Kidney Week

Abstract: PO1577

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

Session Information

• Cystic Kidney Diseases: Emerging Concepts, Biomarkers, and Clinical Trials
  October 22, 2020 | Location: On-Demand
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1001 Genetic Diseases of the Kidneys: Cystic

Authors

• Perrone, Ronald D., Division of Nephrology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, United States

Ronald D. Perrone,

• Hariri, Ali, Sanofi Genzyme, Cambridge, Massachusetts, United States

Ali Hariri,

• Minini, Pascal, Sanofi, Chilly Mazarin, France

Pascal Minini,

• Ahn, Curie, Department of Internal Medicine, Seoul National University, Seoul, Seoul, Korea (the Republic of)

Curie Ahn,

• Chapman, Arlene B., Department of Medicine, University of Chicago, Chicago, Illinois, United States

Arlene B. Chapman,

• Horie, Shigeo, Department of Urology, Juntendo University Graduate School of Medicine, Tokyo, Japan

Shigeo Horie,

• Knebelmann, Bertrand, Université Paris-Descartes, Faculté de Médecine, AP-HP, Service de Néphrologie, Hôpital Necker-Enfants Malades, Paris, France

Bertrand Knebelmann,

• Mrug, Michal, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States

Michal Mrug,

• Ong, Albert C., Department of Infection Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom

Albert C. Ong,

• Pei, York P., Division of Nephrology, University of Toronto, Toronto, Ontario, Canada

York P. Pei,

• Torres, Vicente E., Mayo Translational Polycystic Kidney Disease Center, Mayo Clinic, Rochester, Minnesota, United States

Vicente E. Torres,

• Modur, Vijay, Sanofi Genzyme, Cambridge, Massachusetts, United States

Vijay Modur,

• Gansevoort, Ron T., Department of Nephrology, University Medical Center Groningen, Groningen, Netherlands

Ron T. Gansevoort,

Background

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.

Methods

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 eGFR_CKD–EPI slope over 24 months in Stages 1 and 2 (n=560).

Results

Baseline characteristics for Stage 1 are shown (Table; n=225). Mean patient age is 42.7 years; mean eGFR_CKD–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.

Conclusion

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

Funding

• Commercial Support –