Safety, Pharmacokinetics, and Pharmacodynamics of CC‐90001 (BMS‐986360), a c‐Jun N‐terminal Kinase Inhibitor, in Phase 1 Studies in Healthy Participants

CC‐90001 selectively inhibits c‐Jun N‐terminal kinase (JNK), a stress‐activated protein implicated in fibrosis. In 3 phase 1 trials evaluating CC‐90001 pharmacokinetics, pharmacodynamics, and safety, healthy adults (N = 184) received oral CC‐90001 in a single dose (10–720 mg) or multiple doses (30–480 mg once daily for 7–18 days) or placebo. CC‐90001 was rapidly absorbed (median time to maximum concentration, 1–4 hours) and eliminated with a mean terminal elimination half‐life of 12–28 hours. Steady state was reached on day 5, with a mean accumulation ratio of 1.5‐ to 2‐fold following daily dosing. Exposure was similar in fed versus fasted participants and in Japanese versus non‐Japanese participants. CC‐90001 demonstrated dose‐ and exposure‐dependent inhibition of JNK as determined by histopathological analysis of c‐Jun phosphorylation in ultraviolet‐irradiated skin. The most common treatment‐emergent adverse events were nausea and headache; all were mild or moderate in intensity. Based on exposure‐response analysis using high‐quality electrocardiogram data, no clinically relevant QT prolongation liability for CC‐90001 was observed. Overall, single‐ and multiple‐dose CC‐90001 were generally safe and well tolerated at the tested doses and demonstrated JNK pathway engagement. These results support further clinical evaluation of CC‐90001.