A Phase 2/3 interventional study of Venglustat and Placebo in Polycystic Kidney, Autosomal Dominant, sponsored by Genzyme, a Sanofi Company. Terminated at 95 sites in 23 countries. Open to participants aged 18 Years to 55 Years. Per ClinicalTrials.gov, last updated 2023-02-03.
Sponsored by Genzyme, a Sanofi Company · Phase 2/3, Interventional, and Treatment
Primary Objective:
To determine the effect of venglustat on the rate of total kidney volume (TKV) growth (Stage 1) and estimated glomerular filtration rate (eGFR) decline in participants at risk of rapidly progressive Autosomal Dominant Polycystic Kidney Disease (ADPKD) (Stage 2).
Secondary Objectives:
Study duration per participant was 26 months (maximal) that included a screening period of 15 days, run-in period of 2 weeks, a 24-month treatment period, and a follow-up 30 days after final dose of investigational medicinal product (IMP).
158 studies on the registry are indexed under Polycystic Kidney Diseases; 21 are open to participants now.
This study's enrollment of 478 is above the median of 46 across 115 interventional studies indexed under Polycystic Kidney Diseases.
Browse Polycystic Kidney Diseases studies →Genzyme, a Sanofi Company is the lead sponsor of 303 studies on the registry; 5 are open to participants now.
Of its 24 completed or terminated interventional studies of FDA-regulated products, 19 (79%) have results posted.
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Male or female adult with ADPKD with age at the time the consent was signed:
Mayo Imaging Classification of ADPKD Class 1C, 1D or 1E**
**Total kidney volume (TKV) had confirmed by a central reader prior to Visit 3.
Estimated glomerular filtration rate between 30 to 89.9 mL/min/1.73 m\^2 during screening period* (CKD-EPI equation) for Stage 2.
*Eligibility would be confirmed by eGFR value from one of the two first pre-randomization eGFR measurements.
Exclusion criteria:
The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Participants from Stage 1 were randomized to receive 2 capsules of placebo matched to venglustat once daily for treatment period of 24 months.
Drug: Placebo
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.
Drug: Venglustat
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.
Drug: Venglustat · Drug: Placebo
Participants from Stage 2 were randomized to receive 1 capsule of placebo matched to venglustat once daily for treatment period of 24 months.
Drug: Placebo
Participants from Stage 2 were randomized to receive 1 capsule of venglustat 15 mg once daily for treatment period of 24 months.
Drug: Venglustat
Pharmaceutical form: capsule; Route of administration: oral
Also known as: GZ402671
Pharmaceutical form: capsule; Route of administration: oral
Annualized Slope of Change in Total Kidney Volume (TKV) From Baseline to Month 18: Stage 1
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
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
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
Annualized Rate of Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Month 24: Stage 1
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
Annualized Slope of Change in Total Kidney Volume (TKV) From Baseline to Month 18: Combined Stage 1 and Stage 2
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
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
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
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
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
Change in Fatigue Severity as Measured by Brief Fatigue Inventory (BFI-SF)-Item 3 Scale Score From Baseline to Month 18: Stage 1
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
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
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
Pharmacokinetics: Plasma Concentration of Venglustat: Stage 1
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
Pharmacokinetics: Plasma Concentration of Venglustat: Stage 2
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
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs): Stage 1
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
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs): Combined Stage 1 and Stage 2
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
Number of Participants With Potentially Clinically Significant Abnormalities: Hematology: Combined Stage 1 and Stage 2
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
Number of Participants With Potentially Clinically Significant Abnormalities: Clinical Chemistry: Combined Stage 1 and Stage 2
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
Number of Participants With Potentially and Clinically Significant Abnormalities: Urinalysis: Combined Stage 1 and Stage 2
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
Number of Participants With Potentially and Clinically Significant Abnormalities: Vital Signs: Combined Stage 1 and Stage 2
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
Number of Participants With Potentially Clinically Significant Abnormalities: Electrocardiogram: Combined Stage 1 and Stage 2
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
Number of Participants With Physical Examination Abnormalities: Combined Stage 1 and Stage 2
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
Change From Baseline in Beck Depression Inventory-II (BDI-II) Score: Combined Stage 1 and Stage 2
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)
Number of Participants With Worsening Lens Opacity From Baseline During the Treatment-emergent Period: Combined Stage 1 and Stage 2
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
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.
| Milestone | Stage 1- Placebo | Stage 1- Venglustat 8 mg | Stage 1- Venglustat 15 mg | Stage 2- Placebo | Stage 2- Venglustat 15 mg |
|---|---|---|---|---|---|
| Started | 78 | 78 | 80 | 0 | 0 |
| Completed | 12 | 10 | 12 | 0 | 0 |
| Not completed | 66 | 68 | 68 | 0 | 0 |
| Withdrew: Adverse event | 2 | 2 | 4 | 0 | 0 |
| Withdrew: Progressive disease | 0 | 0 | 1 | 0 | 0 |
| Withdrew: Lack of efficacy | 2 | 0 | 0 | 0 | 0 |
| Withdrew: Poor compliance to protocol | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Withdrawal by subject | 6 | 5 | 7 | 0 | 0 |
| Withdrew: Study terminated by sponsor | 54 | 59 | 56 | 0 | 0 |
| Withdrew: Other-unspecified | 1 | 2 | 0 | 0 | 0 |
| Milestone | Stage 1- Placebo | Stage 1- Venglustat 8 mg | Stage 1- Venglustat 15 mg | Stage 2- Placebo | Stage 2- Venglustat 15 mg |
|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 123 | 119 |
| 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 |
| Withdrew: Adverse event | 0 | 0 | 0 | 1 | 2 |
| Withdrew: Withdrawal by subject | 0 | 0 | 0 | 0 | 4 |
| Withdrew: Study terminated by sponsor | 0 | 0 | 0 | 119 | 110 |
| Withdrew: Other-unspecified | 0 | 0 | 0 | 2 | 3 |
| Withdrew: Randomized and not treated | 0 | 0 | 0 | 1 | 0 |
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.
| percent change in TKV/year | Stage 1- Placebo | Stage 1- Venglustat 8 mg | Stage 1- Venglustat 15 mg |
|---|---|---|---|
| Annualized Slope of Change in Total Kidney Volume (TKV) From Baseline to Month 18: Stage 1 | 6.35 (5.10 to 7.62) | 7.71 (6.46 to 8.98) | 6.38 (5.11 to 7.66) |
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.
| mL/min/1.73 m^2/year | Placebo | Venglustat 8 mg | Venglustat 15 mg |
|---|---|---|---|
| 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 | -2.40 (-3.30 to -1.49) | -4.82 (-5.82 to -3.83) | -4.89 (-5.80 to -3.99) |
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.
| mL/min/1.73 m^2/year | Stage 1- Placebo | Stage 1- Venglustat 8 mg | Stage 1- Venglustat 15 mg |
|---|---|---|---|
| Annualized Rate of Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Month 24: Stage 1 | -3.14 (-4.09 to -2.18) | -4.74 (-5.68 to -3.80) | -4.59 (-5.53 to -3.65) |
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.
No measurements were reported for this outcome.
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.
| score on a scale | Stage 1- Placebo | Stage 1- Venglustat 8 mg | Stage 1- Venglustat 15 mg |
|---|---|---|---|
| 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 | -0.09 ± 0.15 | 0.01 ± 0.17 | -0.35 ± 0.16 |
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.
| score on a scale | Placebo | Venglustat 8 mg | Venglustat 15 mg |
|---|---|---|---|
| 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 | -0.20 ± 0.23 | -0.31 ± 0.36 | -0.36 ± 0.23 |
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.
| score on a scale | Stage 1- Placebo | Stage 1- Venglustat 8 mg | Stage I- Venglustat 15 mg |
|---|---|---|---|
| Change in Fatigue Severity as Measured by Brief Fatigue Inventory (BFI-SF)-Item 3 Scale Score From Baseline to Month 18: Stage 1 | -0.26 ± 0.23 | -0.10 ± 0.25 | -0.64 ± 0.24 |
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.
| score on a scale | Placebo | Venglustat 8 mg | Venglustat 15 mg |
|---|---|---|---|
| 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 | 0.02 ± 0.38 | -0.85 ± 0.55 | -0.51 ± 0.38 |
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.
| nanograms per milliliter | Stage 1- Venglustat 8 mg | Stage 1- Venglustat 15 mg |
|---|---|---|
| Day 1: 3 hours Post-Dose | 27.8 ± 11.9 | 50.9 ± 22.5 |
| Month 1: Pre-Dose | 54.7 ± 19.2 | 103.9 ± 50.2 |
| Month 1: 3 hours Post-Dose | 82.1 ± 24.7 | 154.6 ± 61.1 |
| Months 6: Pre-Dose | 57.5 ± 23.5 | 106.2 ± 56.3 |
| Months 18: Pre-Dose | 58.3 ± 22.0 | 120.3 ± 73.1 |
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.
| nanograms per milliliter | Stage 2- Venglustat 15 mg |
|---|---|
| Month 1: Pre-Dose | 109.3 ± 60.7 |
| Month 1: 3 hours Post-Dose | 163.5 ± 79.7 |
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).
| Participants | Stage 1- Placebo | Stage 1- Venglustat 8 mg | Stage 1- Venglustat 15 mg |
|---|---|---|---|
| TEAEs | 62 | 65 | 70 |
| TESAEs | 8 | 15 | 19 |
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).
| Participants | Placebo | Venglustat 8 mg | Venglustat 15 mg |
|---|---|---|---|
| TEAEs | 128 | 65 | 143 |
| TESAEs | 14 | 15 | 26 |
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).
| Participants | Placebo | Venglustat 8 mg | Venglustat 15 mg |
|---|---|---|---|
| Hemoglobin: <=115 g/L (Male); <=95 g/L (Female) | 7 | 3 | 5 |
| Hemoglobin: >=185 g/L (Male); >=165 g/L (Female) | 0 | 0 | 0 |
| Hemoglobin: Decrease from baseline >=20 g/L | 4 | 7 | 5 |
| Hematocrit: <=0.37 v/v (Male); <=0.32 v/v (Female) | 40 | 20 | 42 |
| Hematocrit: >=0.55 v/v (Male); >=0.5 v/v (Female) | 0 | 0 | 0 |
| Erythrocyte (RBC): >=6 * 10^12/L | 1 | 0 | 1 |
| Platelet: <100*10^9/L | 0 | 2 | 1 |
| Platelet: >=700*10^9/L | 0 | 0 | 0 |
| Leukocyte (WBC): <3*10^9/L (Non-Black); <2*10^9/L (Black) | 1 | 2 | 4 |
| Leukocyte (WBC): >=16*10^9/L | 0 | 2 | 1 |
| Neutrophils: <1.5*10^9/L (Non-Black); <1*10^9/L (Black) | 1 | 1 | 3 |
| Lymphocytes: >4*10^9/L | 0 | 1 | 0 |
| Monocytes >0.7*10^9/L | 6 | 3 | 7 |
| Basophils: >0.1*10^9/L | 33 | 5 | 8 |
| Eosinophils: >0.5*10^9/L or >ULN | 7 | 2 | 1 |
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.
| Participants | Placebo | Venglustat 8 mg | Venglustat 15 mg |
|---|---|---|---|
| Glucose: <=3.9 mmol/L and <LLN | 17 | 5 | 12 |
| Glucose: >=11.1 mmol/L (unfasted); >=7 mmol/L (fasted) | 10 | 5 | 19 |
| Albumin: <=25 g/L | 0 | 0 | 0 |
| Sodium: <=129 mmol/L | 1 | 0 | 3 |
| Sodium: >=160 mmol/L | 0 | 0 | 0 |
| Potassium: <3 mmol/L | 0 | 1 | 0 |
| Potassium: >=5.5 mmol/L | 5 | 5 | 11 |
| Chloride: <80 mmol/L | 0 | 1 | 0 |
| Chloride: >115 mmol/L | 1 | 0 | 0 |
| Creatinine: >=150 mcmol/L (Adults) | 50 | 21 | 70 |
| Creatinine: >=30% change from Baseline | 12 | 18 | 25 |
| Creatinine: >=100% change from Baseline | 0 | 1 | 4 |
| Urea Nitrogen: >=17 mmol/L | 1 | 0 | 6 |
| ALT: > 3 ULN | 0 | 0 | 0 |
| AST: >3 ULN | 0 | 0 | 0 |
| Alkaline Phosphatase: >1.5 ULN | 3 | 0 | 0 |
| Total Bilirubin: >1.5 ULN | 2 | 0 | 1 |
| Total Bilirubin: >2 ULN | 0 | 0 | 0 |
| ALT >3 ULN and Bilirubin >2 ULN | 0 | 0 | 0 |
| Direct Bilirubin >35% Bilirubin and Bilirubin >1.5 ULN | 2 | 0 | 0 |
Criteria for potentially clinically significant abnormalities: Urine pH: \<=4.6 and \>=8.
| Participants | Placebo | Venglustat 8 mg | Venglustat 15 mg |
|---|---|---|---|
| Urine pH: <=4.6 | 0 | 0 | 0 |
| Urine pH: >=8 | 0 | 0 | 0 |
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.
| Participants | Placebo | Venglustat 8 mg | Venglustat 15 mg |
|---|---|---|---|
| Sitting Systolic Blood Pressure: <=95 mmHg and decrease from Baseline >=20 mmHg | 0 | 0 | 1 |
| Sitting Systolic Blood Pressure: >=160 mmHg and increase from Baseline >=20 mmHg | 2 | 3 | 10 |
| Sitting Diastolic Blood Pressure: <= 45 mmHg and decrease from Baseline >=10 mmHg | 0 | 0 | 0 |
| Sitting Diastolic Blood Pressure: >=110 mmHg and increase from Baseline >=10 mmHg | 2 | 4 | 7 |
| Sitting Heart Rate: <=50 beats/min and decrease from Baseline >=20 beats/min | 0 | 2 | 2 |
| Sitting Heart Rate: >=120 beats/min and increase from Baseline >=20 beats/min | 0 | 0 | 0 |
| Weight: >=5% decrease from Baseline | 11 | 4 | 13 |
| Weight: >=5% increase from Baseline | 15 | 9 | 15 |
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.
| Participants | Placebo | Venglustat 8 mg | Venglustat 15 mg |
|---|---|---|---|
| Heart Rate: <50 beats/min | 7 | 6 | 13 |
| Heart Rate: <50 beats/min and decrease from Baseline >=20 beats/min | 1 | 0 | 1 |
| Heart Rate: <40 beats/min | 0 | 1 | 1 |
| Heart Rate: <40 beats/min and decrease from Baseline >=20 beats/min | 0 | 0 | 0 |
| Heart Rate: <30 beats/min | 0 | 0 | 0 |
| Heart Rate: >90 beats/min | 4 | 2 | 3 |
| Heart Rate: >90 beats/min and increase from Baseline >=20 beats/min | 2 | 2 | 2 |
| Heart Rate: >100 beats/min | 1 | 0 | 2 |
| Heart Rate: >100 beats/min and increase from Baseline >=20 beats/min | 1 | 0 | 1 |
| Heart Rate: >120 beats/min | 0 | 0 | 0 |
| Heart Rate: >120 beats/min and increase from Baseline >=20 beats/min | 0 | 0 | 0 |
| PR Interval: >200 msec | 8 | 2 | 10 |
| PR Interval: >200 msec and increase from Baseline >=25% | 0 | 0 | 0 |
| PR Interval: >220 msec | 1 | 0 | 2 |
| PR Interval: >240 msec | 0 | 0 | 0 |
| QRS Interval: >110 msec | 11 | 4 | 10 |
| QRS Interval: > 110 msec and increase from Baseline >=25% | 0 | 0 | 1 |
| QRS Interval: >120 msec | 2 | 1 | 3 |
| QRS Interval: >120 msec and increase from Baseline >=25% | 0 | 0 | 1 |
| QT Interval: >500 msec | 0 | 0 | 0 |
| QTc Bazett: >450 msec | 5 | 2 | 3 |
| QTc Bazett: >480 msec | 0 | 0 | 0 |
| QTc Bazett: Increase from Baseline [30-60] msec | 13 | 1 | 5 |
| QTc Bazett: Increase from Baseline >60 msec | 0 | 0 | 0 |
| QTc Fridericia: >450 msec | 4 | 1 | 2 |
| QTc Fridericia: >480 msec | 0 | 0 | 0 |
| QTc Fridericia: Increase from Baseline [30-60] msec | 5 | 1 | 3 |
| QTc Fridericia: Increase from Baseline >60 msec | 0 | 0 | 0 |
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.
| Participants | Placebo | Venglustat 8 mg | Venglustat 15 mg |
|---|---|---|---|
| Baseline: Head | 1 | 1 | 4 |
| Baseline: Heart | 2 | 1 | 1 |
| Baseline: Lung | 0 | 0 | 0 |
| Baseline: Abdomen | 15 | 12 | 24 |
| Baseline: Musculo/Skeletal | 5 | 1 | 4 |
| Baseline: Skin | 7 | 2 | 3 |
| Baseline: Mental Status | 0 | 0 | 0 |
| Month 18: Head | 0 | 0 | 1 |
| Month 18: Heart | 0 | 0 | 1 |
| Month 18: Lung | 0 | 0 | 0 |
| Month 18: Abdomen | 2 | 1 | 0 |
| Month 18: Musculo/Skeletal | 0 | 0 | 1 |
| Month 18: Skin | 1 | 1 | 0 |
| Month 18: Mental Status | 1 | 0 | 0 |
| Month 24: Head | 0 | 0 | 0 |
| Month 24: Heart | 0 | 0 | 0 |
| Month 24: Lung | 0 | 0 | 0 |
| Month 24: Abdomen | 0 | 0 | 0 |
| Month 24: Musculo/Skeletal | 0 | 0 | 0 |
| Month 24: Skin | 0 | 0 | 0 |
| Month 24: Mental Status | 0 | 0 | 0 |
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.
| score on a scale | Placebo | Venglustat 8 mg | Venglustat 15 mg |
|---|---|---|---|
| Baseline | 4.0 ± 4.7 | 3.0 ± 4.1 | 3.4 ± 4.1 |
| Change at Month 3 | -0.1 ± 4.0 | 0.7 ± 4.0 | 0.7 ± 4.3 |
| Change at Month 6 | -0.6 ± 4.2 | 0.9 ± 4.2 | 0.3 ± 3.9 |
| Change at Month 9 | -0.3 ± 4.8 | 0.1 ± 3.7 | 0.7 ± 4.9 |
| Change at Month 12 | -1.9 ± 3.9 | 0.2 ± 4.7 | 1.5 ± 5.3 |
| Change at Month 15 | -1.5 ± 4.4 | -0.1 ± 4.4 | -0.3 ± 4.0 |
| Change at Month 18 | -1.0 ± 4.9 | 0.5 ± 3.0 | 0.0 ± 3.5 |
| Change at Month 21 | 1.0 ± 9.5 | -0.1 ± 1.3 | 1.1 ± 2.8 |
| Change at Month 24 | -0.3 ± 0.5 | 0.8 ± 2.2 | 0.3 ± 1.7 |
| Change at Last on-treatment value | -0.5 ± 5.1 | 0.1 ± 4.0 | 0.3 ± 4.6 |
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.
| Participants | Placebo | Venglustat 8 mg | Venglustat 15 mg |
|---|---|---|---|
| Worsening of LOCS III score >= 0.5 or WHO grade >= 1.0 in nuclear opacification: Any eye | 8 | 3 | 9 |
| Worsening of LOCS III score >= 0.5 or WHO grade >= 1.0 in nuclear opacification: Unilateral | 0 | 0 | 4 |
| Worsening of LOCS III score >= 0.5 or WHO grade >= 1.0 in nuclear opacification: Bilateral | 8 | 3 | 6 |
| Worsening of LOCS III score >= 0.8 or WHO grade >= 1.0 in cortical opacification: Any eye | 4 | 4 | 4 |
| Worsening of LOCS III score >= 0.8 or WHO grade >= 1.0 in cortical opacification: Unilateral | 1 | 0 | 1 |
| Worsening of LOCS III score >= 0.8 or WHO grade >= 1.0 in cortical opacification: Bilateral | 2 | 4 | 3 |
| Worsening of LOCS III score>=0.5 or WHO grade >= 1.0 in posterior subcapsular opacification:Any eye | 2 | 2 | 3 |
| Worsening of LOCS III score>=0.5 or WHO grade >=1.0 in posterior subcapsularopacification:Unilateral | 0 | 1 | 1 |
| Worsening of LOCS III score>=0.5 or WHO grade >=1.0 in posterior subcapsular opacification:Bilateral | 2 | 1 | 2 |
Collected over 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. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Stage 1- Placebo | 0/78 (0%) | 8/78 (10.3%) | 42/78 (53.8%) |
| Stage 1- Venglustat 8 mg | 0/78 (0%) | 15/78 (19.2%) | 46/78 (59%) |
| Stage 1- Venglustat 15 mg | 0/80 (0%) | 19/80 (23.8%) | 48/80 (60%) |
| Stage 2- Placebo | 0/122 (0%) | 6/122 (4.9%) | 32/122 (26.2%) |
| Stage 2- Venglustat 15 mg | 0/119 (0%) | 7/119 (5.9%) | 48/119 (40.3%) |
| Event | Stage 1- Placebo | Stage 1- Venglustat 8 mg | Stage 1- Venglustat 15 mg | Stage 2- Placebo | Stage 2- Venglustat 15 mg |
|---|---|---|---|---|---|
| Renal Cyst InfectionInfections and infestations | 0/78 | 3/78 | 1/80 | 0/122 | 1/119 |
| HaematuriaRenal and urinary disorders | 0/78 | 3/78 | 0/80 | 0/122 | 0/119 |
| Renal Cyst RupturedRenal and urinary disorders | 0/78 | 2/78 | 0/80 | 0/122 | 0/119 |
| AppendicitisInfections and infestations | 1/78 | 1/78 | 2/80 | 0/122 | 0/119 |
| Urinary Tract InfectionInfections and infestations | 1/78 | 0/78 | 2/80 | 0/122 | 0/119 |
| Renal Cyst HaemorrhageRenal and urinary disorders | 0/78 | 0/78 | 0/80 | 0/122 | 2/119 |
| Covid-19Infections and infestations | 0/78 | 0/78 | 0/80 | 2/122 | 0/119 |
| DiverticulitisInfections and infestations | 0/78 | 1/78 | 1/80 | 0/122 | 0/119 |
| Gastroenteritis ViralInfections and infestations | 0/78 | 1/78 | 0/80 | 0/122 | 0/119 |
| InfluenzaInfections and infestations | 0/78 | 1/78 | 0/80 | 0/122 | 0/119 |
| Event | Stage 1- Placebo | Stage 1- Venglustat 8 mg | Stage 1- Venglustat 15 mg | Stage 2- Placebo | Stage 2- Venglustat 15 mg |
|---|---|---|---|---|---|
| HeadacheNervous system disorders | 6/78 | 8/78 | 11/80 | 7/122 | 8/119 |
| NasopharyngitisInfections and infestations | 10/78 | 5/78 | 6/80 | 2/122 | 0/119 |
| FatigueGeneral disorders | 1/78 | 4/78 | 9/80 | 3/122 | 2/119 |
| Back PainMusculoskeletal and connective tissue disorders | 8/78 | 6/78 | 8/80 | 5/122 | 2/119 |
| CoughRespiratory, thoracic and mediastinal disorders | 1/78 | 5/78 | 8/80 | 1/122 | 7/119 |
| Urinary Tract InfectionInfections and infestations | 6/78 | 5/78 | 7/80 | 3/122 | 1/119 |
| HypertensionVascular disorders | 2/78 | 5/78 | 7/80 | 4/122 | 4/119 |
| NauseaGastrointestinal disorders | 1/78 | 6/78 | 7/80 | 0/122 | 6/119 |
| Covid-19Infections and infestations | 5/78 | 6/78 | 1/80 | 3/122 | 7/119 |
| Upper Respiratory Tract InfectionInfections and infestations | 0/78 | 4/78 | 6/80 | 4/122 | 6/119 |
Analysis was performed on all participants randomized in the study.
| Age, Continuous(years) | Stage 1- Placebo | Stage 1- Venglustat 8 mg | Stage 1- Venglustat 15 mg | Stage 2- Placebo | Stage 2- Venglustat 15 mg | Total Title |
|---|---|---|---|---|---|---|
| Mean | 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(Participants) | Stage 1- Placebo | Stage 1- Venglustat 8 mg | Stage 1- Venglustat 15 mg | Stage 2- Placebo | Stage 2- Venglustat 15 mg | Total Title |
|---|---|---|---|---|---|---|
| Female | 37 | 31 | 34 | 46 | 48 | 196 |
| Male | 41 | 47 | 46 | 77 | 71 | 282 |
| Race (NIH/OMB)(Participants) | Stage 1- Placebo | Stage 1- Venglustat 8 mg | Stage 1- Venglustat 15 mg | Stage 2- Placebo | Stage 2- Venglustat 15 mg | Total Title |
|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 1 | 0 | 1 |
| Asian | 27 | 27 | 27 | 52 | 55 | 188 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 1 | 0 | 0 | 1 |
| Black or African American | 0 | 1 | 0 | 2 | 0 | 3 |
| White | 48 | 50 | 52 | 66 | 64 | 280 |
| More than one race | 1 | 0 | 0 | 0 | 0 | 1 |
| Unknown or Not Reported | 2 | 0 | 0 | 2 | 0 | 4 |
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Plan to share: Yes — Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
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