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 Vincent Loftus, Jr

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1014-1020
Number of pages7
JournalJournal of Crohn's and Colitis
Volume12
Issue number9
DOIs
StatePublished - Aug 29 2018

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Matrix Metalloproteinase Inhibitors
Matrix Metalloproteinase 9
Crohn Disease
Placebos
Subcutaneous Injections
Therapeutics
Abdominal Pain
Biomarkers
Clinical Trials
Safety
Antibodies

Keywords

  • Crohn's disease
  • inflammation
  • matrix metalloproteinase-9

ASJC Scopus subject areas

  • Gastroenterology

Cite this

A phase 2, randomized, placebo-controlled study evaluating matrix metalloproteinase-9 inhibitor, andecaliximab, in patients with moderately to severely active Crohn's disease. / Schreiber, Stefan; Siegel, Corey A.; Friedenberg, Keith A.; Younes, Ziad H.; Seidler, Ursula; Bhandari, Bal R.; Wang, Ke; Wendt, Emily; McKevitt, Matt; Zhao, Sally; Sundy, John S.; Lee, Scott D.; Loftus, Jr, Edward Vincent.

In: Journal of Crohn's and Colitis, Vol. 12, No. 9, 29.08.2018, p. 1014-1020.

Research output: Contribution to journalArticle

Schreiber, S, Siegel, CA, Friedenberg, KA, Younes, ZH, Seidler, U, Bhandari, BR, Wang, K, Wendt, E, McKevitt, M, Zhao, S, Sundy, JS, Lee, SD & Loftus, Jr, EV 2018, 'A phase 2, randomized, placebo-controlled study evaluating matrix metalloproteinase-9 inhibitor, andecaliximab, in patients with moderately to severely active Crohn's disease', Journal of Crohn's and Colitis, vol. 12, no. 9, pp. 1014-1020. https://doi.org/10.1093/ecco-jcc/jjy070
Schreiber, Stefan ; Siegel, Corey A. ; Friedenberg, Keith A. ; Younes, Ziad H. ; Seidler, Ursula ; Bhandari, Bal R. ; Wang, Ke ; Wendt, Emily ; McKevitt, Matt ; Zhao, Sally ; Sundy, John S. ; Lee, Scott D. ; Loftus, Jr, Edward Vincent. / A phase 2, randomized, placebo-controlled study evaluating matrix metalloproteinase-9 inhibitor, andecaliximab, in patients with moderately to severely active Crohn's disease. In: Journal of Crohn's and Colitis. 2018 ; Vol. 12, No. 9. pp. 1014-1020.
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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.",
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AU - Younes, Ziad H.

AU - Seidler, Ursula

AU - Bhandari, Bal R.

AU - Wang, Ke

AU - Wendt, Emily

AU - McKevitt, Matt

AU - Zhao, Sally

AU - Sundy, John S.

AU - Lee, Scott D.

AU - Loftus, Jr, Edward Vincent

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N2 - 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.

AB - 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.

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