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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.

作者信息

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

机构信息

Friedrich-Baur-Institute, Department of Neurology, LMU University Clinic, Munich, Germany.

Reference Center for Neuromuscular Diseases and ALS, La Timone University Hospital, Aix-Marseille University, Marseille, France.

出版信息

J Neurol. 2025 Jan 7;272(1):103. doi: 10.1007/s00415-024-12843-x.


DOI:10.1007/s00415-024-12843-x
PMID:39775064
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11706903/
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 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.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/090a/11706903/595503021f02/415_2024_12843_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/090a/11706903/ca2994e37b06/415_2024_12843_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/090a/11706903/6bbe49eb589b/415_2024_12843_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/090a/11706903/595503021f02/415_2024_12843_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/090a/11706903/ca2994e37b06/415_2024_12843_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/090a/11706903/6bbe49eb589b/415_2024_12843_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/090a/11706903/595503021f02/415_2024_12843_Fig3_HTML.jpg

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