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

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.

• Authors: Tatiana Bremova-Ertl, Jens Claassen, Tomas Foltan, Jordi Gascon-Bayarri, Paul Gissen, Andreas Hahn, Anhar Hassan, Anita Hennig, Simon A Jones, Miriam Kolnikova, Kyriakos Martakis, Jan Raethjen, Uma Ramaswami, Reena Sharma, Susanne A Schneider
• Journal: Journal of neurology (J Neurol) Vol. 269 Issue 3 Pg. 1651-1662 (Mar 2022) ISSN: 1432-1459 [Electronic] Germany
• PMID: 34387740 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial)
• Copyright: © 2021. The Author(s).

Chemical References

• Leucine
• acetylleucine

Topics

• Adolescent
• Adult
• Child
• Double-Blind Method
• Humans
• Leucine (analogs & derivatives, therapeutic use)
• Middle Aged
• Niemann-Pick Disease, Type C (diagnosis, drug therapy)
• Quality of Life
• Treatment Outcome
• Young Adult