Cedirogant in adults with psoriasis: a phase II, randomized, placebo-controlled clinical trial

Abstract

Abstract Background Dysregulated interleukin (IL)-17/IL-23 signalling contributes to psoriasis pathogenesis. Cedirogant is an inverse agonist of nuclear receptor ROR-gamma isoform 2 (RORyt), a key transcription factor responsible for IL-17 synthesis and a regulator of the T helper 17 cell lineage programme. Objectives To evaluate the efficacy and safety of cedirogant to treat moderate-to-severe psoriasis. Methods In this phase IIb, multicentre, double-blind, 16-week study (NCT05044234), adults aged 18–65 years were randomized 1 : 1 : 1 : 1 to once-daily oral cedirogant 75 mg, 150 mg, 375 mg or placebo. Assessments included: ≥ 50%/75%/90%/100% improvement from baseline in Psoriasis Area and Severity Index (PASI 50/75/90/100), static Physician’s Global Assessment 0/1, Psoriasis Symptoms Scale 0 and improvements in itch; adverse events (AEs); pharmacokinetics; and IL-17A/F biomarker levels. Efficacy results based on observed cases were summarized descriptively. Results Of 156 enrolled patients, most were male (70.5%); 39 patients were randomized to each treatment. Only 47 patients completed the study; the study was terminated early owing to preclinical findings. At week 16, PASI 75 achievement rates (primary endpoint) were 29%, 8% and 42% in the cedirogant 75-mg, 150-mg and 375-mg groups, respectively, and 0% in the placebo group. AE rates were similar in the cedirogant 75-mg, 150-mg and placebo groups, and higher in the cedirogant 375-mg group; most AEs were mild or moderate. Conclusions Patients with psoriasis who received cedirogant showed PASI improvement, and cedirogant was generally well tolerated. The results should be interpreted in the context of early study termination. Cedirogant development has been discontinued.