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Selonsertib poses risk of AKI in patients with DKD

Presented by
Prof. Vlado Perkovic, University of New South Wales, Australia
ASN 2022
Phase 2, MOSAIC
Although selonsertib may slow kidney function decline in patients with diabetic kidney disease (DKD), a potential safety concern for acute kidney injury (AKI) was identified, which occurred in 11/100 patient-years compared to 5.9/100 patient-years with placebo [1].

Prof. Vlado Perkovic (University of New South Wales, Australia) presented the results of the phase 2b, randomised controlled MOSAIC trial (NCT04026165) of selonsertib in moderate to severe DKD. He first explained that selonsertib is a selective, small-molecule inhibitor of apoptosis signal-regulating kinase 1 that reduces inflammation, fibrosis, and apoptosis in the kidneys. “The aim of this trial was to evaluate whether selonsertib could slow kidney function decline in patients with DKD by using a novel trial design,” explained Prof. Perkovic. Key inclusion and exclusion criteria are outlined below (see Table).

Table: Inclusion and exclusion criteria

ACEi, angiotensin-converting enzyme inhibitors; ARB, angiotensin II receptor blocker; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; eGFRcr, creatinine-based estimated glomerular filtration rate; HbAc1, haemoglobin A1c; T2D, type 2 diabetes; UACR, urine albumin-to-creatinine ratio.

The primary endpoint of the study was creatinine-based estimated glomerular filtration rate (eGFRcr) slope from treatment-specific baseline to week 84 evaluated at a pre-specified 2-sided significance level of 0.30. A total of 310 patients were randomised to selonsertib (n=154) and placebo (n=156). Baseline characteristics were well balanced. “The mean difference in eGFRcr slope at week 84 between arms was 1.20 mL/min/1.73m2/year (95% CI −0.41 to 2.81; P=0.1439),” Prof. Perkovic said. “The primary endpoint was met at the pre-specified 2-sided significance level of 0.30.” “Regarding kidney clinical events (KCE), the absolute difference between the proportion of patients with KCE was 5% (95% CI −6% to 16%; P=0.1862),” continued Prof. Perkovic. The rate of adverse events (AEs) was high in the selonsertib arm (any treatment-emergent AE 218.8 patient-years vs 185.9 patient-years with placebo). The most common AE was AKI, which occurred in 11.0/100 patient-years with selonsertib versus 5.9/100 with placebo. Concluding, Prof. Perkovic noted that the small sample size and short follow-up limited further understanding of data on eGFRcr slope and KCE, and the acute effect of selonsertib on eGFRcr may impact the interpretation of some outcomes [1].

  1. Perkovic V, et al. A Phase 2b Randomized Controlled Trial of Selonsertib in Moderate to Severe Diabetic Kidney Disease (MOSAIC). FR-OR39, ASN Kidney Week 2022, 3–6 Nov.


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