Efficacy and safety of N-acetyl-l-leucine in Niemann-Pick disease type C

Bremova-Ertl, Tatiana; Claassen, Jens; Foltan, Tomas; Gascon-Bayarri, Jordi; Gissen, Paul; Hahn, Andreas; Hassan, Anhar; Hennig, Anita; Jones, Simon A.; Kolnikova, Miriam; Martakis, Kyriakos; Raethjen, Jan; Ramaswami, Uma; Sharma, Reena und Schneider, Susanne A. (2021): Efficacy and safety of N-acetyl-l-leucine in Niemann-Pick disease type C. In: Journal of Neurology, Bd. 269, Nr. 3: S. 1651-1662

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0340-5354
• Sprache: Englisch