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Lookup NU author(s): Dr Chiara Pizzamiglio, Dr Renae StefanettiORCiD, Professor Bobby McFarlandORCiD, Dr Naomi Thomas, Professor Michael Hanna, Professor Grainne Gorman, Dr Robert Pitceathly
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2024 The Author(s). Over the past two decades there has been increased interest in orphan drug development for rare diseases. However, hurdles to clinical trial design for these disorders remain. This phase 1a/1b study addressed several challenges, while evaluating the safety and tolerability of the novel oral molecule KL1333 in healthy volunteers and subjects with primary mitochondrial disease. KL1333 aims to normalize the NAD+:NADH ratio that is critical for ATP production. The trial incorporated innovative design elements with potential translatability to other rare diseases including patient involvement, adaptive design and exploratory objectives, all of which have subsequently informed the protocol of an ongoing phase 2, pivotal efficacy study of KL1333. Results indicate KL1333 is safe and well tolerated, with dose-dependent gastrointestinal side effects, and validate potential novel outcome measures in primary mitochondrial disease including the 30-s Sit to Stand, and the patient-reported fatigue scales. Importantly, the data from the trial support efficacy of KL1333 based on improvements in fatigue and functional strength and endurance. Furthermore, the study highlights the value in using phase 1 studies to capture data that helps optimize later phase efficacy trial design.
Author(s): Pizzamiglio C, Stefanetti RJ, McFarland R, Thomas N, Ransley G, Hugerth M, Gronberg A, Serrano SS, Elmer E, Hanna MG, Hansson MJ, Gorman GS, Pitceathly RDS
Publication type: Article
Publication status: Published
Journal: Brain
Year: 2025
Volume: 148
Issue: 1
Pages: 39-46
Print publication date: 01/01/2025
Online publication date: 09/12/2024
Acceptance date: 08/09/2024
Date deposited: 21/01/2025
ISSN (print): 0006-8950
ISSN (electronic): 1460-2156
Publisher: Oxford University Press
URL: https://doi.org/10.1093/brain/awae308
DOI: 10.1093/brain/awae308
Data Access Statement: The data supporting findings of this study are available from the corresponding author, upon reasonable request.
PubMed id: 39657714
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