A Randomized, Placebo-Controlled Phase 2 Trial of CNTO 6785 in Chronic Obstructive Pulmonary Disease

Andreas Eich, Veronika Urban, Marek Jutel, Jiri Vlcek, Jae Jeong Shim, Vasiliy I. Trofimov, Chong Kin Liam, Ping Hung Kuo, Yanyan Hou, Jun Xiao, Patrick Branigan, Christopher D. O'Brien

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51 Citations (Scopus)

Abstract

Interleukin (IL)-17A may be an underlying factor in the pathophysiology of chronic obstructive pulmonary disease (COPD). Anti-IL-17 monoclonal antibodies have been used successfully in treating several immune-mediated inflammatory diseases. This phase 2, randomized, placebo-controlled, double-blind, parallel-group, proof-of-concept study is the first clinical study evaluating the efficacy and safety of the anti-IL-17A monoclonal antibody CNTO 6785 in patients with symptomatic moderate-to-severe COPD. Patients were treated with CNTO 6785 (n = 93) or placebo (n = 94) intravenously at Weeks 0, 2, and 4 (induction), then Weeks 8 and 12, and followed till Week 24. The primary efficacy endpoint was the change from baseline in pre-bronchodilator percent-predicted forced expiratory volume in 1 second at Week 16. Samples were collected at all visits for pharmacokinetic (PK) evaluation, and standard safety assessments were performed. The mean difference in the primary efficacy endpoint between CNTO 6785 and placebo was not statistically significant (−0.49%; p = 0.599). No other efficacy endpoints demonstrated clinically or statistically significant differences with CNTO 6785 compared with placebo. CNTO 6785 was generally well tolerated; no major safety signals were detected. The most frequently reported treatment-emergent adverse events were infections and infestations; however, no notable differences were observed between CNTO 6785 and placebo in terms of rates of infections. PK results suggested that the steady state of serum CNTO 6785 concentration was reached within 16 weeks. These results suggest that IL-17A is unlikely to be a dominant driver in the pathology of, or a viable therapeutic target for, COPD. ClinicalTrials.gov Identifier: NCT01966549; EudraCT Identifier: 2012-003607-36.

Original languageEnglish
Pages (from-to)476-483
Number of pages8
JournalCOPD: Journal of Chronic Obstructive Pulmonary Disease
Volume14
Issue number5
DOIs
Publication statusPublished - 2017 Sept 3
Externally publishedYes

Bibliographical note

Funding Information:
The authors would like to acknowledge all the investigators who participated in the study: Alina Agafyina (Russia), Zsolt Andrasofszky (Hungary), Olga Barbarash (Russia), Ekkehard Beck (Germany), Andreas Eich (Germany), Katalin Gomori (Hungary), Svetlana Goncharova (Russia), Roslan Harun (Malaysia), Julia Ilkovich (Russia), Gabriele Illies (Germany), Kwang Ho In (Republic of Korea), Ahmad Izuanuddin Ismail (Malaysia), Daniela Kopecka (Czech Republic), Alex Kroker (Germany), Ping-Hung Kuo (Taiwan), Igor Leshchenko (Russia), Chong Kin Liam (Malaysia), Anneliese Linnhoff (Germany), Gyorgy Losonczy (Hungary), Danuta Madra-Rogacka (Poland), Jaroslav Mares (Czech Republic), Irmgard Marten (Germany), Mat Zuki Mat Jaeb (Malaysia), Harald Mueller-Pawlowski (Germany), Jaromir Musil (Czech Republic), Piotr Napora (Poland), Marta Papp (Hungary), Kwang Joo Park (Republic of Korea), Norbert Pauk (Czech Republic), Heymer Peter (Germany), Grazyna Pulka (Poland), Judit Schlezak (Hungary), Jae Jeong Shim (Republic of Korea), Irena Spasova (Czech Republic), Ewa Springer (Poland), Vasiliy Trofimov (Russia), Irina Tseimakh (Russia), Veronika Urban (Hungary), Zsuzsanna Vecsey (Hungary), Jiri Vlcek (Czech Republic), Lutz Volgmann (Germany), Henrik Watz (Germany), Suk Joong Yong (Republic of Korea), and Vladimir Zindr (Czech Republic). The study described in this manuscript was sponsored by Janssen Research & Development, LLC. Medical writing support was provided by Allison Michaelis, PhD, of MedErgy, and was funded by Janssen Global Services, LLC.

Funding Information:
The study described in this manuscript was sponsored by Janssen Research & Development, LLC. Medical writing support was provided by Allison Michaelis, PhD, of MedErgy, and was funded by Janssen Global Services, LLC.

Publisher Copyright:
© 2017 The Author(s). Published with license by Taylor & Francis Group, LLC © 2017, © Andreas Eich, Veronika Urban, Marek Jutel, Jiri Vlcek, Jae Jeong Shim, Vasiliy I. Trofimov, Chong-Kin Liam, Ping-Hung Kuo, Yanyan Hou, Jun Xiao, Patrick Branigan and Christopher D. O'Brien.

Keywords

  • Antibodies
  • forced expiratory volume
  • interleukin-17
  • monoclonal
  • safety

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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