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
• Publication Date: 2025-01-07T11:25:57Z
• Authors: Benedikt Schoser; Shahram Attarian; Ryan Graham; Fred Holdbrook; Mitchell Goldman; Jordi Díaz-Manera
• Keywords: Post-hoc analysis; Clinical endpoint; Post hoc

Abstract PROPEL (ATB200-03; NCT03729362) compared the efficacy and safety of cipaglucosidase alfa plus miglustat (cipa + mig), a two-component therapy for late-onset Pompe disease (LOPD), versus alglucosidase placebo (alg pbo). The primary endpoint was change in 6-min walk distance (6MWD) from baseline to week 52. During PROPEL, COVID-19 interrupted some planned study visits assessment windows, leading delayed visits, make-up assessments patients who missed ≥ 3 successive infusions before at weeks 38 52, advanced (end-of-study/early-termination visits). These were remapped respective visits. To evaluate if remapping may have overestimated treatment effects, we conducted post hoc analyses using mixed-effect model repeated measures based on actual time points assessments. In this analysis, estimated mean difference between cipa mig alg pbo 52 6MWD 11.7 m (95% confidence interval [CI] − 1.0 24.4; p = 0.072). original published analyses, between-group last observation carried forward 13.6 CI 2.8 29.9; 0.071 [ value separate non-parametric analysis covariance]). Both statistical approaches led similar results consistent conclusions, confirming adults with LOPD. NCT03729362; trial start date: December 4, 2018. Trial registration number