Journalartikel

Jahr der Veröffentlichung: 2022

Seiten: 1651-1662

Zeitschrift: Journal of Neurology

Bandnummer: 269

Heftnummer: 3

ISSN: 0340-5354

eISSN: 1432-1459

Open Access Status: Hybrid

DOI Link: https://doi.org/10.1007/s00415-021-10717-0

Verlag: Springer

Abstract: 
Objective 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.

Harvard-Zitierstil: Bremova-Ertl, T., Claassen, J., Foltan, T., Gascon-Bayarri, J., Gissen, P., Hahn, A., et al. (2022) Efficacy and safety of N-acetyl-l-leucine in Niemann-Pick disease type C, Journal of Neurology, 269(3), pp. 1651-1662. https://doi.org/10.1007/s00415-021-10717-0

APA-Zitierstil: Bremova-Ertl, T., Claassen, J., Foltan, T., Gascon-Bayarri, J., Gissen, P., Hahn, A., Hassan, A., Hennig, A., Jones, S., Kolnikova, M., Martakis, K., Raethjen, J., Ramaswami, U., Sharma, R., & Schneider, S. (2022). Efficacy and safety of N-acetyl-l-leucine in Niemann-Pick disease type C. Journal of Neurology. 269(3), 1651-1662. https://doi.org/10.1007/s00415-021-10717-0