Chronic obstructive pulmonary disease (COPD) is a significant cause of morbidity and
mortality worldwide. In contrast to other chronic diseases, COPD is increasing in prevalence
and is projected to be the third-leading cause of death and disability worldwide by 2030. The
costs to society for treating COPD are high, accounting for approximately 3.4% of the total
health care budget of the European Union. Acute exacerbations of COPD (AECOPD) are
responsible for a large portion of the economic burden of COPD. More than 500,000
hospitalisations and 100,000 deaths are attributed to AECOPD in the US each year. In addition
to a substantial economic burden, AECOPD is also responsible for much of the morbidity and
mortality from COPD.
Interleukin-33 (IL-33) is an alarmin released from the epithelium following damage. IL-33 is
an IL-1 family alarmin cytokine constitutively expressed at epithelial barrier surfaces where
it is rapidly released from cells during tissue injury. IL-33 signals through a receptor
complex of IL-1 receptor-like 1 (IL1RL1) (known as ST2) and IL-1 receptor accessory protein
(IL1RAcP) to initiate MyD88-dependent inflammatory pathways. The role of the IL33/ST2 axis in
COPD is uncertain. IL33 has been implicated in eosinophil recruitment to the airway and
maturation in the bone marrow largely via its effects upon innate lymphoid cells. IL33
increased following experimental cold in asthma and thus might play a role in the consequent
inflammatory response and possible susceptibility to secondary bacterial infection in
obstructive lung disease. Both eosinophilic inflammation and viral infection drive COPD
exacerbations and therefore targeting the IL33/ST2 axis might reduce COPD exacerbations.
The main aim of this trial is to evaluate whether anti-ST2 will impact on airway inflammation
in COPD and therefore reduce the frequency of exacerbations. For the purposes of this trial,
exacerbations are defined as flare-ups of symptoms involving the use of healthcare resulting
in treatment with steroids and/or antibiotics and/or hospitalisation or death due to COPD.
Phase:
Phase 2
Details
Lead Sponsor:
University of Leicester
Collaborators:
Biomedical Research Centre- Respiratory (Glenfield Hospital, Leicester UK) Genentech (South San Francisco, California, USA) Genentech, Inc. Leicester Clinical Trials Unit Respiratory Biomedical Research Centre (Glenfield Hospital, Leicester UK)