A new treatment for rhinovirus-induced symptoms in smokers
Research type
Research Study
Full title
A Phase 2, Single-Center, Double-Blind, Placebo-Controlled, Study of PUL-042 Inhalation Solution in Rhinovirus-induced Symptoms in Current Smokers with Gold Stage 0 Chronic Obstructive Pulmonary Disease (COPD)
IRAS ID
254008
Contact name
Onn Min Kon
Contact email
Sponsor organisation
Pulmotect Inc
Eudract number
2018-002806-30
Duration of Study in the UK
1 years, 0 months, 0 days
Research summary
Summary of Research
Pulmotect, Inc. is developing a novel therapeutic agent (PUL-042) to stimulate innate immunity in the lungs that may provide protection against lower respiratory tract infections. In the present study, we wish to determine if two doses of PUL-042 inhalation solution administered one day prior to challenge and on day two after challenge with an experimentally-introduced rhinovirus infection (HRV-A16) can prevent lower respiratory symptoms, lung function decreases, and reduce exacerbations in current smokers with GOLD stage 0 chronic obstructive pulmonary disease (COPD). This study will be a randomised double blind, placebo controlled Phase 2a clinical trial of 20 volunteers conducted at a single site, St Mary's Hospital in London. PUL-042 has been tested in two previous Phase 1 clinical trials that involved dose escalation studies. As an inhaled drug, PUL-042 was well tolerated and safe. Human rhinovirus strain HRVA-16 has been extensively used in clinical studies and also clinical trials involving healthy volunteers, smokers, asthmatics and COPD volunteers. Symptoms with HRV-A16 are generally mild and include sore throat, cough and runny nose. The study will involve a screening phase, one baseline clinical visit, and 14 clinical visits that will involve non-invasive sampling including bloods, nasal fluids, sputum and breathing tests. Volunteers will be asked to maintain a diary recording clinical and COPD specific symptoms over the study period that will not be longer than 10 weeks. Following experimental HRV-A16 challenge (Day 0), the volunteers will be followed up for 6 weeks (Day 42). If successful, PUL-042 may be a useful medicine for the treatment of COPD exacerbations, most of which are caused by virus infections.Summary of Results
This study (PUL-042-402) endeavoured to assess the safety, tolerability and efficacy of an inhaled combination of two Toll-like receptor agonists (PUL-042) in a human challenge model of rhinovirus infection. Healthy smokers with normal lung function were recruited from the community, dosed by inhalation (using a nebuliser) with PUL-042 or placebo on study day -1 and day 2, and infected with rhinovirus on study day 0. Subjects were followed up for 6 weeks post infection (day 42). The primary endpoint was changes in lower respiratory symptom score (by questionnaire) and secondary endpoints included changes in upper respiratory symptoms, nasal and sputum virus load, changes in blood biomarkers, lung bacterial load, adverse events and severe adverse events and changes in lung function. PUL-042 had no effect on the primary endpoint. PUL-042 treatment did not effect nasal or sputum virus load as measured as peak or area under the curve, but significantly reduced nasal virus load on day 6 post infection but not any other day. PUL-042 significantly increased blood neutrophils at 4h post infection on day -1 and day 2, which returned to normal within 24h. PUL-042 significantly reduced lung function (forced expiratory volume in one second) on day -1 and day 2 within 30 min, however lung function returned to normal within 24h post dose. The number of adverse events did not differ between PUL-042 and placebo. There were no severe adverse events in either group. Overall PUL-042 was considered safe and well tolerated.REC name
East Midlands - Nottingham 2 Research Ethics Committee
REC reference
18/EM/0311
Date of REC Opinion
5 Nov 2018
REC opinion
Further Information Favourable Opinion