Dataset Information

Anti-MAdCAM-1 antibody (PF-00547659) for active refractory Crohn's disease in Japanese and Korean patients: the OPERA study.

ABSTRACT: BACKGROUND/AIMS:PF-00547659 is a monoclonal antibody against human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) that prevents the binding of ?4?7+ lymphocytes to MAdCAM-expressing sites in the gastrointestinal tract with high affinity and selectivity, and is being developed for the treatment of Crohn's disease (CD). METHODS:OPERA is a randomized, multicenter, double-blind, placebo-controlled study to investigate the efficacy, safety, and pharmacokinetics of PF-00547659 following subcutaneous administration in subjects with active CD, a history of failure or intolerance to anti-tumor necrosis factor and/or immunosuppressants, high-sensitivity C-reactive protein > 3.0 mg/L, and ulcers on colonoscopy. The primary endpoint was Crohn's Disease Activity Index-70 response at week 8 or 12. Subpopulation analyses for Asian subjects were performed as some differences are observed in genetics and clinical phenotypes in Asian CD patients compared with Western patients. RESULTS:In this study, 265 CD subjects were randomized, with a subpopulation of 21 subjects (8 Japanese and 13 Korean) defined as the Asian population. In the overall and Asian populations; PF-00547659 was pharmacologically active as evidenced by soluble MAdCAM and circulating ?7+ central memory CD4+ T-lymphocytes, although no clear evidence of efficacy was observed in any clinical endpoints; pharmacokinetics of PF-00547659 in the Asian subpopulation was generally comparable to the overall population; and the safety profile of PF-00547659 appeared acceptable up to 12 weeks of treatment. CONCLUSIONS:In the overall and Asian populations, efficacy of PF-00547659 could not be demonstrated using any clinical endpoints compared with placebo. Pharmacokinetics and safety of PF-00547659 were generally comparable. Further studies with larger numbers of patients are required to confirm our results. (Trial Registration Number: NCT01276509).

SUBMITTER: Saruta M

PROVIDER: S-EPMC7000638 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Anti-MAdCAM-1 antibody (PF-00547659) for active refractory Crohn's disease in Japanese and Korean patients: the OPERA study.

Saruta Masayuki M Park Dong Il DI Kim Young-Ho YH Yang Suk-Kyun SK Jang Byung-Ik BI Cheon Jae Hee JH Im Jong Pil JP Kanai Takanori T Katsuno Tatsuro T Ishiguro Yoh Y Nagaoka Makoto M Isogawa Naoki N Li Yinhua Y Banerjee Anindita A Ahmad Alaa A Hassan-Zahraee Mina M Clare Robert R Gorelick Kenneth J KJ Cataldi Fabio F Watanabe Mamoru M Hibi Toshifumi T

Intestinal research 20200130 1

<h4>Background/aims</h4>PF-00547659 is a monoclonal antibody against human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) that prevents the binding of α4β7+ lymphocytes to MAdCAM-expressing sites in the gastrointestinal tract with high affinity and selectivity, and is being developed for the treatment of Crohn's disease (CD).<h4>Methods</h4>OPERA is a randomized, multicenter, double-blind, placebo-controlled study to investigate the efficacy, safety, and pharmacokinetics of PF-00547659 fo ...[more]

PMID: 32013314

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Dataset Information

Anti-MAdCAM-1 antibody (PF-00547659) for active refractory Crohn's disease in Japanese and Korean patients: the OPERA study.

Publications

Anti-MAdCAM-1 antibody (PF-00547659) for active refractory Crohn's disease in Japanese and Korean patients: the OPERA study.

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