NCT04894240

A Study of Monepantel in Individuals With Motor Neurone Disease

Completed Phase 1 Last updated 21 December 2023

What this trial tests

Phase 1 trial testing Monepantel in Motor Neuron Disease in 12 participants. Completed in 29 November 2023.

Timeline

28 June 2022

Primary endpoint
29 November 2023

29 November 2023

Quick facts

Lead sponsor	Neurizon Therapeutics Limited
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	sequential
Masking	none
Primary purpose	treatment
Enrollment	12
Start date	28 June 2022
Primary completion	29 November 2023
Estimated completion	29 November 2023
Sites	2 locations across Australia

Drugs / interventions tested

• Monepantel — full drug profile →

Conditions studied

• Motor Neuron Disease — all drugs for Motor Neuron Disease →

Sponsor

Neurizon Therapeutics Limited

Who can join

Adults 18 to 75, any sex, with Motor Neuron Disease. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Amyotrophic lateral sclerosis/ Motor Neurone Disease (ALS/MND) is a rare and invariably fatal neurological disease. ALS/MND has a terribly high burden on patients, family and carers, and carries great socioeconomic burden. Current best treatment options are expensive and attempt to control disease progression and manage symptoms while offering no cure. Better treatments are wanting.

Monepantel is a well-known veterinary drug, registered as a livestock wormicide in 39 countries. The industry collaborator, PharmAust Ltd, has found that monepantel shows off-target activity, inhibiting a cellular signaling system controlled by mammalian target of rapamycin (mTOR). This stops cancer growth and reduces protein accumulation in diseased cells. PharmAust has already tested monepantel in humans and pet dogs in Phase I and II anti-cancer clinical trials, respectively, in Australia. Data from these trials show that monepantel treatment associates with an exceptionally high safety profile, mTOR signaling inhibition and anticancer activity.

Abnormal protein accumulation within motor neurons of the brain associates with the cause of ALS/MND. Inhibition of the mTOR signaling pathway slows disease progression in certain preclinical models of ALS/MND and is suggested to provide synergy with the ALS/MND standard-of-care drug, riluzole. An alternative mTOR inhibitor, rapamycin, is currently the subject of an ALS/MND clinical trial in humans investigating control of disease progression. Monepantel has a different structure to rapamycin and an apparently better safety profile.

This Phase I Clinical Trial hypothesis is that monepantel administration to individuals living with ALS/MND will safely reduce disease associated protein accumulation in motor neurons and provide therapeutic benefit. To test this hypothesis, the safety and tolerability of oral monepantel administration and markers of efficacy will be tested in individuals living with ALS/MND in a dose escalating Phase I/II Clinical Trial. To mitigate risk, only patients with sporadic and certain known familial types of ALS will be eligible. To further mitigate risk, the monepantel starting dose will be reduced a calculated five-fold compared to that already used in human cancer patients and already demonstrated to be safe and effective as an mTOR inhibitor. Dependent upon incremental outcomes, three higher doses may then be tested, each for minimally 28 days with a duration at the optimal dose of at least six months.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. Amyotrophic lateral sclerosis: a neurodegenerative disorder poised for successful therapeutic translation.
   Mead RJ, Shan N, Reiser HJ, Marshall F, et al · · 2023 · cited 323× · PMID 36543887 · DOI 10.1038/s41573-022-00612-2
2. New developments and opportunities in drugs being trialed for amyotrophic lateral sclerosis from 2020 to 2022.
   Jiang J, Wang Y, Deng M. · · 2022 · cited 48× · PMID 36518658 · DOI 10.3389/fphar.2022.1054006
3. Emerging Therapies and Novel Targets for TDP-43 Proteinopathy in ALS/FTD.
   Hayes LR, Kalab P. · · 2022 · cited 46× · PMID 35790708 · DOI 10.1007/s13311-022-01260-5
4. The role of autophagy in the pathogenesis and treatment of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
   Beckers J, Van Damme P. · · 2025 · cited 5× · PMID 40395983 · DOI 10.1080/27694127.2025.2474796
5. Genetic and Mechanistic Insights Inform Amyotrophic Lateral Sclerosis Treatment and Symptomatic Management: Current and Emerging Therapeutics and Clinical Trial Design Considerations.
   Quigley SE, Quigg KH, Goutman SA. · · 2025 · cited 2× · PMID 40897992 · DOI 10.1007/s40263-025-01217-0