TY - JOUR T1 - 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 JF - The Journal of Rheumatology JO - J Rheumatol DO - 10.3899/jrheum.200893 SP - jrheum.200893 AU - Mark Genovese AU - Alberto Spindler AU - Akira Sagawa AU - Won Park AU - Anna Dudek AU - Alan Kivitz AU - Jeannie Chao AU - Melanie Lai Shan Chan AU - Jennifer Witcher AU - William Barchuk AU - Ajay Nirula Y1 - 2020/12/15 UR - http://www.jrheum.org/content/early/2021/01/12/jrheum.200893.abstract N2 - Objective 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). Methods 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. Results 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. Conclusion While no safety findings precluded continuation, the study was terminated after interim data demonstrated low likelihood of benefit in RA. ER -