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Kidney Week

Abstract: PO1577

STAGED-PKD: An Enriched, Seamless, Two-Stage Study for Venglustat Assessment in ADPKD

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic


  • Perrone, Ronald D., Division of Nephrology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, United States
  • Hariri, Ali, Sanofi Genzyme, Cambridge, Massachusetts, United States
  • Minini, Pascal, Sanofi, Chilly Mazarin, France
  • Ahn, Curie, Department of Internal Medicine, Seoul National University, Seoul, Seoul, Korea (the Republic of)
  • Chapman, Arlene B., Department of Medicine, University of Chicago, Chicago, Illinois, United States
  • Horie, Shigeo, Department of Urology, Juntendo University Graduate School of Medicine, Tokyo, Japan
  • Knebelmann, Bertrand, Université Paris-Descartes, Faculté de Médecine, AP-HP, Service de Néphrologie, Hôpital Necker-Enfants Malades, Paris, France
  • Mrug, Michal, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Ong, Albert C., Department of Infection Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom
  • Pei, York P., Division of Nephrology, University of Toronto, Toronto, Ontario, Canada
  • Torres, Vicente E., Mayo Translational Polycystic Kidney Disease Center, Mayo Clinic, Rochester, Minnesota, United States
  • Modur, Vijay, Sanofi Genzyme, Cambridge, Massachusetts, United States
  • Gansevoort, Ron T., Department of Nephrology, University Medical Center Groningen, Groningen, Netherlands

Autosomal dominant polycystic kidney disease (ADPKD) occurs due to cyst formation and growth, resulting in increased total kidney volume (TKV) preceding kidney function decline by decades. The natural history of ADPKD complicates testing of new therapies. Venglustat, a glucosylceramide synthase inhibitor, inhibits cyst growth and reduces kidney failure in PKD mouse models. STAGED-PKD determines venglustat safety and efficacy and was designed using enrichment for progression to ESRD and extensive modeling from prior ADPKD trials.


STAGED-PKD is a two-stage (Phase 2/3), international, double-blind, randomized controlled trial in adults with ADPKD with increased TKV (Mayo Imaging Class 1C–1E) and eGFR 45–90 mL/min/1.73 m2. Target enrollment in Stages 1 and 2 is 240 and 320 patients, respectively. Stage 1 randomizes patients 1:1:1 to venglustat dose 1, dose 2 or placebo. Stage 2 randomizes patients 1:1 to placebo or venglustat preferred dose based on Stage 1 safety data. Primary endpoints are TKV growth rate over 18 months in Stage 1 and eGFRCKD–EPI slope over 24 months in Stages 1 and 2 (n=560).


Baseline characteristics for Stage 1 are shown (Table; n=225). Mean patient age is 42.7 years; mean eGFRCKD–EPI is 65.5 mL/min/1.73 m2. Overall, 55.1%, 30.7% and 14.2% are of Mayo Imaging Class 1C, 1D and 1E, respectively.


STAGED-PKD enables optimal dose selection and evaluation of venglustat safety and impact on TKV growth and eGFR slope in ADPKD. Stage 1 TKV assessment via a nested approach allows early efficacy evaluation, increasing trial design efficiency.

Stage 1 Baseline Characteristics


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