PGx7682 Exploratory Genetic Analysis for GSK2894512 for efficacy in atopic dermatitis patients in 203121

Trial description: GSK2894512 is a novel, non-steroidal, topical anti-inflammatory agent currently in parallel development for atopic dermatitis and psoriasis indications. Genetic samples are not available from the previous atopic dermatitis studies and study 203121 provides the first opportunity to assess the impact of genetic variation on response to GSK2894512 in patients with atopic dermatitis. These pharmacogenetic analyses are designed to assess if genetic variation influences response to GSK2894512 using data from study 203121. The primary endpoint is the proportion of subjects who have an Investigator Global Assessment (IGA) score of clear or almost clear (0 or 1) at week 12 and a minimum 2-grade improvement in IGA score from baseline to week 12.Two genetic analysis populations will be defined using subjects in the intent-to-treat (ITT) population of study 203121, who provided written informed consent for pharmacogenetic research, were successfully genotyped, and have valid clinical endpoint data available. The Genetics GSK2894512 population will include subjects who have received at least one dose of GSK2894512. The Genetics Vehicle population will include subjects who have received at least one dose of vehicle cream. The ITT population is comprised of all randomized subjects in study 203121.Genetic variation from across the genome and 14 pre-specified candidate gene variants, 7 in the FLG gene and 7 other variants associated with atopic dermatitis in a genome-wide association study, will be assessed in the Genetics GSK2894512 population using logistic regression models. The Genetics Vehicle population will be analyzed separately to aid in the interpretation of the Genetics GSK2894512 population results and to allow for estimation of genotype by treatment interactions using appropriate contrasts or linear combinations of the genetic effect size estimates obtained within the two genetic populations.