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<p>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 alfa plus 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 and assessment windows, leading to delayed visits, make-up assessments for patients who missed ≥ 3 successive infusions before planned assessments at weeks 38 and 52, and some advanced visits (end-of-study/early-termination visits). These were remapped to the respective planned visits. To evaluate if remapping may have overestimated treatment effects, we conducted post hoc analyses using a mixed-effect model for repeated measures based on actual time points of assessments. In this post hoc analysis, estimated mean treatment difference between cipa + mig and alg + pbo for change from baseline to week 52 in 6MWD was 11.7&#xa0;m (95% confidence interval [CI] − 1.0 to 24.4; <i>p</i> = 0.072). In the original published analyses, between-group difference using last observation carried forward was 13.6&#xa0;m (95% CI − 2.8 to 29.9; <i>p</i> = 0.071 [<i>p</i> value from separate non-parametric analysis of covariance]). Both statistical analysis approaches led to similar results and consistent conclusions, confirming the efficacy of cipa + mig for adults with LOPD. NCT03729362; trial start date: December 4, 2018.</p><p>Trial registration number</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月7日

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  • Benedikt Schoser,
  • Shahram Attarian,
  • Ryan Graham,
  • Fred Holdbrook,
  • Mitchell Goldman,
  • Jordi Díaz-Manera

摘要

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

Trial registration number