Safety and Efficacy of AJM300, an Oral Antagonist of α4 Integrin, in Induction Therapy for Patients With Active Ulcerative Colitis.
OBJECTIVE
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.
Tokyo Yamate Medical Center, Tokyo, Japan.
Naoki
N
Yoshimura
Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: mamoru.gast@tmd.ac.jp.
Mamoru
M
Watanabe
Sapporo-Kosei General Hospital, Sapporo, Japan.
Satoshi
S
Motoya
Dokkyo Medical University, Tochigi, Japan.
Keiichi
K
Tominaga
Tokyo Medical and Dental University, Tokyo, Japan.
Katsuyoshi
K
Matsuoka
Saga University, Saga, Japan.
Ryuichi
R
Iwakiri
Osaka City General Hospital, Osaka, Japan.
Kenji
K
Watanabe
Kitasato University, Kitasato Institute Hospital, Tokyo, Japan.
Toshifumi
T
Hibi
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D004311:Double-Blind Method; D006801:Humans; D039441:Integrin alpha4; D019804:Mesalamine / Q000627:therapeutic use; D012074:Remission Induction; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D039441:Integrin alpha4; D019804:Mesalamine
IBD; Integrin; Lymphocyte Trafficking; Randomized Clinical Trial