A Phase II, Two-Part, Randomised, Multi-Centre, Multinational, Double-Blind, Placebo-Controlled, Parallel Group Study to Compare the Efficacy and Safety of BCT197 when added on to Standard of Care for the Treatment of Acute Respiratory Exacerbations of Chronic Obstructive Pulmonary Disease Requiring Hospitalisation in Adults
Sponsor: Mereo BioPharma 1 Ltd
Development Phase: Phase IIa
Purpose: The purpose of this study is to compare the efficacy and safety of BCT197 when added on to standard of care in adult subjects with acute respiratory exacerbations of chronic obstructive pulmonary disease requiring hospitalization. Additionally, the study will characterize the pharmacokinetics of BCT197 in adults with COPD. The total duration of the study will be 26 weeks. Subjects will receive study treatment administration over a period of 5 days after randomization. The study is planned to enroll approximately 255 subjects internationally to complete the study.
Background: BCT197, is an inhibitor of the p38 mitogen-activated protein kinase (MAPK). BCT197 is a 5-amino-pyrazole representing one series in the chemically diverse class of p38 MAPK inhibitors. The p38 MAPK pathway is activated in a variety of inflammatory conditions and p38 MAPK inhibitors have been studied in a number of different diseases, including severe asthma, COPD, acute coronary syndrome and auto-immune diseases such as rheumatoid arthritis (RA), psoriasis and inflammatory bowel disease (IBD) (Kumar et al 2003, Lee and Dominguez 2005) but with limited success.
Inhibition of p38 MAPK has been shown to block release of inflammatory mediators both in vitro and in vivo. p38 MAPK regulates transcription through the phosphorylation of transcription factors involved in the inflammatory process such as ATF-2, p53, C/EBP- homologous protein, muscle-specific transcription factor-2 and STAT-1. Inhibition of p38 MAPK blocks TNF and IL-8 release by LPS-stimulated monocyte/macrophages, IL-6 release by bronchial epithelial cells in response to cigarette smoke and regulates a range of different neutrophil functions including adhesion, activation, chemotaxis and apoptosis. Moreover, increased phosphorylation of p38 has been demonstrated in the lungs of COPD patients (Renda et al 2008, Chin et al 2005). Therefore, a putative blockade of this pathway should result in attenuation of airway inflammation seen in acute exacerbations of COPD.
contact Bill Russell @ William.Russell@rutgers.edu for more
information. Recruitment for this study
will start 9/1/2016.