A phase 2, Randomized, Placebo-controlled Study Evaluating Matrix Metalloproteinase-9 Inhibitor, Andecaliximab, in Patients with Moderately to Severely Active Crohn’s Disease

A phase 2, Randomized, Placebo-controlled Study Evaluating Matrix Metalloproteinase-9 Inhibitor,... Abstract Background and Aims Matrix metalloproteinase-9 (MMP9) is implicated in the pathogenesis of Crohn’s disease and may serve as a potential biomarker. A phase 2 trial was conducted to examine the efficacy and safety of the anti-MMP9 antibody, andecaliximab (GS-5745), in patients with moderately to severely active Crohn’s disease. Methods Patients were randomized 1:2:2:2 to receive subcutaneous injections of placebo weekly (QW), andecaliximab 150 mg every 2 weeks (Q2W), andecaliximab 150 mg QW, or andecaliximab 300 mg QW. The coprimary study efficacy endpoints were evaluation of a clinical response, defined as liquid or very soft stool frequency and abdominal pain composite (from Patient-Reported Outcome 2) score ≤8 at week 8, and an endoscopic response, defined as a ≥50% reduction from baseline in the Simple Endoscopic Score for Crohn’s Disease, following 8 weeks of treatment. Results A total of 187 participants were randomized to treatment; 53 participants were randomized to each andecaliximab treatment group and 23 participants were randomized to placebo. Proportions of patients receiving andecaliximab were not different from proportions of patients receiving placebo based on clinical and endoscopic response and Crohn’s disease activity index defined remission at week 8. Rates of adverse events were comparable among andecaliximab and placebo. Conclusions Eight weeks of induction treatment with 150 mg andecaliximab Q2W, 150 mg andecaliximab QW, or 300 mg andecaliximab QW in patients with Crohn’s disease did not induce a clinically meaningful symptomatic or endoscopic response. Andecaliximab was well tolerated. Clinical trial registration ClinicalTrials.gov NCT02405442. Crohn’s disease, inflammation, matrix metalloproteinase-9 Copyright © 2018 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Crohn's and Colitis Oxford University Press

A phase 2, Randomized, Placebo-controlled Study Evaluating Matrix Metalloproteinase-9 Inhibitor, Andecaliximab, in Patients with Moderately to Severely Active Crohn’s Disease

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Publisher
Elsevier Science
Copyright
Copyright © 2018 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com
ISSN
1873-9946
eISSN
1876-4479
D.O.I.
10.1093/ecco-jcc/jjy070
Publisher site
See Article on Publisher Site

Abstract

Abstract Background and Aims Matrix metalloproteinase-9 (MMP9) is implicated in the pathogenesis of Crohn’s disease and may serve as a potential biomarker. A phase 2 trial was conducted to examine the efficacy and safety of the anti-MMP9 antibody, andecaliximab (GS-5745), in patients with moderately to severely active Crohn’s disease. Methods Patients were randomized 1:2:2:2 to receive subcutaneous injections of placebo weekly (QW), andecaliximab 150 mg every 2 weeks (Q2W), andecaliximab 150 mg QW, or andecaliximab 300 mg QW. The coprimary study efficacy endpoints were evaluation of a clinical response, defined as liquid or very soft stool frequency and abdominal pain composite (from Patient-Reported Outcome 2) score ≤8 at week 8, and an endoscopic response, defined as a ≥50% reduction from baseline in the Simple Endoscopic Score for Crohn’s Disease, following 8 weeks of treatment. Results A total of 187 participants were randomized to treatment; 53 participants were randomized to each andecaliximab treatment group and 23 participants were randomized to placebo. Proportions of patients receiving andecaliximab were not different from proportions of patients receiving placebo based on clinical and endoscopic response and Crohn’s disease activity index defined remission at week 8. Rates of adverse events were comparable among andecaliximab and placebo. Conclusions Eight weeks of induction treatment with 150 mg andecaliximab Q2W, 150 mg andecaliximab QW, or 300 mg andecaliximab QW in patients with Crohn’s disease did not induce a clinically meaningful symptomatic or endoscopic response. Andecaliximab was well tolerated. Clinical trial registration ClinicalTrials.gov NCT02405442. Crohn’s disease, inflammation, matrix metalloproteinase-9 Copyright © 2018 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Journal

Journal of Crohn's and ColitisOxford University Press

Published: May 29, 2018

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