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; Schneider, Susanne A (2022). Efficacy and safety of N-acetyl-L-leucine in Niemann-Pick disease type C. Journal of neurology, 269(3), pp. 1651-1662. Springer 10.1007/s00415-021-10717-0

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology

UniBE Contributor:

Brémovà-Ertl, Tatiana

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1432-1459

Publisher:

Springer

Language:

English

Submitter:

Chantal Kottler

Date Deposited:

19 Nov 2021 15:32

Last Modified:

05 Dec 2022 15:54

Publisher DOI:

10.1007/s00415-021-10717-0

PubMed ID:

34387740

Uncontrolled Keywords:

Acetyl-leucine Ataxia Lysosomal storage disorder Niemann–Pick disease type C Symptomatic therapy

BORIS DOI:

10.48350/160811

URI:

https://boris.unibe.ch/id/eprint/160811

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