AJM300, an Oral Antagonist of a4-Integrin, as induction therapy for patients with Moderately Active Ulcerative Colitis: A Phase 3, randomized, double-blind, placebo-controlled induction study

Abstract Background AJM300 (INN; carotegrast methyl), an orally active small molecule antagonist of the α4 subunit of α4β1/α4β7 integrins, demonstrated the efficacy and safety in patients with moderately active ulcerative colitis (UC) in a phase 2 study. The phase 3 study (NCT 03531892) of AJM300 as induction therapy was conducted in patients with moderately active UC. Methods Eligible patients were moderately active Japanese UC, defined as total Mayo Clinic scores (MCS) of 6–10, endoscopic subscores (ES) ≥2, and rectal bleeding subscores (RBS) ≥1, who had inadequate response or intolerance to oral 5-ASA. Followed by a 2-week single-blind placebo (PBO) run-in phase, patients were randomized 1:1 to receive AJM300 960 mg or PBO 3 times daily for 8 weeks. Responders or remitters were allowed to receive AJM300 960 mg again at the subsequent relapse (open-label). The primary endpoint was clinical response at week 8, defined as reduction of the MCS of ≥3-pts and ≥30%, reduction in RBS of ≥1-pt or RBS of ≤1, and ES ≤1. Results The randomized 203 patients had moderately active endoscopic evidence at baseline with median UC duration of 6.1 years and MCS of 7.8. For the primary endpoint, 45.1% (46/102) and 20.8% (21/101) of patients in the AJM300 and PBO groups, respectively, achieved clinical response at week 8 (OR=3.30 [95% CI, 1.73–6.29]; p=0.0003). Symptomatic remission, endoscopic improvement and endoscopic remission were also statistically significant for AJM300 vs PBO (Table). In case of episodic AJM300 treatment, AJM300 exhibited similar response to initial treatment. Overall, the incidence of AEs and serious AEs were similar between AJM300 and PBO. There were no deaths or cases of progressive multifocal leukoencephalopathy. Conclusion AJM300 induced clinical response as well as endoscopic remission with good tolerability. AJM300 may become a novel therapeutic option for patients who had inadequate response or intolerance to oral 5-ASA.