Long-term Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) With Venglustat
Condition: Congenital Cystic Kidney Disease
MeSH terms: Kidney Diseases; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant; Kidney Diseases, Cystic
Intervention: Venglustat GZ402671
Intervention description: Pharmaceutical form: capsule Route of administration: oral
Intervention MeSH terms: Venglustat
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Primary 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 autosomal dominant
      polycystic kidney disease (ADPKD).

      Secondary Objective:

        -  To determine the effect of early versus delayed treatment with venglustat on the renal
           function (estimated glomerular filtration rate [eGFR] [Chronic Kidney Disease
           Epidemiology Collaboration {CKD-EPI} equation]).

        -  To characterize the safety profile of venglustat.

        -  To evaluate the effect of venglustat on the lens by ophthalmological examination.

        -  To evaluate the effect of venglustat on mood using Beck Depression Inventory-II
           (BDI-II).
    

Eligibility criteria:

        Inclusion criteria :

          -  Male or female adult with ADPKD who had completed the treatment period in Stage 1 or
             Stage 2 of Study EFC15392 (NCT03523728).

          -  The participants who had an eGFR >30 mL/min/1.73 m^2:

               1. 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.

               2. 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 used by men and women should be consistent with local regulations
             regarding the methods of contraception for those participating in clinical studies.

               1. Male participants who agreed 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.

               2. Female participants who had a negative urine pregnancy test at the Baseline visit
                  and 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 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.

        Exclusion criteria:

          -  For participants who had lag phase between the end of the EFC15392 study and Screening
             visit (Visit 0) in the LTS15823 study.

          -  The participant had a new 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.

          -  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 participant was 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 participant had received strong or moderate inducers or inhibitors of CYP3A4
             within 14 days or 5 half lives, whichever was 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 was 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 participant had the diagnosis
             of Gilbert syndrome. Participants with the Gilbert syndrome should had no additional
             symptoms or signs which suggest hepatobiliary disease and serum total bilirubin level
             no more than 3 milligrams per decilitre (mg/dL) (51 micromoles per litre [μmol/L])
             with conjugated bilirubin less than 20 percent (%) of the total bilirubin fraction.

        For participants with or without lag phase between the end of EFC15392 study and entry into
        LTS15823 study:

          -  The participant was pregnant or lactating.

          -  Presence of severe depression as measured by BDI-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.

        The above information was not intended to contain all considerations relevant to a
        participant's potential participation in a clinical trial.