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

Summary: Icotrokinra (ICO), a first-in-class, targeted oral peptide that binds and inhibits the IL-23R, was evaluated in ICONIC-TOTAL (NCT06095102). This Phase 3 trial included plaque psoriasis (PsO) severity of BSA≥1%/IGA≥2, and employed a novel basket-like design to evaluate 3 cohorts of adults & adolescents (≥12-<18y) with at least moderate, difficult-to-treat, high-impact skin sites: scalp (ss-IGA≥3), genital (sPGA-G≥3), and/or hand/foot (hf-PGA≥3). 311 randomized pts (ICO=208/placebo [PBO]=103) with scalp (n=252), genital (n=140), and/or hand/foot (n=71) PsO received once-daily ICO 200mg or PBO through Week (W)16. Primary (IGA0/1: clear [0]/almost clear [1] & ≥2-grade improvement) and key secondary (ss-IGA0/1, sPGA-G0/1, hf-PGA0/1) endpoints were assessed at W16. ICO vs PBO met primary (IGA0/1: 57% vs 6%; P<0.001) and secondary (ss-IGA0/1 [66% vs 11%], sPGA-G0/1 [77% vs 21%]; both P<0.001) endpoints, and showed higher hf-PGA0/1 (42% vs 26%; P=0.144). Pt-reported scalp/genital PsO improvements were statistically significantly superior to PBO. Proportions of ICO & PBO pts with ≥1 AE were 50% & 42% (most common=nasopharyngitis) and GI AE were 7.2% & 7.8%, respectively. ICO demonstrated significantly higher rates of overall skin, scalp, and genital PsO clearance vs PBO with a favorable safety profile. Basket-like trial designs can be used to efficiently study special skin sites in pts with PsO and other diseases. Melinda J. Gooderham¹, Edward Lain², Robert Bissonnette³, Yu-Huei Huang⁴, Charles Lynde⁵, Matthias Hoffmann⁶, Eingun James Song⁷, Jessica H Rubens⁸, Amy M DeLozier⁸, Ming-Chun Hsu⁸, Richard B Warren⁹ 1. SKiN Ctr Derm, Queen's Univ, & Probity Med Res, Peterborough, ON, Canada. 2. Austin Inst Clin Res, Sanova Derm, Austin, TX, United States. 3. Innovaderm Res, Montreal, QC, Canada. 4. Chang Gung Mem Hosp & Chang Gung Univ, Taoyuan City, Taiwan. 5. Univ Toronto, Lynde Inst Derm & Lynderm Res Inc, Markham, ON, Canada. 6. Derm Practice Dr. M Hoffmann, Witten, Germany. 7. Frontier Derm, Mill Creek, WA, United States. 8. Johnson & Johnson, Spring House, PA, United States. 9. Derm Ctr, N Care Alliance NHS Found Trust & Div Musc & Derm Sci Manchester Acad Health Sci Ctr, Univ Manchester, Manchester, United Kingdom. Clinical Research: Interventional Research