Bremova‐Ertl, TatianaClaassen, JensFoltan, TomasGascón-Bayarri, JordiGissen, PaulHahn, AndreasHassan, AnharHennig, AnitaJones, Simon A.Kolnikova, MiriamMartakis, KyriakosRaethjen, JanRamaswami, UmaSharma, ReenaSchneider, Susanne A.2021-09-102021-09-102021-08-131432-1459https://hdl.handle.net/2445/179931Objective: To investigate the safety and efficacy of N-acetyl-L-leucine (NALL) on symptoms, functioning, and quality of life in pediatric (≥ 6 years) and adult Niemann-Pick disease type C (NPC) patients. Methods: In this multi-national, open-label, rater-blinded Phase II study, patients were assessed during a baseline period, a 6-week treatment period (orally administered NALL 4 g/day in patients ≥ 13 years, weight-tiered doses for patients 6-12 years), and a 6-week post-treatment washout period. 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. Results: 33 subjects aged 7-64 years 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 = 2.52, 90% CI 0.25, 1.75, p = 0.029), as well as secondary endpoints. No treatment-related serious adverse events occurred. Conclusions: NALL demonstrated a statistically significant and clinical meaningfully improvement in symptoms, functioning, and quality of life in 6 weeks, 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. CLINICALTRIALS. Gov identifier: NCT03759639.12 p.application/pdfengcc by (c) Bremova‐Ertl, Tatiana et al, 2021http://creativecommons.org/licenses/by/3.0/es/Malaltia d'AlzheimerInfantsTerapèuticaAlzheimer's diseaseChildrenTherapeuticsinfo:eu-repo/semantics/article2021-09-10info:eu-repo/semantics/openAccess34387740