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The composite Unified Huntington’s Disease Ratings Scale (cUHDRS) is a combined score of measures of motor function (TMS), cognition (SDMT and SWR) and overall functional capacity (TFC). The cUHDRS was developed to assess multi-domain clinical progression in Huntington’s disease (HD), and was shown to be a sensitive, reliable, and valid. To support its use in clinical studies, further evidence is required. This includes estimates of clinically meaningful change of the cUHDRS and its individual measures.To assess the reliability, validity and ability to detect change of the cUHDRS and to estimate minimal clinically meaningful within-patient cUHDRS change.Data from an early manifest HD population (TFC≥5) from two multi-national registries (ENROLL-HD and REGISTRY) were used. Test-retest reliability was assessed by calculating the intraclass correlation coefficient (ICC) in a subset of patients with no change in Clinical Global Impression of Severity (CGI-S) score. Convergent validity was assessed by Spearman rank order correlations. Known-groups validity was assessed by analysis of covariance (ANCOVA) between groups defined by CGI-S. Ability to detect change was assessed by ANCOVA comparing groups based on CGI-S score change. Regression analyses were conducted to estimate meaningful change, using CGI-S and Independence Scale (IS) as anchors.Strong evidence of test-retest reliability, known-groups validity and ability to detect change was demonstrated. Convergent validity was supported by stronger correlations with measures that are more similar. Meaningful within-patient change was estimated.cUHDRS is valid, reliable and able to detect change in patients with early manifest HD. Analyses anchored against CGI-S and IS support that a decline on the cUHDRS is clinically meaningful.Funded by F. Hoffmann-La Roche.