Phase II Study of Single/Repeated Doses of Acumapimod (BCT197) to Treat Acute Exacerbations of COPD

References

• Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management and prevention of COPD; 2017 [cited 2018 Aug 9]. Available from: https://goldcopd.org/gold-2017-global-strategy-diagnosis-management-prevention-copd/
   Google Scholar
• World Health Organisation. The top 10 causes of death. Global Health Observatory data; 2017 [cited 2018 Aug 9]. Available from: http://www.who.int/gho/mortality_burden_disease/causes_death/top_10/en/
   Google Scholar
• Guarascio AJ, Ray SM, Finch CK, et al. The clinical and economic burden of chronic obstructive pulmonary disease in the USA. Clinicoecon Outcomes Res. 2013;5:235–245. doi:10.2147/CEOR.S34321.
   PubMedGoogle Scholar
• Criner GJ, Bourbeau J, Diekemper RL, et al. Executive summary: prevention of acute exacerbation of COPD: American College of Chest Physicians and Canadian Thoracic Society Guideline. Chest. 2015;147(4):883–893. doi:10.1378/chest.14-1676.
   PubMed Web of Science ®Google Scholar
• Suzuki M, Makita H, Ito YM, et al. Clinical features and determinants of COPD exacerbation in the Hokkaido COPD cohort study. Eur Respir J. 2014;43(5):1289–1297. doi:10.1183/09031936.00110213.
   PubMed Web of Science ®Google Scholar
• Hurst JR, Vestbo J, Anzueto A, et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med. 2010;363(12):1128–1138. doi:10.1056/NEJMoa0909883.
   PubMed Web of Science ®Google Scholar
• Ko FW, Chan KP, Hui DS, et al. Acute exacerbation of COPD. Respirology. 2016;21(7):1152–1165. doi:10.1111/resp.12780.
   PubMed Web of Science ®Google Scholar
• Barnes PJ. Corticosteroid resistance in patients with asthma and chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2013;131(3):636–645. doi:10.1016/j.jaci.2012.12.1564.
   PubMed Web of Science ®Google Scholar
• Herlaar E, Brown Z. p38 MAPK signalling cascades in inflammatory disease. Mol Med Today. 1999;5(10):439–447. doi:10.1016/S1357-4310(99)01544-0.
   PubMedGoogle Scholar
• Saklatvala J. The p38 MAP kinase pathway as a therapeutic target in inflammatory disease. Curr Opin Pharmacol. 2004;4(4):372–377. doi:10.1016/j.coph.2004.03.009.
   PubMed Web of Science ®Google Scholar
• Gaffey K, Reynolds S, Plumb J, et al. Increased phosphorylated p38 mitogen-activated protein kinase in COPD lungs. Eur Respir J. 2013;42(1):28–41. doi:10.1183/09031936.00170711.
   PubMed Web of Science ®Google Scholar
• Renda T, Baraldo S, Pelaia G, et al. Increased activation of p38 MAPK in COPD. Eur Respir J. 2008;31(1):62–69. doi:10.1183/09031936.00036707.
   PubMed Web of Science ®Google Scholar
• Escott KJ, Belvisi MG, Birrell MA, et al. Effect of the p38 kinase inhibitor, SB 203580, on allergic airway inflammation in the rat. Br J Pharmacol. 2000;131(2):173–176. doi:10.1038/sj.bjp.0703605.
   PubMed Web of Science ®Google Scholar
• Duan W, Chan JHP, McKay K, et al. Inhaled p38α mitogen-activated protein kinase antisense oligonucleotide attenuates asthma in mice. Am J Respir Crit Care Med. 2005;171(6):571–578. doi:10.1164/rccm.200408-1006OC.
   PubMed Web of Science ®Google Scholar
• Westra J, Doornbos-van der Meer B, de Boer P, et al. Strong inhibition of TNF-α production and inhibition of IL-8 and COX-2 mRNA expression in monocyte-derived macrophages by RWJ 67657, a p38 mitogen-activated protein kinase (MAPK) inhibitor. Arthritis Res Ther. 2004;6(4):R384. doi:10.1186/ar1204.
   PubMed Web of Science ®Google Scholar
• Armstrong J, Harbron C, Lea S, et al. Synergistic effects of p38 mitogen-activated protein kinase inhibition with a corticosteroid in alveolar macrophages from patients with chronic obstructive pulmonary disease. J Pharmacol Exp Ther. 2011;338(3):732–740. doi:10.1124/jpet.111.180737.
   PubMed Web of Science ®Google Scholar
• Khorasani N, Baker J, Johnson M, et al. Reversal of corticosteroid insensitivity by p38 MAPK inhibition in peripheral blood mononuclear cells from COPD. Int J Chron Obstruct Pulmon Dis. 2015;10:283–291. doi:10.2147/COPD.S72403.
   PubMed Web of Science ®Google Scholar
• Bhavsar P, Khorasani N, Hew M, et al. Effect of p38 MAPK inhibition on corticosteroid suppression of cytokine release in severe asthma. Eur Respir J. 2010;35(4):750–756. doi:10.1183/09031936.00071309.
   PubMed Web of Science ®Google Scholar
• Norman P. Investigational p38 inhibitors for the treatment of chronic obstructive pulmonary disease. Expert Opin Investig Drugs. 2015;24(3):383–392. doi:10.1517/13543784.2015.1006358.
   PubMed Web of Science ®Google Scholar
• Parkin J, Hardaker EL. Effects of acumapimod (BCT197), an oral p38 inhibitor, on tobacco smoke and lipopolysaccharide-induced lung inflammation in a corticosteroid-resistant rat COPD model. Am J Respir Crit Care Med. 2017;195:A6305. doi:10.1164/ajrccm-conference.2017.195.1_MeetingAbstracts.A6305.
   Web of Science ®Google Scholar
• De Buck S, Hueber W, Vitaliti A, et al. Population PK-PD model for tolerance evaluation to the p38 MAP kinase inhibitor BCT197. CPT Pharmacometrics Syst Pharmacol. 2015;4(12):691–700. doi:10.1002/psp4.12037.
   PubMedGoogle Scholar
• World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191–2194. doi:10.1001/jama.2013.281053.
   PubMed Web of Science ®Google Scholar
• Sivapalan P, Lapperre TS, Janner J, et al. Eosinophil-guided corticosteroid therapy in patients admitted to hospital with COPD exacerbation (CORTICO-COP): a multicentre, randomised, controlled, open-label, non-inferiority trial. Lancet Respir Med. 2019;7(8):699–709. doi:10.1016/S2213-2600(19)30176-6.
   PubMed Web of Science ®Google Scholar
• Gunen H, Hacievliyagil SS, Yetkin O, et al. The role of nebulised budesonide in the treatment of exacerbations of COPD. Eur Respir J. 2007;29(4):660–667. doi:10.1183/09031936.00073506.
   PubMed Web of Science ®Google Scholar
• Maltais F, Ostinelli J, Bourbeau J, et al. Comparison of nebulized budesonide and oral prednisolone with placebo in the treatment of acute exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial. Am J Respir Crit Care Med. 2002;165(5):698–703. doi:10.1164/ajrccm.165.5.2109093.
   PubMed Web of Science ®Google Scholar
• Miller MR, Hankinson J, Brusasco V, et al. Standardisation of spirometry. Eur Respir J. 2005;26(2):319–338. doi:10.1183/09031936.05.00034805.
   PubMed Web of Science ®Google Scholar
• Leidy NK, Wilcox TK, Jones PW, et al. Standardizing measurement of chronic obstructive pulmonary disease exacerbations. Reliability and validity of a patient-reported diary. Am J Respir Crit Care Med. 2011;183(3):323–329. doi:10.1164/rccm.201005-0762OC.
   PubMed Web of Science ®Google Scholar
• Davies L, Angus RM, Calverley P. Oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial. Lancet. 1999;354(9177):456–460. doi:10.1016/S0140-6736(98)11326-0.
   PubMed Web of Science ®Google Scholar
• MacNee W, Allan RJ, Jones I, et al. Efficacy and safety of the oral p38 inhibitor PH-797804 in chronic obstructive pulmonary disease: a randomised clinical trial. Thorax. 2013;68(8):738–745. doi:10.1136/thoraxjnl-2012-202744.
   PubMed Web of Science ®Google Scholar
• Abroug F, Ouanes I, Abroug S, et al. Systemic corticosteroids in acute exacerbation of COPD: a meta-analysis of controlled studies with emphasis on ICU patients. Ann Intensive Care. 2014;4:32. doi:10.1186/s13613-014-0032-x.
   PubMed Web of Science ®Google Scholar
• Walters JA, Tan DJ, White CJ, et al. Different durations of corticosteroid therapy for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2014;(12):CD006897. doi:10.1002/14651858.CD006897.pub4.
   PubMed Web of Science ®Google Scholar
• Walters JA, Wang W, Morley C, et al. Different durations of corticosteroid therapy for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2011;(10):CD006897. doi:10.1002/14651858.CD006897.pub2.
   PubMed Web of Science ®Google Scholar
• Leuppi JD, Schuetz P, Bingisser R, et al. Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinical trial. JAMA. 2013;309(21):2223–2231. doi:10.1001/jama.2013.5023.
   PubMed Web of Science ®Google Scholar
• Crisafulli E, Barbeta E, Ielpo A, et al. Management of severe acute exacerbations of COPD: an updated narrative review. Multidiscip Respir Med. 2018;13(1):36. doi:10.1186/s40248-018-0149-0.
   PubMedGoogle Scholar
• Barnes PJ. Inflammatory endotypes in COPD. Allergy. 2019;74(7):1249–1256. doi:10.1111/all.13760.
   PubMed Web of Science ®Google Scholar
• Camp J, Cane LJ, Bafadhel M. Shall we focus on the eosinophil to guide treatment with systemic corticosteroids during acute exacerbations of COPD?: PRO. Med Sci. 2018;6(3):pii: E74. doi:10.3390/medsci6030074.
   Google Scholar
• Watz H, Barnacle H, Hartley BF, et al. Efficacy and safety of the p38 MAPK inhibitor losmapimod for patients with chronic obstructive pulmonary disease: a randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2014;2(1):63–72. doi:10.1016/S2213-2600(13)70200-5.
   PubMed Web of Science ®Google Scholar
• Damjanov N, Kauffman RS, Spencer-Green GT. Efficacy, pharmacodynamics, and safety of VX-702, a novel p38 MAPK inhibitor, in rheumatoid arthritis: results of two randomized, double-blind, placebo-controlled clinical studies. Arthritis Rheum. 2009;60(5):1232–1241. doi:10.1002/art.24485.
   PubMed Web of Science ®Google Scholar
• Cohen SB, Cheng T-T, Chindalore V, et al. Evaluation of the efficacy and safety of pamapimod, a p38 MAP kinase inhibitor, in a double-blind, methotrexate-controlled study of patients with active rheumatoid arthritis. Arthritis Rheum. 2009;60(2):335–344. doi:10.1002/art.24266.
   PubMed Web of Science ®Google Scholar
• Hammaker D, Firestein GS. “Go upstream, young man”: lessons learned from the p38 saga. Ann Rheum Dis. 2010;69(Suppl 1):i77–82. doi:10.1136/ard.2009.119479.
   PubMed Web of Science ®Google Scholar
• Lomas DA, Lipson DA, Miller BE, et al. An oral inhibitor of p38 MAP kinase reduces plasma fibrinogen in patients with chronic obstructive pulmonary disease. J Clin Pharmacol. 2012;52(3):416–424. doi:10.1177/0091270010397050.
   PubMed Web of Science ®Google Scholar
• Xu JJ, Hendriks BS, Zhao J, et al. Multiple effects of acetaminophen and p38 inhibitors: towards pathway toxicology. FEBS Lett. 2008;582(8):1276–1282. doi:10.1016/j.febslet.2008.01.063.
   PubMed Web of Science ®Google Scholar
• Genovese MC, Cohen SB, Wofsy D, et al. A 24-week, randomized, double-blind, placebo-controlled, parallel group study of the efficacy of oral SCIO-469, a p38 mitogen-activated protein kinase inhibitor, in patients with active rheumatoid arthritis. J Rheumatol. 2011;38(5):846–854. doi:10.3899/jrheum.100602.
   PubMed Web of Science ®Google Scholar
• Ferguson GT, Beck B, Clerisme-Beaty E, et al. Recruiting patients after hospital discharge for acute exacerbation of COPD: challenges and lessons learned. Chronic Obstr Pulm Dis. 2017;4(4):265–278. doi:10.15326/jcopdf.4.4.2016.0176.
   PubMed Web of Science ®Google Scholar
• Parker CM, Voduc N, Aaron SD, et al. Physiological changes during symptom recovery from moderate exacerbations of COPD. Eur Respir J. 2005;26(3):420–428. doi:10.1183/09031936.05.00136304.
   PubMed Web of Science ®Google Scholar
• Leidy NK, Murray LT. Patient-reported outcome (PRO) measures for clinical trials of COPD: the EXACT and E-RS. COPD. 2013;10(3):393–398. doi:10.3109/15412555.2013.795423.
   PubMedGoogle Scholar
• Marks-Konczalik J, Costa M, Robertson J, et al. A post-hoc subgroup analysis of data from a six month clinical trial comparing the efficacy and safety of losmapimod in moderate-severe COPD patients with ≤2% and >2% blood eosinophils. Respir Med. 2015;109(7):860–869. doi:10.1016/j.rmed.2015.05.003.
   PubMed Web of Science ®Google Scholar
• Perera WR, Hurst JR, Wilkinson TMA, et al. Inflammatory changes, recovery and recurrence at COPD exacerbation. Eur Respir J. 2007;29(3):527–534. doi:10.1183/09031936.00092506.
   PubMed Web of Science ®Google Scholar