  0 1/119 (0.84%)  1
Mediastinum Neoplasm  1  0/78 (0.00%)  0 0/78 (0.00%)  0 0/80 (0.00%)  0 0/122 (0.00%)  0 1/119 (0.84%)  1
Nervous system disorders           
Carpal Tunnel Syndrome  1  0/78 (0.00%)  0 0/78 (0.00%)  0 1/80 (1.25%)  1 0/122 (0.00%)  0 0/119 (0.00%)  0
Intracranial Aneurysm  1  0/78 (0.00%)  0 0/78 (0.00%)  0 1/80 (1.25%)  1 0/122 (0.00%)  0 0/119 (0.00%)  0
Loss Of Consciousness  1  0/78 (0.00%)  0 0/78 (0.00%)  0 0/80 (0.00%)  0 0/122 (0.00%)  0 1/119 (0.84%)  1
Polyneuropathy  1  0/78 (0.00%)  0 0/78 (0.00%)  0 1/80 (1.25%)  1 0/122 (0.00%)  0 0/119 (0.00%)  0
Syncope  1  0/78 (0.00%)  0 0/78 (0.00%)  0 1/80 (1.25%)  1 0/122 (0.00%)  0 0/119 (0.00%)  0
Psychiatric disorders           
Depression  1  0/78 (0.00%)  0 0/78 (0.00%)  0 1/80 (1.25%)  1 0/122 (0.00%)  0 0/119 (0.00%)  0
Suicidal Ideation  1  0/78 (0.00%)  0 0/78 (0.00%)  0 1/80 (1.25%)  1 0/122 (0.00%)  0 0/119 (0.00%)  0
Renal and urinary disorders           
Acute Kidney Injury  1  0/78 (0.00%)  0 1/78 (1.28%)  1 0/80 (0.00%)  0 0/122 (0.00%)  0 0/119 (0.00%)  0
Calculus Urinary  1  0/78 (0.00%)  0 0/78 (0.00%)  0 0/80 (0.00%)  0 0/122 (0.00%)  0 1/119 (0.84%)  1
Chronic Kidney Disease  1  1/78 (1.28%)  1 0/78 (0.00%)  0 0/80 (0.00%)  0 0/122 (0.00%)  0 0/119 (0.00%)  0
Haematuria  1  0/78 (0.00%)  0 3/78 (3.85%)  3 0/80 (0.00%)  0 0/122 (0.00%)  0 0/119 (0.00%)  0
Renal Cyst Haemorrhage  1  0/78 (0.00%)  0 0/78 (0.00%)  0 0/80 (0.00%)  0 0/122 (0.00%)  0 2/119 (1.68%)  2
Renal Cyst Ruptured  1  0/78 (0.00%)  0 2/78 (2.56%)  2 0/80 (0.00%)  0 0/122 (0.00%)  0 0/119 (0.00%)  0
Renal Haemorrhage  1  0/78 (0.00%)  0 0/78 (0.00%)  0 1/80 (1.25%)  2 0/122 (0.00%)  0 0/119 (0.00%)  0
Ureterolithiasis  1  0/78 (0.00%)  0 1/78 (1.28%)  1 0/80 (0.00%)  0 0/122 (0.00%)  0 0/119 (0.00%)  0
Reproductive system and breast disorders           
Adenomyosis  1  0/78 (0.00%)  0 0/78 (0.00%)  0 1/80 (1.25%)  1 0/122 (0.00%)  0 0/119 (0.00%)  0
Skin and subcutaneous tissue disorders           
Rash  1  1/78 (1.28%)  1 0/78 (0.00%)  0 0/80 (0.00%)  0 0/122 (0.00%)  0 0/119 (0.00%)  0
1
Term from vocabulary, MedDRA 24.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Stage 1- Placebo Stage 1- Venglustat 8 mg Stage 1- Venglustat 15 mg Stage 2- Placebo Stage 2- Venglustat 15 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   42/78 (53.85%)      46/78 (58.97%)      48/80 (60.00%)      32/122 (26.23%)      48/119 (40.34%)    
Eye disorders           
Cataract Cortical  1  5/78 (6.41%)  5 2/78 (2.56%)  4 3/80 (3.75%)  3 1/122 (0.82%)  1 2/119 (1.68%)  2
Cataract Nuclear  1  5/78 (6.41%)  5 2/78 (2.56%)  2 3/80 (3.75%)  4 1/122 (0.82%)  1 2/119 (1.68%)  2
Dry Eye  1  5/78 (6.41%)  5 0/78 (0.00%)  0 2/80 (2.50%)  2 1/122 (0.82%)  1 0/119 (0.00%)  0
Gastrointestinal disorders           
Constipation  1  0/78 (0.00%)  0 4/78 (5.13%)  4 3/80 (3.75%)  3 0/122 (0.00%)  0 8/119 (6.72%)  8
Diarrhoea  1  2/78 (2.56%)  4 0/78 (0.00%)  0 6/80 (7.50%)  6 3/122 (2.46%)  3 2/119 (1.68%)  2
Dyspepsia  1  4/78 (5.13%)  5 1/78 (1.28%)  1 0/80 (0.00%)  0 1/122 (0.82%)  1 2/119 (1.68%)  2
Nausea  1  1/78 (1.28%)  1 6/78 (7.69%)  6 7/80 (8.75%)  9 0/122 (0.00%)  0 6/119 (5.04%)  6
General disorders           
Fatigue  1  1/78 (1.28%)  1 4/78 (5.13%)  5 9/80 (11.25%)  9 3/122 (2.46%)  3 2/119 (1.68%)  2
Influenza Like Illness  1  1/78 (1.28%)  1 5/78 (6.41%)  5 1/80 (1.25%)  1 1/122 (0.82%)  2 0/119 (0.00%)  0
Infections and infestations           
Covid-19  1  5/78 (6.41%)  5 6/78 (7.69%)  6 1/80 (1.25%)  1 3/122 (2.46%)  3 7/119 (5.88%)  7
Conjunctivitis  1  4/78 (5.13%)  5 0/78 (0.00%)  0 1/80 (1.25%)  1 1/122 (0.82%)  1 1/119 (0.84%)  1
Influenza  1  4/78 (5.13%)  4 3/78 (3.85%)  3 0/80 (0.00%)  0 1/122 (0.82%)  1 0/119 (0.00%)  0
Nasopharyngitis  1  10/78 (12.82%)  13 5/78 (6.41%)  5 6/80 (7.50%)  9 2/122 (1.64%)  2 0/119 (0.00%)  0
Upper Respiratory Tract Infection  1  0/78 (0.00%)  0 4/78 (5.13%)  4 6/80 (7.50%)  8 4/122 (3.28%)  4 6/119 (5.04%)  7
Urinary Tract Infection  1  6/78 (7.69%)  6 5/78 (6.41%)  6 7/80 (8.75%)  15 3/122 (2.46%)  4 1/119 (0.84%)  1
Musculoskeletal and connective tissue disorders           
Arthralgia  1  4/78 (5.13%)  4 3/78 (3.85%)  3 2/80 (2.50%)  2 2/122 (1.64%)  2 2/119 (1.68%)  2
Back Pain  1  8/78 (10.26%)  9 6/78 (7.69%)  7 8/80 (10.00%)  8 5/122 (4.10%)  5 2/119 (1.68%)  2
Flank Pain  1  3/78 (3.85%)  3 1/78 (1.28%)  1 5/80 (6.25%)  5 1/122 (0.82%)  1 0/119 (0.00%)  0
Pain In Extremity  1  0/78 (0.00%)  0 4/78 (5.13%)  4 0/80 (0.00%)  0 1/122 (0.82%)  1 0/119 (0.00%)  0
Nervous system disorders           
Dizziness  1  2/78 (2.56%)  2 4/78 (5.13%)  4 4/80 (5.00%)  4 2/122 (1.64%)  2 3/119 (2.52%)  3
Headache  1  6/78 (7.69%)  6 8/78 (10.26%)  9 11/80 (13.75%)  14 7/122 (5.74%)  8 8/119 (6.72%)  8
Renal and urinary disorders           
Haematuria  1  3/78 (3.85%)  3 4/78 (5.13%)  5 0/80 (0.00%)  0 4/122 (3.28%)  5 2/119 (1.68%)  2
Respiratory, thoracic and mediastinal disorders           
Cough  1  1/78 (1.28%)  1 5/78 (6.41%)  8 8/80 (10.00%)  8 1/122 (0.82%)  1 7/119 (5.88%)  8
Vascular disorders           
Hypertension  1  2/78 (2.56%)  2 5/78 (6.41%)  5 7/80 (8.75%)  7 4/122 (3.28%)  4 4/119 (3.36%)  4
1
Term from vocabulary, MedDRA 24.0
Indicates events were collected by systematic assessment
Following decision to discontinue EFC15392 based on the futility analysis, the two-steps analysis initially planned were not applicable, therefore only the final analysis of all safety endpoints (laboratory, vital sign, ECG, physical examination, BDI-II, and lens opacity) were performed on extended combined Stage 1 and Stage 2 safety population only.
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 Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Trial Transparency Team
Organization: Sanofi aventis recherche & développement
Phone: 800-633-1610 ext 6#
EMail: Contact-US@sanofi.com
Layout table for additonal information
Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT03523728    
Other Study ID Numbers: EFC15392
2017-004084-12 ( EudraCT Number )
U1111-1202-0775 ( Other Identifier: UTN )
First Submitted: May 1, 2018
First Posted: May 14, 2018
Results First Submitted: July 29, 2022
Results First Posted: November 9, 2022
Last Update Posted: November 9, 2022