Brémovà-Ertl, TatianaTatianaBrémovà-ErtlClaassen, JensJensClaassenFoltan, TomasTomasFoltanGascon-Bayarri, JordiJordiGascon-BayarriGissen, PaulPaulGissenHahn, AndreasAndreasHahnHassan, AnharAnharHassanHennig, AnitaAnitaHennigJones, Simon ASimon AJonesKolnikova, MiriamMiriamKolnikovaMartakis, KyriakosKyriakosMartakisRaethjen, JanJanRaethjenRamaswami, UmaUmaRamaswamiSharma, ReenaReenaSharmaSchneider, Susanne ASusanne ASchneider2024-10-052024-10-052022-03https://boris-portal.unibe.ch/handle/20.500.12422/54191OBJECTIVE 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.enAcetyl-leucine Ataxia Lysosomal storage disorder Niemann–Pick disease type C Symptomatic therapy600 - Technology::610 - Medicine & healtharticle10.48350/1608113438774010.1007/s00415-021-10717-0