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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT03523728
Registration number
NCT03523728
Ethics application status
Date submitted
1/05/2018
Date registered
14/05/2018
Date last updated
3/02/2023
Titles & IDs
Public title
A Medical Research Study Designed to Determine if Venglustat Can be a Future Treatment for ADPKD Patients
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Scientific title
Multicenter, Randomized, Double-blind, Placebo-controlled Two Stage Study to Characterize the Efficacy, Safety, Tolerability and Pharmacokinetics of GZ/SAR402671 in Patients at Risk of Rapidly Progressive Autosomal Dominant Polycystic Kidney Disease (ADPKD)
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Secondary ID [1]
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2017-004084-12
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Secondary ID [2]
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EFC15392
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Universal Trial Number (UTN)
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Trial acronym
STAGED-PKD
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Polycystic Kidney, Autosomal Dominant
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Condition category
Condition code
Renal and Urogenital
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Other renal and urogenital disorders
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Human Genetics and Inherited Disorders
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Other human genetics and inherited disorders
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Venglustat
Treatment: Drugs - Placebo
Placebo Comparator: Stage 1- Placebo - Participants from Stage 1 were randomized to receive 2 capsules of placebo matched to venglustat once daily for treatment period of 24 months.
Experimental: Stage 1- Venglustat 8 mg - 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.
Experimental: Stage 1- Venglustat 15 mg - 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.
Placebo Comparator: Stage 2- Placebo - Participants from Stage 2 were randomized to receive 1 capsule of placebo matched to venglustat once daily for treatment period of 24 months.
Experimental: Stage 2- Venglustat 15 mg - Participants from Stage 2 were randomized to receive 1 capsule of venglustat 15 mg once daily for treatment period of 24 months.
Treatment: Drugs: Venglustat
Pharmaceutical form: capsule; Route of administration: oral
Treatment: Drugs: Placebo
Pharmaceutical form: capsule; Route of administration: oral
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Annualized Slope of Change in Total Kidney Volume (TKV) From Baseline to Month 18: Stage 1
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Assessment method [1]
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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.
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Timepoint [1]
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From Baseline to Month 18
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Primary outcome [2]
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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
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Assessment method [2]
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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.
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Timepoint [2]
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From Baseline to Month 24
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Secondary outcome [1]
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Annualized Rate of Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Month 24: Stage 1
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Assessment method [1]
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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.
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Timepoint [1]
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From Baseline to Month 24
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Secondary outcome [2]
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Annualized Slope of Change in Total Kidney Volume (TKV) From Baseline to Month 18: Combined Stage 1 and Stage 2
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Assessment method [2]
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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.
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Timepoint [2]
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From Baseline to Month 18
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Secondary outcome [3]
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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
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Assessment method [3]
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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.
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Timepoint [3]
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From Baseline to Month 18
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Secondary outcome [4]
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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
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Assessment method [4]
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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.
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Timepoint [4]
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From Baseline to Month 24
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Secondary outcome [5]
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Change in Fatigue Severity as Measured by Brief Fatigue Inventory (BFI-SF)-Item 3 Scale Score From Baseline to Month 18: Stage 1
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Assessment method [5]
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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.
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Timepoint [5]
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From Baseline to Month 18
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Secondary outcome [6]
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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
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Assessment method [6]
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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.
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Timepoint [6]
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From Baseline to Month 24
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Secondary outcome [7]
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Pharmacokinetics: Plasma Concentration of Venglustat: Stage 1
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Assessment method [7]
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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.
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Timepoint [7]
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Day 1: 3 hours Post-Dose, Month 1: Pre-Dose and 3 hours Post-Dose, Month 6: Pre-Dose, Month 18: Pre-Dose
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Secondary outcome [8]
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Pharmacokinetics: Plasma Concentration of Venglustat: Stage 2
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Assessment method [8]
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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.
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Timepoint [8]
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Month 1: Pre-dose and 3 hours Post-dose
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Secondary outcome [9]
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Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs): Stage 1
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Assessment method [9]
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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).
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Timepoint [9]
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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
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Secondary outcome [10]
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Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs): Combined Stage 1 and Stage 2
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Assessment method [10]
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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).
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Timepoint [10]
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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
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Secondary outcome [11]
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Number of Participants With Potentially Clinically Significant Abnormalities: Hematology: Combined Stage 1 and Stage 2
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Assessment method [11]
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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).
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Timepoint [11]
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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
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Secondary outcome [12]
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Number of Participants With Potentially Clinically Significant Abnormalities: Clinical Chemistry: Combined Stage 1 and Stage 2
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Assessment method [12]
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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.
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Timepoint [12]
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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
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Secondary outcome [13]
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Number of Participants With Potentially and Clinically Significant Abnormalities: Urinalysis: Combined Stage 1 and Stage 2
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Assessment method [13]
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Criteria for potentially clinically significant abnormalities: Urine pH: <=4.6 and >=8.
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Timepoint [13]
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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
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Secondary outcome [14]
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Number of Participants With Potentially and Clinically Significant Abnormalities: Vital Signs: Combined Stage 1 and Stage 2
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Assessment method [14]
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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.
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Timepoint [14]
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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
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Secondary outcome [15]
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Number of Participants With Potentially Clinically Significant Abnormalities: Electrocardiogram: Combined Stage 1 and Stage 2
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Assessment method [15]
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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.
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Timepoint [15]
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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
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Secondary outcome [16]
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Number of Participants With Physical Examination Abnormalities: Combined Stage 1 and Stage 2
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Assessment method [16]
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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.
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Timepoint [16]
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Baseline, Month 18, Month 24
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Secondary outcome [17]
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Change From Baseline in Beck Depression Inventory-II (BDI-II) Score: Combined Stage 1 and Stage 2
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Assessment method [17]
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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.
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Timepoint [17]
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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)
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Secondary outcome [18]
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Number of Participants With Worsening Lens Opacity From Baseline During the Treatment-emergent Period: Combined Stage 1 and Stage 2
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Assessment method [18]
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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.
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Timepoint [18]
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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
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Eligibility
Key inclusion criteria
Inclusion criteria:
- Male or female adult with ADPKD with age at the time the consent was signed:
1. between 18 to 50 years (both inclusive) for participants from Stage 1.
2. between 18 to 50 years (both inclusive) for participants from Stage 2 with eGFR
between 45 and 89.9 milliliters per minute per 1.73 meter square (mL/min/1.73
m^2) during screening period.*
3. between 18 to 55 years (both inclusive) for participants from Stage 2 with eGFR
between 30 and 44.9 mL/min/1.73 m^2 during screening period.*
- Diagnosis of ADPKD in participants with a family history would be based on unified Pei
criteria. In the absence of a family history, the diagnosis would be based on the
presence of renal cysts bilaterally, totaling at least 20, in the absence of findings
suggestive of other cystic renal diseases.
- 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 45 to 89.9 mL/min/1.73 m^2 during
screening period* (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]
equation) for Stage 1.
- 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.
- Stable treatment regimen of antihypertensive therapy for at least 30 days prior to the
screening visit for hypertensive participant.
- Able to read, comprehend, and respond to the study questionnaires.
- Participant had given voluntary written informed consent before performance of any
study related procedures not part of standard medical care.
- Participant had no access to tolvaptan at the time of study start or tolvaptan was not
indicated for treatment of participant according to treating physician (participant
does not meet recommended criteria for treatment, refuses to initiate or does not
tolerate treatment with tolvaptan).
- The participants, if female of childbearing potential, must have had a negative blood
pregnancy test (ß-human chorionic gonadotropin [ß-hCG]) at the screening visit and a
negative urine pregnancy test at the baseline visit.
- Female participants of childbearing potential and male participants must have had
agreed to practice true abstinence in line with their preferred and usual lifestyle or
to use double-contraceptive methods (including a highly effective method of
contraception for female participants of childbearing potential) for the entire
duration of the study and for at least 6 weeks for females and 90 days for males
following their last dose of study drug.
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Minimum age
18
Years
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Maximum age
55
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
Exclusion criteria:
- Systolic blood pressure greater than (>) 160 millimeters of Mercury (mmHg) at Run-in
and Baseline visits.
- Administration within 3 months prior to the screening visit of tolvaptan or other
Polycystic Kidney Disease-modifying agents (somatostatin analogues).
- Participation in another investigational interventional study or use of IMP, within 3
months or 5 half lives, whichever was longer, before randomization.
- The participant had a positive result of any of the following tests: hepatitis B
surface antigen (HBsAg), anti-hepatitis C virus (anti HCV) antibodies, anti-human
immunodeficiency virus 1 and 2 antibodies (anti HIV1 and anti HIV2 Ab). Participants
with a positive hepatitis B surface antibody (HBsAb) test were eligible if other
criteria were met (i.e., negative tests for: HBsAg, hepatitis B core antibody
[HBcAb]). Participants immune due to natural infection (positive hepatitis B surface
antibody (HBsAb), negative hepatitis B surface antigen (HBsAg) and positive hepatitis
B core antibody [HBcAb]) were eligible if they had negative hepatitis B vaccine (HBV)
deoxyribonucleic acid (DNA) test.
- A history of drug and/or alcohol abuse within the past year prior to the screening
visit. A history of alcohol dependence within the 5 years prior to the screening
visit.
- The participant was scheduled for in-patient hospitalization including elective
surgery, during the study.
- The participant had a clinically significant, uncontrolled medical condition that, in
the opinion of the investigator, would put the safety of the participant at risk
through participation, or which would affect the efficacy or safety analysis if the
condition exacerbated during the study, or that might significantly interfere with
study compliance, including all prescribed evaluations and follow-up activities.
- The participants, in the opinion of the investigator, was unable to adhere to the
requirements of the study or unable to undergo study assessments (e.g., had
contraindications to pupillary dilation or unable to undergo magnetic resonance
imaging (MRI) [For example: participant's weight exceeds weight capacity of the MRI,
ferromagnetic metal prostheses, aneurysm clips, severe claustrophobia, large
abdominal/back tattoos, etc.]).
- Any country-related specific regulation that would prevent the participant from
entering the study.
- The participants did not adhere to treatment (less than [<] 70 percent [%] compliance
rate) in the run-in.
- The participant had, according to World Health Organization (WHO) Grading, a cortical
cataract greater than or equal to (>=)one-quarter of the lens circumference (Grade
cortical cataract-2 [COR-2]) or a posterior subcapsular cataract >=2 millimeter (Grade
posterior subcapsular cataract-2 [PSC-2]). Participant with nuclear cataracts would
not be excluded.
- The participant was then receiving potentially cataractogenic medications, including a
chronic regimen (more frequently than every 2 weeks) of any route of corticosteroids
(including medium and high potency topical steroids) or any medication that might
cause cataract, according to the Prescribing Information.
- The participant had received strong or moderate inducers or inhibitors of CYP3A4
within 14 days or 5 half-lives, whichever was longer, prior to randomization. This
also included the consumption of grapefruit, grapefruit juice, or grapefruit
containing products within 72 hours of starting venglustat administration.
- The participant was pregnant, or lactating.
- Liver enzymes (alanine aminotransferase /aspartate aminotransferase ) or total
bilirubin >2 times the upper limit of normal unless the participant had the diagnosis
of Gilbert syndrome. Participants with the Gilbert syndrome should have had no
additional symptoms or signs which suggested hepatobiliary disease and serum total
bilirubin level no more than 3 milligrams per deciliter (mg/dL) (51 [micromoles per
Liter] mcmol/L) with conjugated bilirubin less than 20% of the total bilirubin
fraction.
- Presence of severe depression as measured by Beck Depression Inventory-II (BDI-II) >28
and/or a history of a major affective disorder within 1 year of the screening visit.
- Known hypersensitivity to venglustat or any component of the excipients.
The above information was not intended to contain all considerations relevant to a
participant's potential participation in a clinical trial.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people assessing the outcomes
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2/Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Terminated
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
4/10/2018
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
3/08/2021
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Sample size
Target
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Accrual to date
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Final
478
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Recruitment in Australia
Recruitment state(s)
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Recruitment hospital [1]
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Investigational Site Number 0360002 - Herston
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Recruitment hospital [2]
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Investigational Site Number 0360003 - Nedlands
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Investigational Site Number 0360001 - Westmead
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Recruitment postcode(s) [1]
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4029 - Herston
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Recruitment postcode(s) [2]
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6009 - Nedlands
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Recruitment postcode(s) [3]
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2145 - Westmead
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Recruitment outside Australia
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Santa Fe
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Austria
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Graz
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Bruxelles
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Leuven
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Edmonton
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Canada
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Canada
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Beijing
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China
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China
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China
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China
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China
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China
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China
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Praha 2
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Denmark
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Roskilde
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France
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France
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Germany
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Essen
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Germany
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Germany
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Germany
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Mainz
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Israel
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Ashdod
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Israel
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Italy
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Milano
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Italy
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Napoli
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Japan
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Korea, Republic of
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Seoul
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Amsterdam
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Groningen
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Portugal
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Almada
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Portugal
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Portugal
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Loures
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Bucuresti
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Romania
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Romania
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Timisoara
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Spain
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Barcelona
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Spain
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Madrid
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Taichung
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Taipei
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Turkey
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Istanbul
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Turkey
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Kayseri
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Turkey
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Kocaeli
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United Kingdom
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State/province [86]
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Sheffield
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Genzyme, a Sanofi Company
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
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:
- To determine the effect of venglustat on the rate of renal function decline (Stage 1)
and on the rate of TKV growth (Stage 2).
- To evaluate the pharmacokinetics (PK) of venglustat in ADPKD participants (Stages 1 and
2).
- To determine the effect of venglustat on pain and fatigue, based on participant reported
diary (Stages 1 and 2).
- Safety/tolerability objectives:
- To characterize the safety profile of venglustat (Stages 1 and 2).
- To evaluate the effect of venglustat on mood using Beck Depression Inventory II (BDI-II)
(Stages 1 and 2).
- To evaluate the effect of venglustat on the lens by ophthalmological examination (Stages
1 and 2).
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Trial website
https://clinicaltrials.gov/ct2/show/NCT03523728
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Clinical Sciences & Operations
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Address
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Sanofi
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Country
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Phone
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Fax
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Email
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Contact person for public queries
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT03523728
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