Safety and Efficacy of AJM300, an Oral Antagonist of α4 Integrin, in Induction Therapy for Patients With Active Ulcerative Colitis.

Abstract

BACKGROUND & AIMS:

AJM300 is an orally active small-molecule antagonist of the α4 integrin subunit. We performed a randomized trial to investigate the efficacy and safety of AJM300 in patients with active ulcerative colitis (UC).

METHODS:

In a double-blind, placebo-controlled, phase 2a study, 102 patients with moderately active UC (Mayo Clinic scores of 6-10, endoscopic subscores ≥2, and rectal bleeding subscores ≥1) who had inadequate response or intolerance to mesalamine or corticosteroids were randomly assigned to receive AJM300 (960 mg) or placebo 3 times daily for 8 weeks. The primary end point was a clinical response at week 8, defined as a decrease in Mayo Clinic score of at least 3 points and a decrease of at least 30% from baseline, with a decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1.

RESULTS:

Clinical response rates were 62.7% and 25.5% at week 8 in the AJM300 group and placebo group, respectively (odds ratio [OR] = 5.35; 95% confidence interval [CI]: 2.23-12.82; P = .0002). Rates of clinical remission (Mayo Clinic score ≤2 and no subscore >1) were 23.5% and 3.9% in the AJM300 group and placebo groups, respectively (OR = 7.81; 95% CI: 1.64-37.24; P = .0099), and rates of mucosal healing (endoscopic subscores of 0 or 1) were 58.8% and 29.4% (OR = 4.65; 95% CI: 1.81-11.90; P = .0014). No serious adverse event, including progressive multifocal leukoencephalopathy, was observed, although more investigations are needed to confirm the safety profile of this drug.

CONCLUSIONS:

AJM300 was well tolerated and more effective than placebo in inducing clinical response, clinical remission, and mucosal healing in patients with moderately active UC. ClinicalTrials.jp no: JapicCTI-132293.

• Authors: Naoki Yoshimura, Mamoru Watanabe, Satoshi Motoya, Keiichi Tominaga, Katsuyoshi Matsuoka, Ryuichi Iwakiri, Kenji Watanabe, Toshifumi Hibi, AJM300 Study Group
• Journal: Gastroenterology (Gastroenterology) Vol. 149 Issue 7 Pg. 1775-1783.e2 (Dec 2015) ISSN: 1528-0012 [Electronic] United States
• PMID: 26327130 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Comment)
• Copyright: Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Chemical References

• Adrenal Cortex Hormones
• Integrin alpha4
• Mesalamine

Topics

• Adrenal Cortex Hormones (therapeutic use)
• Colitis, Ulcerative (drug therapy)
• Double-Blind Method
• Humans
• Integrin alpha4
• Mesalamine (therapeutic use)
• Remission Induction
• Treatment Outcome