Clinical and translational science, 2023-01, Vol.16 (1), p.151-164
2023
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- Autor(en) / Beteiligte
- Titel
- First‐in‐human study of deucravacitinib: A selective, potent, allosteric small‐molecule inhibitor of tyrosine kinase 2
- Ist Teil von
- Clinical and translational science, 2023-01, Vol.16 (1), p.151-164
- Ort / Verlag
- United States: John Wiley & Sons, Inc
- Erscheinungsjahr
- 2023
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- This randomized, double‐blind, single‐ and multiple‐ascending dose study assessed the pharmacokinetics (PKs), pharmacodynamics, and safety of deucravacitinib (Sotyktu™), a selective and potent small‐molecule inhibitor of tyrosine kinase 2, in 100 (75 active, 25 placebo) healthy volunteers (NCT02534636). Deucravacitinib was rapidly absorbed, with a half‐life of 8–15 h, and 1.4–1.9‐fold accumulation after multiple dosing. Deucravacitinib inhibited interleukin (IL)‐12/IL‐18‐induced interferon (IFN)γ production ex vivo in a dose‐ and concentration‐dependent manner. Following in vivo challenge with IFNα‐2a, deucravacitinib demonstrated dose‐dependent inhibition of lymphocyte count decreases and expression of 53 IFN‐regulated genes. There were no serious adverse events (AEs); the overall frequency of AEs was similar in the deucravacitinib (64%) and placebo (68%) groups. In this first‐in‐human study, deucravacitinib inhibited IL‐12/IL‐23 and type I IFN pathways in healthy volunteers, with favorable PK and safety profiles. Deucravacitinib is a promising therapeutic option for immune‐mediated diseases, including Crohn's disease, psoriasis, psoriatic arthritis, and systemic lupus erythematosus.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1752-8054eISSN: 1752-8062DOI: 10.1111/cts.13435Titel-ID: cdi_doaj_primary_oai_doaj_org_article_160d05762f494727925f54c50e945cba
- Format
- –
- Schlagworte
- Allosteric properties, Area Under Curve, Arthritis, Autoimmune Diseases - drug therapy, Cell number, Crohn's disease, Crohns disease, Dosage, Dose-Response Relationship, Drug, Double-Blind Method, Drug dosages, Enzyme inhibitors, FDA approval, Gene expression, Healthy Volunteers, Humans, Infections, Interleukin 12, Interleukin 18, Interleukin 23, Kinases, Laboratories, Light therapy, Lupus, Lymphocytes, Pharmacodynamics, Pharmacokinetics, Placebos, Protein-tyrosine kinase, Psoriasis, Psoriatic arthritis, Systemic lupus erythematosus, TYK2 Kinase - antagonists & inhibitors, Tyrosine Kinase Inhibitors - pharmacology, Tyrosine Kinase Inhibitors - therapeutic use, Volunteers, α-Interferon