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Kidney Week

Abstract: INFO10-FR

A Phase 3 Clinical Program with the Novel Vasopressin V2 Receptor Antagonist Lixivaptan in Patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Session Information

  • Informational Posters - II
    November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

Authors

  • Shusterman, Neil H., Palladio Biosciences, Inc., Haverford, Pennsylvania, United States
  • Richardson, Elaine R., Palladio Biosciences, Inc., Haverford, Pennsylvania, United States
  • Castellana, John V., John Castellana Consulting, LLC, West Windsor, New Jersey, United States
  • Pellegrini, Lorenzo, Palladio Biosciences, Newtown, Pennsylvania, United States
Description

ADPKD is one of the most prevalent inherited genetic diseases of the kidney in humans. Recent advances establish vasopressin V2 receptor inhibition as a clinically validated mechanism of action for the treatment of ADPKD; however, safe and effective disease-modifying therapies for ADPKD are still lacking. Here we describe the clinical design and main elements of a registrational program with lixivaptan, a novel, potent vasopressin V2 antagonist, in patients with ADPKD.

PA-ADPKD-301 is a phase 3, double-blind, randomized, placebo-controlled multicenter study of lixivaptan in patients with ADPKD to be conducted globally. Approximately 2000 patients will be screened and 1200 randomized. Eligible patients will include adults aged 18–60 years with Chronic Kidney Disease (CKD) stages CKD2 and CKD3 and Mayo Clinic MRI Classification 1C, 1D, or 1E. After obtaining baseline assessments and completing a placebo run-in period, patients will be titrated on lixivaptan to achieve a tolerable dose that reduces first morning spot urine osmolality ≤250 mOsm/kg, and then randomized (2:1) to continue lixivaptan or receive matching placebo. After 52 weeks, treatment will be stopped, and final efficacy and safety assessments will be obtained. Study completers will be eligible to enter study PA-ADPKD-302, an open-label extension study that will study the safety and continued efficacy of lixivaptan during a second year of treatment.

The primary objectives of this clinical program are to characterize the efficacy and safety of lixivaptan in ADPKD patients. The primary efficacy endpoint is the change in eGFR from baseline to final assessment. The key safety objective is to compare the rate of liver function test elevations in patients treated with lixivaptan with those treated with placebo. Other assessments include total kidney volume and liver volume by MRI and eGFR slope.

Study PA-ADPKD-301 and its open label extension PA-ADPKD-302 are an important milestone toward the potential approval of lixivaptan as a safe and effective therapy for the treatment of ADPKD in a broad patient population.

Funding

  • Palladio Biosciences, Inc.