In:
Clinical Pharmacology & Therapeutics, Wiley, Vol. 105, No. 1 ( 2019-01), p. 177-189
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0009-9236
,
1532-6535
DOI:
10.1002/cpt.2019.105.issue-1
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
2040184-X
SSG:
15,3