Effect of the inhaled PDE4 inhibitor CHF6001 on biomarkers of inflammation in COPD
Abstract Background CHF6001 is a novel inhaled phosphodiesterase-4 inhibitor. This Phase IIa study assessed the effects of CHF6001 on markers of inflammation in induced sputum and blood in patients with chronic obstructive pulmonary disease (COPD). Methods This was a multicentre, three-period (each...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-08-01
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| Series: | Respiratory Research |
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| Online Access: | http://link.springer.com/article/10.1186/s12931-019-1142-7 |
| _version_ | 1818326764740411392 |
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| author | Dave Singh Kai Michael Beeh Brendan Colgan Oliver Kornmann Brian Leaker Henrik Watz Germano Lucci Silvia Geraci Aida Emirova Mirco Govoni Marie Anna Nandeuil |
| author_facet | Dave Singh Kai Michael Beeh Brendan Colgan Oliver Kornmann Brian Leaker Henrik Watz Germano Lucci Silvia Geraci Aida Emirova Mirco Govoni Marie Anna Nandeuil |
| author_sort | Dave Singh |
| collection | DOAJ |
| description | Abstract Background CHF6001 is a novel inhaled phosphodiesterase-4 inhibitor. This Phase IIa study assessed the effects of CHF6001 on markers of inflammation in induced sputum and blood in patients with chronic obstructive pulmonary disease (COPD). Methods This was a multicentre, three-period (each 32 days), three-way, placebo-controlled, double-blind, complete-block crossover study. Eligible patients had COPD, chronic bronchitis, and were receiving inhaled triple therapy for ≥2 months. Patients received CHF6001 800 or 1600 μg, or matching placebo twice daily via multi-dose dry-powder inhaler (NEXThaler). Induced sputum was collected pre-dose on Day 1, and post-dose on Days 20, 26 and 32. Blood was sampled pre-dose on Day 1, and pre- and post-dose on Day 32. Results Of 61 randomised patients, 54 (88.5%) completed the study. There were no significant differences between groups for overall sputum cell count, or absolute numbers of neutrophils, eosinophils or lymphocytes. CHF6001 800 μg significantly decreased the absolute number and percentage of macrophages vs placebo. In sputum, compared with placebo both CHF6001 doses significantly decreased leukotriene B4, C-X-C motif chemokine ligand 8, macrophage inflammatory protein 1β, matrix metalloproteinase 9, and tumour necrosis factor α (TNFα). In blood, both CHF6001 doses significantly decreased serum surfactant protein D vs placebo. CHF6001 1600 μg significantly decreased TNFα ex-vivo (after incubation with lipopolysaccharide). Conclusion The data from this study show that CHF6001 inhaled twice daily has anti-inflammatory effects in the lungs of patients with COPD already treated with triple inhaled therapy. Trial registration The study is registered on ClinicalTrials.gov (NCT03004417). |
| first_indexed | 2024-12-13T12:05:34Z |
| format | Article |
| id | doaj.art-01259f933c6244f7abadad184d308298 |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-12-13T12:05:34Z |
| publishDate | 2019-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-01259f933c6244f7abadad184d3082982022-12-21T23:46:58ZengBMCRespiratory Research1465-993X2019-08-0120111210.1186/s12931-019-1142-7Effect of the inhaled PDE4 inhibitor CHF6001 on biomarkers of inflammation in COPDDave Singh0Kai Michael Beeh1Brendan Colgan2Oliver Kornmann3Brian Leaker4Henrik Watz5Germano Lucci6Silvia Geraci7Aida Emirova8Mirco Govoni9Marie Anna Nandeuil10Medicines Evaluation Unit, The University of Manchester, Manchester University NHS Foundation TrustInsaf Respiratory Research InstituteCelerionIKF Pneumologie Frankfurt, Clinical Research Centre Respiratory DiseasesThe Heart Lung CentrePulmonary Research Institute at Lung Clinic Grosshansdorf, Airway Research Center North, Member of the German Center for Lung ResearchGlobal Clinical Development, ChiesiGlobal Clinical Development, ChiesiGlobal Clinical Development, ChiesiGlobal Clinical Development, ChiesiGlobal Clinical Development, ChiesiAbstract Background CHF6001 is a novel inhaled phosphodiesterase-4 inhibitor. This Phase IIa study assessed the effects of CHF6001 on markers of inflammation in induced sputum and blood in patients with chronic obstructive pulmonary disease (COPD). Methods This was a multicentre, three-period (each 32 days), three-way, placebo-controlled, double-blind, complete-block crossover study. Eligible patients had COPD, chronic bronchitis, and were receiving inhaled triple therapy for ≥2 months. Patients received CHF6001 800 or 1600 μg, or matching placebo twice daily via multi-dose dry-powder inhaler (NEXThaler). Induced sputum was collected pre-dose on Day 1, and post-dose on Days 20, 26 and 32. Blood was sampled pre-dose on Day 1, and pre- and post-dose on Day 32. Results Of 61 randomised patients, 54 (88.5%) completed the study. There were no significant differences between groups for overall sputum cell count, or absolute numbers of neutrophils, eosinophils or lymphocytes. CHF6001 800 μg significantly decreased the absolute number and percentage of macrophages vs placebo. In sputum, compared with placebo both CHF6001 doses significantly decreased leukotriene B4, C-X-C motif chemokine ligand 8, macrophage inflammatory protein 1β, matrix metalloproteinase 9, and tumour necrosis factor α (TNFα). In blood, both CHF6001 doses significantly decreased serum surfactant protein D vs placebo. CHF6001 1600 μg significantly decreased TNFα ex-vivo (after incubation with lipopolysaccharide). Conclusion The data from this study show that CHF6001 inhaled twice daily has anti-inflammatory effects in the lungs of patients with COPD already treated with triple inhaled therapy. Trial registration The study is registered on ClinicalTrials.gov (NCT03004417).http://link.springer.com/article/10.1186/s12931-019-1142-7Induced sputumInflammationPhosphodiesterase 4 inhibitorsPharmacologyChronic obstructive pulmonary disease |
| spellingShingle | Dave Singh Kai Michael Beeh Brendan Colgan Oliver Kornmann Brian Leaker Henrik Watz Germano Lucci Silvia Geraci Aida Emirova Mirco Govoni Marie Anna Nandeuil Effect of the inhaled PDE4 inhibitor CHF6001 on biomarkers of inflammation in COPD Respiratory Research Induced sputum Inflammation Phosphodiesterase 4 inhibitors Pharmacology Chronic obstructive pulmonary disease |
| title | Effect of the inhaled PDE4 inhibitor CHF6001 on biomarkers of inflammation in COPD |
| title_full | Effect of the inhaled PDE4 inhibitor CHF6001 on biomarkers of inflammation in COPD |
| title_fullStr | Effect of the inhaled PDE4 inhibitor CHF6001 on biomarkers of inflammation in COPD |
| title_full_unstemmed | Effect of the inhaled PDE4 inhibitor CHF6001 on biomarkers of inflammation in COPD |
| title_short | Effect of the inhaled PDE4 inhibitor CHF6001 on biomarkers of inflammation in COPD |
| title_sort | effect of the inhaled pde4 inhibitor chf6001 on biomarkers of inflammation in copd |
| topic | Induced sputum Inflammation Phosphodiesterase 4 inhibitors Pharmacology Chronic obstructive pulmonary disease |
| url | http://link.springer.com/article/10.1186/s12931-019-1142-7 |
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