ADPKD kidney disease
Conditions
Interventions
In Stage 1, during the run-in period the patient will receive placebo matching
GZ/SAR402671 (2 capsules) once daily for 2 weeks.
During the double-blind core treatment period, the patient will receiv
Sponsors
Sanofi-aventis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Male or female adult with ADPKD: a) between ages of 18 and 50 years (inclusive) for patients in Stage 1 b) between 18 and 50 years (inclusive) for patients in Stage 2 with an eGFR between 45 and 89.9 mL/min/1.73 m2 during the screening period c) between 18 and 55 years (inclusive) for patients in Stage 2 with an eGFR between 30 and 44.9 mL/min/1.73 m2 during the screening period Diagnosis of ADPKD in patients with a family history, will be based on unified Pei criteria. In the absence of a family history, the diagnosis will 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. - Estimated glomerular filtration rate between 45 to 89,9 mL/min/1.73 m2 during the screening period (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) for stage 1. - Estimated glomerular filtration rate between 30 and 89.9 mL/min/1.73 m2 during the screening period (CKD-EPI equation) for Stage 2. - Stable treatment regimen of antihypertensive therapy for at least 30 days prior to the screening visit for hypertensive patient. - 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 or does not tolerate treatment with tolvaptan). - The patient, if female of childbearing potential, must have a negative blood pregnancy test (*-human chorionic gonadotropin [*-hCG]) at the screening visit and a negative urine pregnancy test at the baseline visit. - Female patients of childbearing potential and male patients must agree 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
Exclusion criteria
Exclusion criteria: - Systolic BP >160 mmHg at run-in and baseline visits. - History of administration of tolvaptan or other Polycystic Kidney Disease-modifying agents (somatostatin analogues) within 3 months prior to the screening visit. - 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, etc]). - Current participation in another investigational interventional study or use of investigational medicinal product (IMP), within 3 months or 5 half-lives, whichever is longer, before randomization. - The patient has 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). Patients with a positive hepatitis B surface antibody (HBsAb) test are eligible if other criteria are met (ie, negative tests for: HBsAg, hepatitis B core antibody [HBcAb], and hepatitis C virus antibody [HCVAb]). Patients immune due to natural infection (positive HBsAb, negative HBsAg, positive HBcAb) are eligible if they have a negative HBV 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. - Any patient who is the Investigator or any Subinvestigator, research assistant, pharmacist, study coordinator, other staff, or relative thereof directly involved in the conduct of the study. - The patient is scheduled for in-patient hospitalization including elective surgery, during the study. - The patient has a clinically significant, uncontrolled medical condition that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the condition exacerbated during the study, or that may significantly interfere with study compliance, including all prescribed evaluations and follow-up activities. The list of medical conditions that should be taken into account includes, but is not limited to the following: Congestive heart failure New York Heart Association (NYHA) Grade III/IV), clinically significant cardiac arrhythmia, severe unstable angina pectoris within 6 months of Visit 1, hypertensive emergency within 6 months of Visit 1, stroke or transient ischemic attack within 3 months of Visit 1, myocardial infarction within 3 months of Visit 1, current malignancy, tuberculosis (current or untreated), Cushing's disease, Addison's disease, uncontrolled diabetes mellitus, uncontrolled thyroid disorder - Any country-related specific regulation that would prevent the patient from entering the study. - The patients did not adhere to treatment (<70% compliance rate) in the run-in. - The patient has, according to World Health Organization (WHO) Grading (13), a cortical cataract *1-quarter of the lens circumference (Grade cortical cataract-2 [COR-2]) or a posterior subcapsular cataract
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Stage 1 Primary endpoint: *Annualized rate of change in TKV based on MRI from baseline to 18 months. Stage 2 Primary endpoint: *Annualized rate of change in eGFR (CKD-EPI equation) from baseline to 24 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| Stage 1 Secondary endpoints: * Annualized rate of change in eGFR (CKD-EPI equation) from baseline to 18 months. * Change in Pain (BPI - Item 3) from baseline to 18 months, from the daily symptom diary. * Change in fatigue (BFI - Item 3) from baseline to 18 months, from the daily symptom diary. * Plasma venglustat concentrations. Exporatory endpoint: * Annualized rate of change in total liver volume based on MRI (in patients with htTLV >2 L/m) from baseline to 18 months Stage 2 Secondary endpoints: * Annualized rate of change in TKV based on MRI from baseline to 18 months. * Change in pain (BPI - Item 3) from baseline to 24 months, from the daily symptom diary. * Change in fatigue (BFI - Item 3) from baseline to 24 months, from the daily symptom diary. * Plasma venglustat concentrations. Exploratory endpoints: * Annualized rate of change in mGFR from baseline to 24 months (substudy). * Annualized rate of change in eGFR (CKD-EPI equation) from baseline to 24 months in patients with a screening eGFR between 30 and 44.9 mL/min/1.73 m2. * Annualized rate of change in total liver volume based on MRI (in patients with htTLV >2 L/m) from baseline to 18 months Stage 1 and Stage 2: 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 during the treatment-emergent period. * Change in the lens clarity by ophthalmological examination during the treatment-emergent period. | — |
Countries
Netherlands
Outcome results
None listed