Journal: Journal of Neurology

Article Title: Challenges in multinational rare disease clinical studies during COVID-19: regulatory assessment of cipaglucosidase alfa plus miglustat in adults with late-onset Pompe disease

doi: 10.1007/s00415-024-12843-x

Figure Lengend Snippet: Change from baseline to week 52 in a 6MWD and b sitting % predicted FVC (ITT population excluding outlier). In the original analysis, values for change from baseline to week 52 were based on LOCF data. p values were nominal two sided. The post hoc analysis used MMRM with actual time points of assessments in the ITT-OBS population. The number of patients in the post hoc analysis depended on the number of patients with non-missing values for the analysis. In all analyses, results exclude one patient judged likely to have deliberately underperformed at baseline. a As the 6MWD data were not normally distributed, the p value for 6MWD was from non-parametric ANCOVA as prespecified; b For sitting % predicted FVC, the p value in the original analysis was from ANCOVA as prespecified. 6MWD 6-min walk distance, alg + pbo alglucosidase alfa plus placebo, ANCOVA analysis of covariance, CI confidence interval, cipa + mig cipaglucosidase alfa plus miglustat, FVC forced vital capacity, ITT intent to treat, ITT-OBS ITT population with observed values, LOCF last observation carried forward, LS least squares, MMRM mixed-effect model for repeated measures

Article Snippet: 6MWD 6-min walk distance, alg + pbo alglucosidase alfa plus placebo, ANCOVA analysis of covariance, CI confidence interval, cipa + mig cipaglucosidase alfa + miglustat, FVC forced vital capacity, GSGC Gait, Stairs, Gowers’ Maneuver, Chair, ITT intent to treat, ITT-OBS ITT population with observed values, LOCF last observation carried forward, LS least squares, MMRM mixed-effect model for repeated measures, MMT manual muscle test, PROMIS Patient-Reported Outcomes Measurement Information System

Techniques:

Journal: Journal of Neurology

Article Title: Challenges in multinational rare disease clinical studies during COVID-19: regulatory assessment of cipaglucosidase alfa plus miglustat in adults with late-onset Pompe disease

doi: 10.1007/s00415-024-12843-x

Figure Lengend Snippet: LS mean treatment difference for change from baseline to week 52 for the primary and key secondary endpoints (ITT population excluding outlier). Data shown are LS mean treatment differences. Error bars indicate 95% CI. In the original analysis, change from baseline to week 52 are LOCF means, and LS mean differences were based on ANCOVA models adjusting for baseline covariates except for 6MWD, which used non-parametric ANCOVA and differed slightly from the mean differences shown in Fig. for 6MWD and sitting % predicted FVC. The post hoc analysis used MMRM with actual time points of assessments in the ITT-OBS population. a For these endpoints, a negative change from baseline indicates an improvement, and axis values have been reversed. 6MWD 6-min walk distance, alg + pbo alglucosidase alfa plus placebo, ANCOVA analysis of covariance, CI confidence interval, cipa + mig cipaglucosidase alfa + miglustat, FVC forced vital capacity, GSGC Gait, Stairs, Gowers’ Maneuver, Chair, ITT intent to treat, ITT-OBS ITT population with observed values, LOCF last observation carried forward, LS least squares, MMRM mixed-effect model for repeated measures, MMT manual muscle test, PROMIS Patient-Reported Outcomes Measurement Information System

Article Snippet: 6MWD 6-min walk distance, alg + pbo alglucosidase alfa plus placebo, ANCOVA analysis of covariance, CI confidence interval, cipa + mig cipaglucosidase alfa + miglustat, FVC forced vital capacity, GSGC Gait, Stairs, Gowers’ Maneuver, Chair, ITT intent to treat, ITT-OBS ITT population with observed values, LOCF last observation carried forward, LS least squares, MMRM mixed-effect model for repeated measures, MMT manual muscle test, PROMIS Patient-Reported Outcomes Measurement Information System

Techniques:

Journal: Journal of Neurology

Article Title: Challenges in multinational rare disease clinical studies during COVID-19: regulatory assessment of cipaglucosidase alfa plus miglustat in adults with late-onset Pompe disease

doi: 10.1007/s00415-024-12843-x

Figure Lengend Snippet: LS mean treatment difference for change from baseline to week 52 for the primary and key secondary endpoints in a ERT-experienced and b ERT-naïve patients. Data shown are LS mean treatment difference. Error bars indicate 95% CI. In the original analysis, change from baseline to week 52 were LOCF means. LS mean differences were based on analysis models adjusting for baseline covariates. The post hoc analysis used MMRM with actual time points of assessments in the ITT-OBS population. a For these endpoints, a negative change from baseline indicates an improvement, and axis values have been reversed. 6MWD 6-min walk distance, alg + pbo alglucosidase alfa plus placebo, CI confidence interval, cipa + mig cipaglucosidase alfa plus miglustat, ERT enzyme replacement therapy, FVC forced vital capacity, GSGC Gait, Stairs, Gowers’ Maneuver, Chair, ITT-OBS intent-to-treat population with observed values, LOCF last observation carried forward, LS least squares, MMRM mixed-effect model for repeated measures, MMT manual muscle test, PROMIS Patient-Reported Outcomes Measurement Information System

Article Snippet: 6MWD 6-min walk distance, alg + pbo alglucosidase alfa plus placebo, ANCOVA analysis of covariance, CI confidence interval, cipa + mig cipaglucosidase alfa + miglustat, FVC forced vital capacity, GSGC Gait, Stairs, Gowers’ Maneuver, Chair, ITT intent to treat, ITT-OBS ITT population with observed values, LOCF last observation carried forward, LS least squares, MMRM mixed-effect model for repeated measures, MMT manual muscle test, PROMIS Patient-Reported Outcomes Measurement Information System

Techniques: