Clinical Trials List
Protocol NumberEFC15392
NCT Number(ClinicalTrials.gov Identfier)NCT03523728
2018-10-01 - 2022-02-28
Phase II
Recruiting2
ICD-10Q61.2
Polycystic kidney, adult type
ICD-9753.13
Polycystic kidney, autosomal dominant
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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Trial Applicant
-
Sponsor
Sanofi
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 王怡寬 Division of Nephrology
- Ya-Fei Yang Division of Nephrology
- 周哲毅 Division of Nephrology
- 蔡宜佑 Division of Nephrology
- 郭慧亮 Division of Nephrology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 高芷華 Division of General Internal Medicine
- 林裕峯 Division of General Internal Medicine
- VIN-CENT Wu Division of General Internal Medicine
- 黃道民 Division of General Internal Medicine
- 林裕峰 Division of General Internal Medicine
- 葉伯廷 Division of General Internal Medicine
- 陳怡婷 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Rapidly Progressive Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Objectives
Stage 1
Primary objective:
! To determine the effect of GZ/SAR402671 on the rate of total
kidney volume (TKV) growth in patients at risk of rapidly
progressive ADPKD.
Secondary objectives:
! To determine the effect of GZ/SAR402671 on the rate of renal
function (estimated glomerular filtration rate [eGFR]) decline.
! To evaluate the pharmacokinetics (PK) of GZ/SAR402671 in
ADPKD patients.
! Safety/tolerability objectives:
- To characterize the safety profile of GZ/SAR402671.
- To evaluate the effect of GZ/SAR402671 on mood using
Beck Depression Inventory-II (BDI-II).
- To evaluate the effect of GZ/SAR402671 on the lens by
ophthalmological examination.
- To evaluate change in nocturia from baseline to 18 months
based on patient reported diary
Stage 2
Primary objective:
! To determine the effect of GZ/SAR402671 on rate of renal
function (eGFR) decline as compared to placebo in patients at
risk of rapidly progressive ADPKD.
Secondary objectives:
! To determine the effect of GZ/SAR402671 on the rate of
TKV growth.
! To evaluate the effect of GZ/SAR402671 on kidney concentrating
ability by assessing urine osmolality (in patients not on diuretic).
! To evaluate the PK of GZ/SAR402671 in ADPKD patients.
! Safety/tolerability objectives:
- To characterize the safety profile of GZ/SAR402671.
- To evaluate the effect of GZ/SAR402671 on mood using
BDI-II.
- To evaluate the effect of GZ/SAR402671 on the lens by
ophthalmological examination.
- To evaluate change in nocturia from baseline to 24 months
based on patient reported diary.
Test Drug
venglustat
Active Ingredient
venglustat
Dosage Form
capsule
Dosage
4mg/15mg
Endpoints
Stage 1
Primary endpoint:
! Annualized rate of change in TKV based on MRI from baseline to
18 months.
Secondary endpoints:
! Annualized rate of change in eGFR (CKD-EPI equation) from
baseline to 18 months.
! Plasma GZ/SAR402671 concentrations.
! Safety/tolerability endpoints:
- Safety in terms of TEAEs/AEs/SAEs, laboratory parameters,
vital signs, electrocardiogram and findings from physical
examination will be assessed through the study and will be
reported in the eCRF. Adverse event data will be collected
throughout the study. Treatment-emergent AEs are defined
as AEs that develop, worsen (according to the Investigator
opinion), or become serious during the treatment period.
The treatment period is defined as the time from first dose
of study treatment up to 30 days after last dose of study
treatment
- Change in score of BDI-II from baseline to 18 months.
- Change in the lens clarity by ophthalmological examination
from baseline to 18 months.
- Change in nocturia from baseline to 18 months based on
patient reported diary
Stage 2
Primary endpoint:
! Annualized rate of change in eGFR (CKD-EPI equation) from
baseline to 24 months.
Secondary endpoints:
! Annualized rate of change in TKV based on MRI from baseline to
18 months.
! Change in urine osmolality from baseline to 24 months
(in patients not on diuretic).
! Plasma GZ/SAR402671 concentrations.
! Safety/tolerability endpoints:
- Safety in terms of TEAEs/AEs/SAEs, laboratory parameters,
vital signs, electrocardiogram and findings from physical
examination will be assessed through the study and will be
reported in the eCRF. Adverse event data will be collected
throughout the study. Treatment-emergent AEs are defined
as AEs that develop, worsen (according to the Investigator
opinion), or become serious during the treatment period.
The treatment period is defined as the time from first dose
of study treatment up to 30 days after last dose of study
treatment.
- Change in score of BDI-II from baseline to 24 months.
- Change in the lens clarity by ophthalmological examination
from baseline to 24 months.
- Change in nocturia from baseline to 24 months based on
patient reported diary
Primary endpoint:
! Annualized rate of change in TKV based on MRI from baseline to
18 months.
Secondary endpoints:
! Annualized rate of change in eGFR (CKD-EPI equation) from
baseline to 18 months.
! Plasma GZ/SAR402671 concentrations.
! Safety/tolerability endpoints:
- Safety in terms of TEAEs/AEs/SAEs, laboratory parameters,
vital signs, electrocardiogram and findings from physical
examination will be assessed through the study and will be
reported in the eCRF. Adverse event data will be collected
throughout the study. Treatment-emergent AEs are defined
as AEs that develop, worsen (according to the Investigator
opinion), or become serious during the treatment period.
The treatment period is defined as the time from first dose
of study treatment up to 30 days after last dose of study
treatment
- Change in score of BDI-II from baseline to 18 months.
- Change in the lens clarity by ophthalmological examination
from baseline to 18 months.
- Change in nocturia from baseline to 18 months based on
patient reported diary
Stage 2
Primary endpoint:
! Annualized rate of change in eGFR (CKD-EPI equation) from
baseline to 24 months.
Secondary endpoints:
! Annualized rate of change in TKV based on MRI from baseline to
18 months.
! Change in urine osmolality from baseline to 24 months
(in patients not on diuretic).
! Plasma GZ/SAR402671 concentrations.
! Safety/tolerability endpoints:
- Safety in terms of TEAEs/AEs/SAEs, laboratory parameters,
vital signs, electrocardiogram and findings from physical
examination will be assessed through the study and will be
reported in the eCRF. Adverse event data will be collected
throughout the study. Treatment-emergent AEs are defined
as AEs that develop, worsen (according to the Investigator
opinion), or become serious during the treatment period.
The treatment period is defined as the time from first dose
of study treatment up to 30 days after last dose of study
treatment.
- Change in score of BDI-II from baseline to 24 months.
- Change in the lens clarity by ophthalmological examination
from baseline to 24 months.
- Change in nocturia from baseline to 24 months based on
patient reported diary
Inclution Criteria
Inclusion criteria:
! Male or female adult with ADPKD diagnosed by unified Pei
criteria between the ages of 18 to 50 years (both inclusive) at
screening.
! Mayo Imaging Classification of ADPKD Class 1C, 1D, or 1E.
! Estimated glomerular filtration rate between
45 to 90 mL/min/1.73 m2 at screening (Chronic Kidney Disease
Epidemiology Collaboration [CKD-EPI]).
! Stable treatment regimen of antihypertensive therapy for at least
30 days prior to the screening visit for hypertensive patients.
! Able to read, comprehend and respond to the study
questionnaires.
! Patient has given voluntary written informed consent before
performance of any study related procedures not part of standard
medical care.
! Patient does not have access to tolvaptan at the time of study
start or tolvaptan is not indicated for treatment of patient
according to treating physician (patient does not meet
recommended criteria for treatment, refuses to initiate or does
not tolerate treatment with tolvaptan).
! Male or female adult with ADPKD diagnosed by unified Pei
criteria between the ages of 18 to 50 years (both inclusive) at
screening.
! Mayo Imaging Classification of ADPKD Class 1C, 1D, or 1E.
! Estimated glomerular filtration rate between
45 to 90 mL/min/1.73 m2 at screening (Chronic Kidney Disease
Epidemiology Collaboration [CKD-EPI]).
! Stable treatment regimen of antihypertensive therapy for at least
30 days prior to the screening visit for hypertensive patients.
! Able to read, comprehend and respond to the study
questionnaires.
! Patient has given voluntary written informed consent before
performance of any study related procedures not part of standard
medical care.
! Patient does not have access to tolvaptan at the time of study
start or tolvaptan is not indicated for treatment of patient
according to treating physician (patient does not meet
recommended criteria for treatment, refuses to initiate or does
not tolerate treatment with tolvaptan).
Exclusion Criteria
Exclusion criteria:
! Systolic BP >160 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).
! The patient, in the opinion of the Investigator, is unable to adhere
to the requirements of the study or unable to undergo study
assessments (eg, has contraindications to pupillary dilation or
unable to undergo magnetic resonance imaging [MRI]) [For
example: patient’s weight exceeds weight capacity of the MRI,
ferromagnetic metal prostheses, aneurysm clips, severe
claustrophobia, large abdominal/back tattoos]).
! The patient has, according to World Health Organization (WHO)
Grading, a cortical cataract >1-quarter of the lens circumference
(Grade cortical cataract-2 [COR-2]) or a posterior subcapsular
cataract >2 mm (Grade posterior subcapsular cataract-2
[PSC-2]). Patients with nuclear cataracts will not be excluded.
! The patient is currently 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 may
cause cataract, according to the Prescribing Information.
! The patient has received strong or moderate inducers or
inhibitors of CYP3A4 within 14 days or 5 half-lives, whichever is
longer, prior to randomization. This also includes the
consumption of grapefruit, grapefruit juice, or grapefruit
containing products within 72 hours of starting GZ/SAR402671
administration.
! Systolic BP >160 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).
! The patient, in the opinion of the Investigator, is unable to adhere
to the requirements of the study or unable to undergo study
assessments (eg, has contraindications to pupillary dilation or
unable to undergo magnetic resonance imaging [MRI]) [For
example: patient’s weight exceeds weight capacity of the MRI,
ferromagnetic metal prostheses, aneurysm clips, severe
claustrophobia, large abdominal/back tattoos]).
! The patient has, according to World Health Organization (WHO)
Grading, a cortical cataract >1-quarter of the lens circumference
(Grade cortical cataract-2 [COR-2]) or a posterior subcapsular
cataract >2 mm (Grade posterior subcapsular cataract-2
[PSC-2]). Patients with nuclear cataracts will not be excluded.
! The patient is currently 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 may
cause cataract, according to the Prescribing Information.
! The patient has received strong or moderate inducers or
inhibitors of CYP3A4 within 14 days or 5 half-lives, whichever is
longer, prior to randomization. This also includes the
consumption of grapefruit, grapefruit juice, or grapefruit
containing products within 72 hours of starting GZ/SAR402671
administration.
The Estimated Number of Participants
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Taiwan
16 participants
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Global
560 participants
