PGx7689: an exploratory pharmacogenetic efficacy investigation of mepolizumab in subjects with COPD in studies 117106 and 117113

Trial description: Mepolizumab, SB-240563, is a humanized anti-interleukin5 (anti-IL5) antibody that binds to and inactivates IL-5, a cytokine that recruits and promotes activation and persistence of eosinophils in asthma exacerbations. Blocking IL-5 with mepolizumab has a positive effect in reducing the frequency of COPD exacerbations and eosinophilic inflammation in subjects with COPD who are dependent on systemic corticosteroids and/or antibiotics. The objective for study 208653 is to assess evidence of the influence of genome-wide variation on disease progression and efficacy of mepolizumab in subjects with COPD in studies MEA117106 and MEA117113.The Primary objectives are to identify genetic variants associated with disease progression in high stratum subjects treated with Placebo, to identify genetic variants associated with drug efficacy in high stratum subjects treated with mepolizumab, and to highlight genetic variants that are associated with both the disease progression and drug efficacy, or variants that are uniquely associated with either the disease progression or drug efficacy.The Primary endpoint, frequency of moderate and/or severe exacerbations (weeks 0-52), will be analyzed using a generalized linear model with negative binomial link function.The Secondary objectives are to identify genetic variants associated with disease progression in high stratum subjects treated with Placebo, to identify genetic variants associated with drug efficacy in high stratum subjects treated with mepolizumab, and to highlight genetic variants that are associated with both the disease progression and drug efficacy, or variants that are uniquely associated with either the disease progression or drug efficacy. The Secondary objective endpoint, frequency of COPD exacerbations requiring hospitalizations (weeks 0-52), will be analyzed using the same generalized linear model with negative binomial link function.The Exploratory objectives is to identify genetic associations between genetic variation and change from baseline mean total St. George’s Respiratory Questionnaire (SGRQ) score and categorical response in SGRQ score. Change from baseline mean total SGRQ score will be analyzed using a linear regression model. Response for SGRQ will be analyzed using logistic regression.