Andecaliximab [Anti-matrix Metalloproteinase-9] Induction Therapy for Ulcerative Colitis: A Randomised, Double-Blind, Placebo-Controlled, Phase 2/3 Study in Patients With Moderate to Severe Disease.

Journal Article (Clinical Trial, Phase III;Journal Article)

BACKGROUND AND AIMS: Matrix metalloproteinase-9 [MMP9] is implicated in the pathogenesis of ulcerative colitis [UC] via disruption of intestinal barrier integrity and function. A phase 2/3 combined trial was designed to examine the efficacy, safety, and pharmacokinetics of the anti-MMP9 antibody, andecaliximab [formerly GS-5745], in patients with moderately to severely active UC. METHODS: Patients were randomised [1:1:1] to receive placebo, 150 mg andecaliximab every 2 weeks [Q2W], or 150 mg andecaliximab weekly [QW], via subcutaneous administration. The primary endpoint was endoscopy/bleeding/stool [EBS]-defined clinical remission [endoscopic subscore of 0 or 1, rectal bleeding subscore of 0, and at least a 1-point decrease from baseline in stool frequency to achieve a subscore of 0 or 1] at Week 8. The phase 2/3 trial met prespecified futility criteria and was terminated before completion. This study describes results from the 8-week induction phase. RESULTS: Neither 150 mg andecaliximab Q2W or QW resulted in a significant increase vs placebo in the proportion of patients achieving EBS clinical remission at Week 8. Remission rates [95% confidence intervals] were 7.3% [2.0%-17.6%], 7.4% [2.1%-17.9%], and 1.8% [0.0%-9.6%] in the placebo, andecaliximab Q2W, and andecaliximab QW groups, respectively. Similarly, Mayo Clinic Score response, endoscopic response, and mucosal [histological] healing did not differ among groups. Rates of adverse events were comparable among andecaliximab and placebo. CONCLUSIONS: Eight weeks of induction treatment with 150 mg andecaliximab in patients with UC did not induce clinical remission or response. Andecaliximab was well tolerated and pharmacokinetic properties were consistent with those previously reported.

Full Text

Duke Authors

Cited Authors

  • Sandborn, WJ; Bhandari, BR; Randall, C; Younes, ZH; Romanczyk, T; Xin, Y; Wendt, E; Chai, H; McKevitt, M; Zhao, S; Sundy, JS; Keshav, S; Danese, S

Published Date

  • August 29, 2018

Published In

Volume / Issue

  • 12 / 9

Start / End Page

  • 1021 - 1029

PubMed ID

  • 29767728

Pubmed Central ID

  • PMC6113706

Electronic International Standard Serial Number (EISSN)

  • 1876-4479

Digital Object Identifier (DOI)

  • 10.1093/ecco-jcc/jjy049

Language

  • eng

Conference Location

  • England