Abstract
BackgroundA subset of COPD-patients presents with eosinophilic airway inflammation. While treatment of asthmatic patients with the GATA3-specific DNAzyme SB010 attenuated sputum eosinophilia after allergen challenge, this specific treatment has not been evaluated in patients with COPD. Our objective was to evaluate the feasibility and safety of inhaled SB010 in COPD patients with sputum eosinophilia.MethodsWe conducted a randomized, double-blind, placebo-controlled, multicentre clinical trial in COPD-patients with sputum eosinophilia (≥2.5% non-squamous cells). Patients inhaled 10 mg SB010 bid or matching placebo via the controlled inhalation system AKITA2 APIXNEB for 28 days. Endpoints included the feasibility of the study (primary), patient’s safety, sputum eosinophils, FENO, lung function, symptoms, and biomarkers. The study was registered in the German Clinical Trials Register: DRKS00006087.ResultsOne hundred thirty patients were screened, 23 patients were randomized (FEV1 49.4 ± 11.5%; sputum eosinophils 8.0 ± 8.4%) and 19 patients completed the study (10 placebo, 9 SB010. After 28 days, SB010 decreased the relative sputum eosinophil count (p = 0.004) as compared to no changes in placebo-treated patients. FENO, lung function, and symptoms were not affected significantly. We found an increase in blood IFN-γ (p = 0.02) and a trend to lower IL-5 levels in patients treated with SB010. SB010 was safe and well tolerated. Thirty five AEs (22 SB010, 13 placebo including 1 SAE) were observed with 3 AEs in each group judged to be possibly treatment-related.ConclusionIn patients with eosinophilic COPD, sputum eosinophils could be reduced by inhalation of SB010. Long-term studies are needed to demonstrate clinical efficacy.
Highlights
A subset of Chronic obstructive pulmonary disease (COPD)-patients presents with eosinophilic airway inflammation
The three most important reasons for screening failure were missing sputum eosinophilia (n = 104), inability to inhale via the AKITA2 APIXNEB inhalation system (n = 17) and a post-bronchodilator lung function not meeting the inclusion criteria (FEV1/Forced vital capacity (FVC) < 0.7; Forced expiratory volume in one second (FEV1) 30–80% predicted; n = 9)
Immunglobulin E (IgE) levels were higher in the Placebo group, while patients treated with Drug formulation of hgd40 for inhaled application (SB010) were slightly more eosinophilic (Table 1)
Summary
A subset of COPD-patients presents with eosinophilic airway inflammation. Our objective was to evaluate the feasibility and safety of inhaled SB010 in COPD patients with sputum eosinophilia. The zinc finger transcription factor GATA3 activates type 2 helper T cells (Th2 cells), leading to an increased production of interleukins- (IL) 4, 5, and 13 [8, 9]. The same transcription factor GATA3 acts in type 2 innate lymphoid cells (ILC2 cells) and leads to a production of a similar, even though not identical cytokine pattern, including IL-5, IL-13 and, to a lesser extent, IL-4 [12,13,14], which might mediate airway eosinophilia in nonallergic asthma and COPD [15]. In a recently published study, the anti-IL-5 monoclonal antibody mepolizumab led to a significant reduction of exacerbations in COPD patients with an elevated baseline blood eosinophil count [16]
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