Efficacy and safety of N-acetyl-L-leucine in Niemann-Pick disease type C.
J Neurol
; 269(3): 1651-1662, 2022 Mar.
Article
in English
| MEDLINE | ID: covidwho-1733983
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.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Niemann-Pick Disease, Type C
Type of study:
Diagnostic study
/
Experimental Studies
/
Prognostic study
/
Randomized controlled trials
Limits:
Adolescent
/
Adult
/
Child
/
Humans
/
Middle aged
/
Young adult
Language:
English
Journal:
J Neurol
Year:
2022
Document Type:
Article
Affiliation country:
S00415-021-10717-0
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