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The primary Clinical Impression of Change in Severity (CI-CS) endpoint (based on a 7-point Likert scale) was assessed by blinded, centralized raters who compared randomized video pairs of each patient performing a pre-defined primary anchor test (8-Meter Walk Test or 9-Hole Peg Test) during each study periods. Secondary outcomes included cerebellar functional rating scales, clinical global impression, and quality of life assessments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      33 subjects aged 7\u201364\u00a0years with a confirmed diagnosis of NPC were enrolled. 32 patients were included in the primary modified intention-to-treat analysis. NALL met the CI-CS primary endpoint (mean difference 0.86, SD\u2009=\u20092.52, 90% CI 0.25, 1.75,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.029), as well as secondary endpoints. No treatment-related serious adverse events occurred.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>NALL demonstrated a statistically significant and clinical meaningfully improvement in symptoms, functioning, and quality of life in 6\u00a0weeks, the clinical effect of which was lost after the 6-week washout period. NALL was safe and well-tolerated, informing a favorable benefit-risk profile for the treatment of NPC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinicaltrials.gov identifier<\/jats:title>\n                    <jats:p>NCT03759639.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-021-10717-0","type":"journal-article","created":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T06:02:46Z","timestamp":1628834566000},"page":"1651-1662","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Efficacy and safety of N-acetyl-l-leucine in Niemann\u2013Pick disease type C"],"prefix":"10.1007","volume":"269","clinical-trial-number":[{"clinical-trial-number":"nct03759639","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7397-045X","authenticated-orcid":false,"given":"Tatiana","family":"Bremova-Ertl","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Claassen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Foltan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Gascon-Bayarri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Gissen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Hahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anhar","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Hennig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon A.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Kolnikova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyriakos","family":"Martakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Raethjen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uma","family":"Ramaswami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reena","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne A.","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,13]]},"reference":[{"key":"10717_CR1","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/s13023-018-0785-7","volume":"13","author":"T Geberhiwot","year":"2018","unstructured":"Geberhiwot T, Moro A, Dardis A et al (2018) Consensus clinical management guidelines for Niemann-Pick disease type C. 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JC and JR received fees for the blinded rater services from IntraBio. AH has received previous support from AbbVie and NCATS, and serves on the Editorial Board of Parkinsonism and Related Disorders. UR has received research grants from Amicus and Takeda, advisory board and lecture fee from Amicus, Sanofi Genzyme, and Takeda; all other authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"This study was conducted in accordance with the International Conference for Harmonisation (of Technical Requirements for Pharmaceuticals for Human Use)\u2014Good Clinical Practice Guideline, the General Data Protection Regulator, and the Declaration of Helsinki. Approval was obtained by the applicable responsible central research ethics committees \/ institutional review boards for each center (Ethics Committee of Ludwig Maximilian University of Munich (19-135), Slovakia: National Institute of Child Diseases Bratislava Ethics Committee (EudraCT 2018-004431-71), Bellvitge Hospital University Clinical Research Ethics Committee (AC001\/19), East Midlands\u2014Derby Research Ethics Committee (259038), Mayo Clinic Institutional Review Board (18-011974)).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Written informed consent was obtained for all study participants by the subject or, if applicable, their parent or legal representative.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. The study documents related to the study, and datasets generated and analyzed during the current study are not publicly available. No individual, de-identified participant data will be shared.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}