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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\u2009\u2265\u20093 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\u2009+\u2009mig and alg\u2009+\u2009pbo for change from baseline to week 52 in 6MWD was 11.7\u00a0m (95% confidence interval [CI]\u2009\u2212\u20091.0 to 24.4; <jats:italic>p<\/jats:italic>\u2009=\u20090.072). In the original published analyses, between-group difference using last observation carried forward was 13.6\u00a0m (95% CI\u2009\u2212\u20092.8 to 29.9; <jats:italic>p<\/jats:italic>\u2009=\u20090.071 [<jats:italic>p<\/jats:italic> value from separate non-parametric analysis of covariance]). Both statistical analysis approaches led to similar results and consistent conclusions, confirming the efficacy of cipa\u2009+\u2009mig for adults with LOPD. NCT03729362; trial start date: December 4, 2018.<\/jats:p>\n          <jats:p>Trial registration number<\/jats:p>","DOI":"10.1007\/s00415-024-12843-x","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T11:25:57Z","timestamp":1736249157000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"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"],"prefix":"10.1007","volume":"272","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2757-8131","authenticated-orcid":false,"given":"Benedikt","family":"Schoser","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahram","family":"Attarian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan","family":"Graham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fred","family":"Holdbrook","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitchell","family":"Goldman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordi","family":"D\u00edaz-Manera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"The ATB200-03 study group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,1,7]]},"reference":[{"key":"12843_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.2147\/odrr.S69109","volume":"7","author":"J Cabello","year":"2017","unstructured":"Cabello J, Marsden D (2017) Pompe disease: clinical perspectives. 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Benedikt Schoser has received unrestricted research grants from Amicus Therapeutics, Inc., Astellas, Roche Diagnostics, Marigold Foundation, and AMDA Foundation and speaker\u2019s honoraria from Amicus Therapeutics, Inc., Alexion, Kedrion, and Sanofi. He has participated as a scientific advisor for Amicus Therapeutics, Inc., Argenx, Astellas, Bayer, Maze, Pepgen, Sanofi, Spark, and Taysha. He declares no stocks or shares. Shahram Attarian has received consulting fees\/honoraria from Sanofi, Amicus Therapeutics, Inc., Argenx, and Alexion and grant support from Biogen. He has received payment for speaking from Sanofi, Pfizer, LFB, Argenx, Alexion, Janssen, Alnylam, Novartis, Biogen, and Roche. Ryan Graham\u00a0and Fred Holdbrook are employees of, and hold stock in, Amicus Therapeutics, Inc. Mitchell Goldman is a former employee of Amicus Therapeutics, Inc.\u00a0Jordi D\u00edaz-Manera has received consulting fees\/honoraria from Amicus, Astellas, Sarepta, Sanofi, Argenx, and Lupin and grant support from Sanofi, Spark, Sarepta, and Boehringer Ingelheim. He has received payment for speaking from Sanofi, Sarepta, and Lupin.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"This study was conducted in accordance with ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments, and in compliance with the United States Food and Drug Administration regulations in 21 Code of Federal Regulations 56, European Union Clinical Trials Regulation 536\/2014, and the International Council for Harmonisation Good Clinical Practice guidelines. For each study site, the clinical study protocol (and any amendments) and informed consent form were reviewed and approved by the appropriate independent ethics committee\/institutional review board.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"All patients provided signed informed consent before any study-related procedures were performed. In Japan, the patient\u2019s parental guardian (or legal representative) also had to sign the informed consent form for patients under 20\u00a0years of age.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent"}}],"article-number":"103"}}