TY - JOUR T1 - Results of a phase 2a clinical trial with a peptide inhibitor of MARCKS protein indicate improvement of indices of bronchitis and lung function in patients with COPD JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - 4901 AU - Kenneth Adler AU - Monica Kraft AU - Indu Parikh AU - Edward Murphy AU - Andre Van As Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/4901.abstract N2 - A peptide inhibitor of MARCKS (BIO-11006) attenuates mucus hypersecretion, inflammatory cell influx and airway obstruction in several in vivo models of asthma and bronchitis, suggesting BIO-11006 as an ideal treatment for COPD. In a Phase 2a study, 172 subjects with stable COPD (GOLD Stage 2, 3) were randomized in a double blind, controlled safety and efficacy study. Four doses of BIO-11006 or control (half normal saline; HNS) were administered by nebulization for 21 days to 5 cohorts; 75 mg QD (n=38) or BID (n=24), 150 mg QD (n=35), and 125 mg BID (n=25); HNS (n=50). The ratio of active/control was 2:1 and 3:1 for QD and BID dosing, respectively. Trough FEV1 (primary endpoint) was measured on days 0, 3, 7, 14, 21, 28 and 49. A trend towards increased FEV1 with the 75mg BID group was maintained on follow-up days 28 and 49. An FEV1 responder analysis (defined as 5% or more improvement of FEV1 = Responder) revealed the percentages of responders for the 75 mg BID dose were 46, 38, 50 (p=0.014 vs HNS), 42, 54 (p=0.04 vs HNS) and 40% on days 3, 7, 14, 21, 28 and 49, respectively. BIO-11006 was systemically well tolerated with some increase in respiratory adverse events. We conclude that the 75 mg BID dose appeared to be the most efficacious by increasing the proportion of FEV1 responders statistically significantly as compared with HNS. Sputum volume and the St. Georges Respiratory Questionnaire Symptoms Score also trended towards improvement with 75mg BID. Thus, BIO-11006, a dual action molecule that decreases both mucus hypersecretion and inflammation, may represent a new advance in the treatment of COPD. ER -