A Phase 2, Randomized, Placebo-Controlled Study Evaluating Matrix Metalloproteinase-9 Inhibitor, Andecaliximab, in Patients With Moderately to Severely Active Crohn's Disease

Stefan Schreiber, Corey A Siegel, Keith A Friedenberg, Ziad H Younes, Ursula Seidler, Bal R Bhandari, Ke Wang, Emily Wendt, Matt McKevitt, Sally Zhao, John S Sundy, Scott D Lee, Edward V Loftus, Stefan Schreiber, Corey A Siegel, Keith A Friedenberg, Ziad H Younes, Ursula Seidler, Bal R Bhandari, Ke Wang, Emily Wendt, Matt McKevitt, Sally Zhao, John S Sundy, Scott D Lee, Edward V Loftus

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 co-primary 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 28 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 the andecaliximab and placebo groups.

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.

Keywords: Crohn’s disease; inflammation; matrix metalloproteinase-9.

© The Author(s) 2018. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.

Figures

Figure 1.
Figure 1.
CONSORT diagram. Q2W, once every 2 weeks; QW, once weekly.
Figure 2.
Figure 2.
Proportion of patients achieving clinical response by [A] PRO2 score ≤ 8; [B] ≥ 50% baseline reduction in SES-CD; or [C] CDAI ≤ 150 at week 8. Bars denote 95% confidence interval. CDAI, Crohn’s Disease Activity Index; PRO2, Patient-Reported Outcome 2; Q2W, once every 2 weeks; QW, once weekly; SES-CD, Simple Endoscopic Score for Crohn’s Disease.

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