0555: Phase 3 Results From an Innovative Trial Design of Treating Plaque Psoriasis Involving Difficult-to-Treat, High-Impact Sites With Icotrokinra, a Targeted Oral Peptide That Selectively Inhibits the IL-23–Receptor

Background/Purpose: Icotrokinra (ICO), a first-in-class, targeted oral peptide that binds and inhibits the interleukin (IL)-23R, was evaluated in ICONIC-TOTAL (NCT06095102).

Methods: This Phase 3 trial included plaque psoriasis (PsO) severity of body surface area (BSA) ≥1%/Investigator’s Global Assessment (IGA) ≥2 and employed a novel basket-like design to evaluate 3 cohorts of adults & adolescents (≥12 to < 18 years) with at least moderate, difficult-to-treat, high-impact skin sites: scalp (scalp-specific [ss]-IGA ≥3), genital (static Physician Global Assessment of Genitalia [sPGA-G] ≥3), and/or hand/foot (hf-PGA ≥3). Primary (IGA 0/1: clear [0]/almost clear [1] & ≥2-grade improvement) and key secondary (ss-IGA 0/1, sPGA-G 0/1, hf-PGA 0/1) endpoints were assessed at Week 16.

Results: 311 randomized patients (ICO=208/placebo=103) with scalp (n=252), genital (n=140), and/or hand/foot (n=71) PsO received once-daily ICO 200 mg or placebo through Week 16. ICO vs placebo met primary (IGA 0/1: 57% vs 6%; P< 0.001) and scalp and genital key secondary endpoints (ss-IGA 0/1: 66% vs 11%; sPGA-G 0/1: 77% vs 21%; both P< 0.001), and showed higher hf-PGA 0/1 (42% vs 26%; P=0.144). Patient-reported scalp and genital PsO improvements were statistically significantly superior to placebo. Proportions of ICO and placebo patients with ≥1 adverse event (AE) were 50% & 42% (the most commonly reported AE was nasopharyngitis) and GI AE were 7.2% & 7.8%, respectively.

Conclusion: ICO demonstrated significantly higher rates of overall skin, scalp, and genital PsO clearance vs placebo with a favorable safety profile. Basket-like trial designs can be used to efficiently study special skin sites in patients with PsO and other diseases.