Efficacy and safety of ABBV-154 in patients with moderately to severely active Crohn's disease: a phase 2b, randomized, double-blind, placebo-controlled trial.

Background: ABBV-154 is an antibody-drug conjugate of adalimumab and a proprietary glucocorticoid receptor modulator. This phase 2b randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of ABBV-154 versus placebo in patients with moderately to severely active Crohn's disease who had inadequate response to or were intolerant of prior biologic therapy. Methods: Patients were randomized 1:1:1:1:1 to ABBV-154 induction groups: 150 mg IV at week 0, then 80 mg SC at week 2 and every other week (EOW); 300 mg IV at week 0, then 230 mg SC at week 2 and EOW; 600 mg IV at week 0, then 530 mg SC at week 2 and EOW; 600 mg IV at week 0, then 530 mg SC at weeks 4 and 8, and placebo at weeks 2, 6, and 10; or placebo. The primary endpoint was achievement of endoscopic response per SES-CD by central review at week 12. Adverse events were monitored throughout. Results: Of 265 planned patients, 106 were randomized and treated until completion, discontinuation, or early study termination by the sponsor. At week 12, greater proportions of patients treated with ABBV-154 achieved endoscopic response versus placebo (7.1%, 33.3%, 28.6%, and 27.3% across the induction groups vs. 0%; data reported as observed). Adverse events were comparable across all ABBV-154 groups and slightly higher than placebo through week 12. Conclusions: ABBV-154 was well tolerated and demonstrated proof-of-concept for efficacy in patients with moderately to severely active Crohn's disease. Results should be interpreted with caution due to early study termination.