AJM300 (Carotegrast Methyl), an Oral Antagonist of α4-Integrin, as Induction Therapy for Patients with Moderately Active Ulcerative Colitis: A Multicentre, Randomised, Double-Blind, Placebo-Controlled Phase 3 Study

Background: AJM300 is an oral, small-molecule α4-integrin antagonist. We assessed the efficacy and safety of AJM300 in patients with moderately active ulcerative colitis (UC).Methods: This randomised, double-blind, placebo-controlled study allocated patients 1:1 to receive either AJM300 (960 mg) or placebo with a Mayo Clinic score (MCS) of 6–10, endoscopic subscores (ES) ≥ 2, rectal bleeding subscores (RBS) ≥ 1, and an inadequate response/intolerance to at least 5-aminosalicylic acid (5-ASA). The study drug was administered orally, three times daily for eight weeks, and continued for up to 24 weeks if endoscopic remission or disappearance of rectal bleeding was not achieved. The primary endpoint was clinical response (reduction in MCS of ≥ 30% and ≥ 3 points, reduction in RBS of ≥ 1 point or RBS of ≤ 1, and ES of ≤ 1) at week 8. The efficacy and safety of re-treatment with AJM300 in patients who relapsed after an initial response to AJM300 were also evaluated. Findings: Between June 2018 and May 2021, 203 patients were randomised (102 to AJM300 and 101 to placebo). The proportions of clinical responses at week 8 in the AJM300 and placebo groups were 45·1% and 20·8%, respectively (odd ratio = 3·30, 95% confidence interval, 1·73−6·29) (P = 0·0003). The incidence of adverse events was similar between AJM300 and placebo (38·2% vs 38·6%). Twenty-six patients who relapsed after AJM300 treatment were re-treated with AJM300 , with a clinical response rate of 73·1%. There was no difference in the incidence of adverse events even with repeated administration.Interpretation: AJM300 was well tolerated and effectively induced a clinical response in moderately active UC patients who had an inadequate response or intolerance to at least 5-ASA. Re-treatment with AJM300 may be effective.Funding Statement: This study was funded by EA Pharma Co., Ltd. and Kissei Pharmaceutical Co., Ltd.Clinical Trial Registration Details: Clinicaltrials.gov: NCT03531892.Declaration of Interests: K. Matsuoka has received research support and lecture/consulting fees from AbbVie, EA Pharma, Mitsubishi Tanabe Pharma, Mochida, Kyorin, Kissei, Astellas Pharma, JIMRO, Janssen, Pfizer, Takeda, Zeria, Gilead Sciences, Miyarisan, Nippon Kayaku, Celltrion Healthcare, Eli Lilly; M. Watanabe has received research support and lecture/consulting fees from AbbVie GK., EA Pharma Co., Ltd., Mitsubishi Tanabe Pharma, Mochida, Kyorin, Kissei, JIMRO, Janssen, Pfizer, Takeda, Zeria, Gilead Sciences, Miyarisan, Nippon Kayaku, Celltrion Healthcare, Eli Lilly; T. Ohmori has received research support and lecture/consulting fees from Mochida, Janssen, Mitsubishi Tanabe Pharma, Takeda, Daiichi Sankyo, Otsuka, Olympus Corporation, JIMRO, Kyorin, EA Pharma; K. Nakajima, T. Ishida, Y. Ishiguro, K. Kanke, K. Kobayashi has nothing to disclose; F. Hirai has received research support and lecture/consulting fees from Abbvie, EA Pharma Co, Janssen, Mochida, Mitsubishi Tanabe Pharma, Takeda; K. Watanabe has received research support and lecture/consulting fees from Mitsubishi Tanabe, Takeda, AbbVie, EA Pharma, Kissei, Pfizer, Kyorin, Mochida, Zeria, JIMRO, Otsuka, Asahi Kasei; H. Mizusawa has received research support and lecture/consulting fees from EA Pharma; S. Kishida has received research support and lecture/consulting fees from EA Pharma; Y. Miura has nothing to disclose; A. Ohta and T. Kajioka are employees of EA Pharma; T. Hibi has received research support and lecture/consulting fees from Aspen, EA Pharma, AbbVie, JIMRO, Zeria, Otsuka, Mitsubishi Tanabe Pharma, Kyorin, Janssen, Mochida, Takeda, Gilead Sciences, Celltrion Healthcare, Nippon Kayaku, Kissei, Ferring, Eli Lilly, Pfizer, Nichi-Iko, Nippon Kayaku, Bristol-Myers Squibb.Ethics Approval Statement: All patients gave written informed consent before initiation of any study-specific procedures. The study was conducted in accordance with the ethical principles originating in or derived from the Declaration of Helsinki, and Good Clinical Practice guidelines. The study was designed and conducted by the sponsor in collaboration with the principal investigators. EA Pharma Co., Ltd. monitored study conduct, collected the data, and performed the statistical analyses.