For patients with ulcerative colitis (UC) who had inadequate response to mesalazine, AJM300 (carotegrast methyl), a small-molecule α4-integrin antagonist, could be a novel induction therapy option, according to study findings published in The Lancet Gastroenterology and Hepatology.
Researchers conducted a randomized, double-blind, placebo-controlled clinical trial (ClinicalTrials.gov Identifier: NCT03531892) at 82 centers in Japan. Between 2018 and 2020, a total of 203 patients with moderately active UC were enrolled for the phase 3 study. All study participants had an inadequate response or intolerance to oral sulfasalazine, pentasa, asacol, or lialda. The trial included a placebo run-in period, treatment phase, and an open-label retreatment phase in the event of relapse during the 52-week follow-up.
Patients were randomly assigned 1:1 to receive 960 mg AJM300 (n=102) or placebo (n=101) administered orally 3 times daily for 8 weeks, continued up to 24 weeks if endoscopic remission or rectal bleeding was not resolved. The primary endpoint was clinical response at 8 weeks, as defined as 30% or greater reduction in Mayo Clinic score and 1 point or higher reduction in rectal bleeding score.
Among study participants, 61% were men, the mean age was 43.4±13.7 years, 58% had Mayo Clinic score 8 to 10, and average disease duration was 6.1±5.6 years.
Most patients (87%) completed the 8-week treatment period and 50% entered the extension period. A total of 2 of the AJM300 and 3 of the placebo recipients continued on therapy to week 24. Relapses occurred among 25 of the AJM300 and 12 of the placebo cohorts, and these patients entered the retreatment phase. The interim analysis found the median time to relapse was 297 days after remission.
AJM300 was associated with greater clinical response at weeks 8 (c2, 13.56; P =.00023) and 24 (c2, 15.18; P <.0001), symptomatic remission at weeks 8 (c2, 8.84; P =.0029) and 24 (c2, 9.63%; P =.0019), endoscopic improvement at weeks 8 (c2, 16.66; P <.0001) and 24 (c2, 15.45; P <.0001), and endoscopic remission at weeks 8 (c2, 7.65; P =.0057) and 24 (c2, 3.87; P =.049). AJM300 did not associate with significant clinical remission at weeks 8 (P =.11) or 24 (P =.056).
Starting at week 4, AJM300 associated with significantly higher proportions of patients achieving rectal bleeding disappearance (all P £.0037). Response as measured by the partial Mayo Clinic score differed significantly between active and control treatment starting at week 2 (all P £.0039).
Over a third of the AJM300 and placebo cohorts reported an adverse event (38% vs 39%), and 18% of both groups experienced a treatment-related adverse event. The most common adverse event was nasopharyngitis (10% vs 11%).
The major limitation of this study was the small sample sizes among the cohorts of patients who received treatment continuation or retreatment. A large-scale, long-term, post-marketing surveillance study is needed to establish AJM300 as a novel induction therapy.
“AJM300 was effective and safe when it was re-administered to patients whose disease relapsed after treatment with AJM300,” the study authors wrote. “AJM300 was well tolerated, and most adverse events were mild to moderate and manageable. AJM300 could be a novel option for induction therapy in patients with moderately active [UC], who have an inadequate response or intolerance to oral mesalazine.”
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Matsuoka K, Watanabe M, Ohmori T, et al. 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. Lancet Gastroenterol Hepatol. Published online March 30, 2022. doi:10.1016/S2468-1253(22)00022-X