Optimizing rare disorder trials: a phase 1a/1b randomized study of KL1333 in adults with mitochondrial disease
Pizzamiglio, Chiara ; J. Stefanetti, Renae ; McFarland, Robert ; Thomas, Naomi ; Ransley, George ; Hugerth, Matilda ; Grönberg, Alvar ; Simon Serrano, Sonia LU ; Elmer, Eskil LU
and J. Hanna, Michael
, et al.
(2024)
In Brain
148(1).
p.39-46
- Abstract
- 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... (More) - 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/a3d5a9d0-f825-4f32-998f-543d40f99a9c
- author
- Pizzamiglio, Chiara
; J. Stefanetti, Renae
; McFarland, Robert
; Thomas, Naomi
; Ransley, George
; Hugerth, Matilda
; Grönberg, Alvar
; Simon Serrano, Sonia
LU
; Elmer, Eskil
LU
and J. Hanna, Michael
, et al. (More)
- Pizzamiglio, Chiara
; J. Stefanetti, Renae
; McFarland, Robert
; Thomas, Naomi
; Ransley, George
; Hugerth, Matilda
; Grönberg, Alvar
; Simon Serrano, Sonia
LU
; Elmer, Eskil
LU
; J. Hanna, Michael
; Hansson, Magnus
LU
; S. Gorman, Gráinne
and D. S. Pitceathly, Robert
(Less)
- organization
- publishing date
- 2024-12-09
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- primary mitochondrial disease, rare diseases, clinical trial, phase I trial, KL1333
- in
- Brain
- volume
- 148
- issue
- 1
- pages
- 39 - 46
- publisher
- Oxford University Press
- external identifiers
-
- pmid:39657714
- scopus:85214494844
- ISSN
- 1460-2156
- DOI
- 10.1093/brain/awae308
- project
- Development of treatment for mitochondrial disorders
- language
- English
- LU publication?
- yes
- id
- a3d5a9d0-f825-4f32-998f-543d40f99a9c
- date added to LUP
- 2025-01-10 12:46:41
- date last changed
- 2025-06-02 08:57:03
@article{a3d5a9d0-f825-4f32-998f-543d40f99a9c,
abstract = {{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.<br/><br/>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.<br/><br/>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 = {{Pizzamiglio, Chiara and J. Stefanetti, Renae and McFarland, Robert and Thomas, Naomi and Ransley, George and Hugerth, Matilda and Grönberg, Alvar and Simon Serrano, Sonia and Elmer, Eskil and J. Hanna, Michael and Hansson, Magnus and S. Gorman, Gráinne and D. S. Pitceathly, Robert}},
issn = {{1460-2156}},
keywords = {{primary mitochondrial disease; rare diseases; clinical trial; phase I trial; KL1333}},
language = {{eng}},
month = {{12}},
number = {{1}},
pages = {{39--46}},
publisher = {{Oxford University Press}},
series = {{Brain}},
title = {{Optimizing rare disorder trials: a phase 1a/1b randomized study of KL1333 in adults with mitochondrial disease}},
url = {{http://dx.doi.org/10.1093/brain/awae308}},
doi = {{10.1093/brain/awae308}},
volume = {{148}},
year = {{2024}},
}