ong-term treatment of autosomal dominant polycystic kidney disease (ADPKD) with venglustat

Phase 1

Conditions: Congenital cystic kidney disease
MedDRA version: 20.0Level: PTClassification code 10010428Term: Congenital cystic kidney diseaseSystem Organ Class: 10010331 - Congenital, familial and genetic disorders
Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Registration Number: EUCTR2020-004400-34-BE

Lead Sponsor: Sanofi-Aventis Recherche & Développement

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 640

Inclusion Criteria

- Male or female adult with ADPKD who has completed the treatment period in Stage 1 or Stage 2 of Study EFC15392.

- The patient has an eGFR >30 mL/min/1.73 m2:
a) measured at Visit 11 of the EFC15392 study for participant enrolled in the LTS15823 study at the time of Visit 12 (Month 24; end-of treatment visit) of the EFC15392 study.
b) measured at Screening visit for participant enrolled in the LTS15823 study not concomitantly to the Visit 12 (Month 24; end-of treatment visit) of the EFC15392 study.

- Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
a) Male participants must agree to practice true abstinence in line with their preferred and usual lifestyle or to use double-contraceptive methods for the entire duration of the study and for at least 90 days following their last dose of IMP.
b) Female participants must have a negative urine pregnancy test at the Baseline visit and 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 the entire duration of the study and for at least 6 weeks following their last dose of IMP.

- Capable of giving signed informed consent before performance of any study related procedures not part of standard medical care.

- Able to read, comprehend, and respond to the study questionnaires.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 640
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:

For participants who have lag phase between the end of the EFC15392 study and Screening visit (Visit 0) in the LTS15823 study:
-The patient has a new clinically significant, uncontrolled medical condition that, in the opinion of the Investigator, would put the safety of the patient 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.
-A history of drug abuse and/or alcohol abuse or alcohol dependence during the lag phase between the end of the EFC15392 study and Screening visit (Visit 0) in the LTS15823 study when applicable.
-Administration of tolvaptan or other polycystic kidney disease-modifying agents (somatostatin analogues) within 3 months prior to the Screening visit (Visit 0) in the LTS15823 study when applicable.
-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 the Baseline visit (including consumption of grapefruit-containing products within 72 hours of starting venglustat administration).
-Participation in another investigational interventional study or use of IMP, within 3 months or 5 half-lives, whichever is longer, before the Baseline visit (Visit 1) except participation in
the EFC15392 study when applicable.
-Liver enzymes (alanine aminotransferase /aspartate aminotransferase) or total bilirubin >2 times the upper limit of normal unless the patient has the diagnosis of Gilbert syndrome. Patients with the Gilbert syndrome should have no additional symptoms or signs which suggest hepatobiliary disease and serum total bilirubin level no more than 3 mg/dL (51 µmol/L) with conjugated bilirubin less than 20% of the total bilirubin fraction.

For participants with or without lag phase between the end of EFC15392 study and entry into LTS15823 study:
-The patient is pregnant or lactating.
-Presence of severe depression as measured by Beck Depression Inventory II >28 at Visit 1 (for participants enrolled in the LTS15823 study at the time of the end of treatment visit of the EFC15392 study) or at Visit 0 (for participants enrolled in the LTS15823 study after the end-of-treatment visit of the EFC15392 study).
-Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the effect of early versus delayed treatment with venglustat on the total kidney volume (TKV) in participants at risk of rapidly progressive ADPKD.;Secondary Objective: - To determine the effect of early versus delayed treatment with venglustat on the renal function (estimated glomerular filtration rate [eGFR]).<br><br>- To characterize the safety profile of venglustat.<br><br>- To evaluate the effect of venglustat on the lens by ophthalmological examination.<br><br>- To evaluate the effect of venglustat on mood using Beck Depression Inventory-II (BDI-II).;Primary end point(s): Percent change in TKV: Percent change in TKV based on magnetic resonance imaging (MRI) from the EFC15392 study baseline to 24 months of open-label extension study, in early treated and delayed-treated participants;Timepoint(s) of evaluation of this end point: From the EFC15392 study baseline to 24 months of open-label extension study

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1 - Change in eGFR: Change in eGFR (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) from the EFC15392 study baseline to 24 months of open label extension study, in early treated and delayed-treated participants<br><br>2 - Number of adverse events<br><br>3 - Change in lens clarity: Change from EFC15392 study baseline in the lens clarity by ophthalmological examination during the open label extension treatment-emergent period<br><br>4 - Change in score of Beck Depression Inventory- II (BDI-II): Change from EFC15392 study baseline in BDI II score during the open-label extension treatment emergent period;Timepoint(s) of evaluation of this end point: 1: From the EFC15392 study baseline to 24 months of open-label extension study<br><br>2: From 1st treatment intake to last treatment of open-label extension study + 30 days<br><br>3,4: From EFC15392 study baseline to last treatment of open-label extension study + 30 days

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