Randomized Phase I Healthy Volunteer Study of UTTR1147A (IL‐22Fc): A Potential Therapy for Epithelial Injury

Most treatments for epithelial injury target hematopoietic mechanisms, possibly causing immunosuppression. Interleukin ( IL )‐22 promotes tissue regeneration, acting directly on epithelial cells. UTTR 1147A, a human IL ‐22Fc (immunoglobulin G (IgG)4) fusion protein, activates IL ‐22 signaling. This phase I placebo‐controlled trial of single, ascending, i.v. (1–120 μg/kg) and s.c (3–120 μg/kg) doses of UTTR 1147A analyzed its effects on safety, tolerability, pharmacokinetics, and pharmacodynamic biomarkers in healthy volunteers. Most adverse events ( AE s) were mild or moderate. The maximum tolerated i.v. dose in healthy volunteers was 90 μg/kg. Predominant AE s were dose‐dependent reversible skin effects consistent with IL ‐22 pharmacology. UTTR 1147A exposure increased approximately dose‐proportionally, with a half‐life of ~1 week. IL ‐22 biomarkers (regenerating islet protein 3A ( REG 3A), serum amyloid A ( SAA ), and C‐reactive protein ( CRP )) increased dose‐dependently. Neither inflammatory symptoms and signs nor cytokines increased with CRP elevations. UTTR 1147A demonstrated acceptable safety, pharmacokinetics, and IL ‐22R engagement, supporting further clinical development.