Naoki Yoshimura1, Mamoru Watanabe2, Satoshi Motoya3, Keiichi Tominaga4, Katsuyoshi Matsuoka5, Ryuichi Iwakiri6, Kenji Watanabe7, Toshifumi Hibi8. 1. Tokyo Yamate Medical Center, Tokyo, Japan. 2. Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: mamoru.gast@tmd.ac.jp. 3. Sapporo-Kosei General Hospital, Sapporo, Japan. 4. Dokkyo Medical University, Tochigi, Japan. 5. Tokyo Medical and Dental University, Tokyo, Japan. 6. Saga University, Saga, Japan. 7. Osaka City General Hospital, Osaka, Japan. 8. Kitasato University, Kitasato Institute Hospital, Tokyo, Japan.
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.
RCT Entities:
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: Kenechukwu O Chudy-Onwugaje; Kaci E Christian; Francis A Farraye; Raymond K Cross Journal: Inflamm Bowel Dis Date: 2019-04-11 Impact factor: 5.325
Authors: Philipp Schreiner; Markus F Neurath; Siew C Ng; Emad M El-Omar; Ala I Sharara; Taku Kobayashi; Tadakazu Hisamatsu; Toshifumi Hibi; Gerhard Rogler Journal: Inflamm Intest Dis Date: 2019-07-09
Authors: Vipul Jairath; G Y Zou; Claire E Parker; John K MacDonald; Turki AlAmeel; Mohammad Al Beshir; Majid A Almadi; Talal Al-Taweel; Nathan Ss Atkinson; Sujata Biswas; Thomas Chapman; Parambir S Dulai; Mark A Glaire; Daniël R Hoekman; Andreas Koutsoumpas; Elizabeth Minas; Mahmoud H Mosli; Mark Samaan; Reena Khanna; Simon Travis; Geert D'Haens; William J Sandborn; Brian G Feagan Journal: Cochrane Database Syst Rev Date: 2017-09-08