Safety and Efficacy of Poseltinib, Bruton's Tyrosine Kinase-Inhibitor, in Patients With Rheumatoid Arthritis: A Randomized, Double-Blind, Placebo-Controlled, 2-Part Phase-2 Study. The Journal of rheumatology Genovese, M. n., Spindler, A. n., Sagawa, A. n., Park, W. n., Dudek, A. n., Kivitz, A. n., Chao, J. n., Chan, L. S., Witcher, J. n., Barchuk, W. n., Nirula, A. n. 2020


To evaluate efficacy and safety of poseltinib (formerly LY3337641/HM71224), an irreversible covalent inhibitor of Bruton's tyrosine kinase from a 2-part, Phase-2 trial (RAjuvenate) in adults with active rheumatoid arthritis (RA).In Part A, 36 patients with mildly active RA were randomized 1:1:1:1 to oral poseltinib 5-, 10-, or 30-mg or placebo once-daily for 4 weeks to assess safety/tolerability. No safety signals precluded moving to Part B where 250 patients with moderate-to-severe RA were randomized 1:1:1:1 to oral poseltinib 5- (N=63), 10- (N=62), or 30-mg (N=63) or placebo (N=62) once-daily for 12 weeks. Parts A and B permitted stable doses of background disease-modifying antirheumatic drugs. The primary endpoint in Part B was proportion of patients achieving 20% improvement in American College of Rheumatology criteria (ACR20) at Week 12. Logistic regression compared each poseltinib dose to placebo for primary/secondary endpoints. Nonresponder imputation was used for missing data.After interim analysis showed low likelihood of demonstrating significant efficacy, the sponsor discontinued Part B of the study. 189 (76%) patients completed 12 weeks in Part B; 61 discontinued study treatment (27 [44%] due to study termination by sponsor). There was no statistically significant difference in ACR20 response between any dose of poseltinib and placebo at Week 12 (p<0.05 for all comparisons). Five serious adverse events occurred (n=2, placebo; n=3, 30-mg); there was 1 death due to a fall.While no safety findings precluded continuation, the study was terminated after interim data demonstrated low likelihood of benefit in RA.

View details for DOI 10.3899/jrheum.200893

View details for PubMedID 33323529