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Abstract: FR-OR39

A Phase 2b Randomized Controlled Trial of Selonsertib in Moderate to Severe Diabetic Kidney Disease (MOSAIC)

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Perkovic, Vlado, University of New South Wales, Sydney, New South Wales, Australia
  • Tuttle, Katherine R., University of Washington and Providence Health Care, Spokane, Washington, United States
  • Pergola, Pablo E., Renal Associates PA, San Antonio, Texas, United States
  • Mahaffey, Kenneth W., Stanford Center for Clinical Research, Stanford University, Stanford, California, United States
  • Patel, Uptal D., Gilead Sciences Inc, Foster City, California, United States
  • Ishida, Julie H., Gilead Sciences Inc, Foster City, California, United States
  • Chen, Fang, Gilead Sciences Inc, Foster City, California, United States
  • Crans, Gerald, Gilead Sciences Inc, Foster City, California, United States
  • Kustra, Robert, Gilead Sciences Inc, Foster City, California, United States
  • Trivedi, Mona, Gilead Sciences Inc, Foster City, California, United States
  • L Heerspink, Hiddo Jan, University Medical Center, University of Groningen, Groningen, Netherlands
  • Rossing, Peter, Kobenhavns Universitet, Kobenhavn, Denmark
  • Kashihara, Naoki, Kawasaki Ika Daigaku, Kurashiki, Okayama, Japan
  • Chertow, Glenn, Stanford Center for Clinical Research, Stanford University, Stanford, California, United States
Background

Selonsertib (SEL) is an apoptosis signal-regulating kinase 1 inhibitor that reduces inflammation, fibrosis, and apoptosis. The MOSAIC study evaluated whether SEL could slow decline in kidney function in patients with diabetic kidney disease (DKD).

Methods

We conducted a Phase 2b study in adults with type 2 diabetes mellitus and eGFR 20-<60 mL/min/1.73m2 with UACR 150-5000 mg/g on an ACEi or ARB. To account for the acute decrease in eGFRcr associated with SEL initiation, following placebo (PBO), all patients entered a 4-week SEL run-in period to establish treatment-specific baseline eGFRs (Fig 1). Patients were randomized 1:1 to SEL 18 mg or PBO once daily for ≥48 weeks. The primary efficacy endpoint was eGFRcr slope from treatment-specific baselines to Week 84, evaluated at a 2-sided significance level of 0.30. Kidney clinical events (KCE; eGFRcr ≥40% decline from pre-run-in baseline, kidney failure, or death due to kidney disease) and adverse events (AEs) were evaluated.

Results

Overall, 310 patients were randomized (SEL n=154, PBO n=156; 68% male, 52% white, mean age 65 years, 18% SGLT-2i use at randomization, and mean baseline eGFRcr 35.0 mL/min/1.73m2). The mean difference in eGFRcr slope at Week 84 between arms was 1.20 mL/min/1.73m2/year (95% CI, -0.41, 2.81; p=0.14) (Fig 2). KCEs occurred in 17% (26/154) of the SEL arm and 12% (19/156) in PBO (difference, 5%; 95% CI, -6%, 16%; p=0.19). The most common AE was acute kidney injury (AKI) (SEL, 11.0/100 patient-years [PY]; PBO, 5.9/100 PY).

Conclusion

The study met the primary efficacy endpoint, suggesting that SEL may slow kidney function decline in diabetic kidney disease, although a potential safety concern for AKI was identified.

Fig. 1. Study design

Fig 2. Change in eGFRcr from treatment-specific baselines through Week 84

Funding

  • Commercial Support –