ERS 2019 – COPD clinical trials: new molecules and novel insights

  • Eliana Mesa
  • Conference Reports
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One study aimed to determine the impact of COPD symptom-related attacks on health-related quality of life (HRQoL) and the risk of moderate/severe exacerbations. For the evaluation of the HRQoL St George’s Respiratory Questionnaire (SGRQ) score post-attack was used and the average scores over 26 weeks were taken for patients without attacks. The relationship between attacks and moderate/severe exacerbations was evaluated with a time-dependent factor. The HRQoL was significantly worse for patients with any COPD symptom-related attacks. In addition, any attack elevated the risk of a subsequent moderate/severe exacerbations and the frequency of attacks increased the risk of a moderate/severe exacerbation.

A second lecture reviewed a randomised double-blind placebo-controlled trial which investigated the effect of dual bronchodilator therapy (glycopyrrolate/formoterol fumarate) on the increase of exercise tolerance during high-intensity constant work rate (CWR) cycle ergometry. The dual bronchodilator therapy increased exercise tolerance in COPD patients, with the greatest seen in severe COPD patients, and was accompanied by attenuated dynamic hyperinflation. Also, dead space ventilation (VD/VT) change did not alter the ventilatory requirement.

A post hoc analysis of the IMPACT study investigated whether a blood eosinophil count (BEC) measurement is sufficient to predict the inhaled corticosteroid (ICS) response in COPD.  Modelling the effect of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus UMEC/VI and FF/VI versus UMEC/VI on moderate/severe exacerbation rates using continuous BEC: there were two measurements taken, one at screening and the other at randomisation. The mean, minimum and maximum of the two values were taken. All models were comparable. Each of the BEC measurements substantially improved the model versus no measurement.  Although two BEC values do not appear to provide additional information to predict ICS response in COPD versus one value.

A prospective, multicentre study in 42 patients analysed the effectiveness of continuous treatment with oral azithromycin on pulmonary function and exercise tolerance in severe COPD, and its relation to systemic inflammation. After 3 months of treatment, a significant reduction in the rate of symptoms and exacerbations were observed. No functional changes were found, with the exception of an increase in PaO2, and no significant reductions in most of the inflammatory parameters were observed. Concluding that, continuous treatment with azithromycyn in severe COPD patients reduce symptoms and rates of exacerbations and improves functional status, related to a reduction in the inflammation.

A novel inhaled phosphodiesterase-4 inhibitor (PDE4i) -CHF6001-, has been evaluated in patients with moderate-to-severe COPD in a randomised, double-blind, double-dummy, 24-week study. Patients received either CHF6001 (800, 1600, 2400 or 3200µg daily), budesonide DPI 800µg daily or placebo add-on to maintenance therapy (formoterol 24µg). After 24 weeks of treatment, no significant difference versus placebo was observed on lung function for any treatment group. CHF6001 reduced the moderate/severe exacerbations rate versus placebo. The reduction was larger in the subgroup of chronic bronchitis patients. All CHF6001 doses were safe and well-tolerated and notably with regard to gastrointestinal side effects.

An ongoing study in COPD patients, without (Part 1) and with (Part 2) a confirmed respiratory virus infection has been designed to assess antiviral biomarker responses and clinical effects of inhaled IFN-β compared to placebo. In part 1, ten patients received three daily doses of IFN-β (6MIU) or placebo (8:2 ratio). Sputum cell gene expression (Mx1, OAS1, IFIT2, GBP1 and CXCL10) was determined. All antiviral biomarkers were significantly upregulated 24hrs post-dose compared to baseline (p

An observer-blind, controlled trial studied 40–80-year old COPD patients receiving two doses of a non-typeable Haemophilus influenzae (NTHi) adjuvanted vaccine (NTHi group, N=73) or placebo (Control group, N=72), 60 days apart. The vaccine efficacy was assessed (VE) against acute exacerbation of COPD (AECOPD) at multiple time points, time to first AECOPD and Hi presence in sputum. An overall trend towards a lower rate of exacerbations was observed in the NTHi group. The efficacy tended to be higher, with an onset of a first AECOPD after NTHi vaccination occurring later than in the control group; although the study was not powered to assess vaccine impact.

In the final lecture, a parallel-group, single-dose study reports the effect of ensifentrine (RPL554) administered by dry powder inhaler in patients with COPD. This is an investigational, first-in-class, inhaled dual inhibitor of the enzymes PDE 3 and 4 that combines bronchodilator and anti-inflammatory actions in a single compound. The study examined the bronchodilator effects, safety and tolerability of single-dose of ensifentrine (150, 500, 1500, 3000 and 6000 µg) vs placebo in 37 patients. An effective dose-dependent bronchodilatation was observed, with a mean change from baseline in the average and peak FEV-1 over 4 hours. There were no significant adverse events reported. Moreover, no statistical differences from placebo were found for heart or pulse rate for any ensifentrine dose.