Clinical trial NCT04894240: A Study of Monepantel in Individuals With Motor Neurone Disease
Official title: A Phase I Tolerability, Safety, Pharmacokinetics and Preliminary Efficacy Study of Oral Monepantel in Individuals With Motor Neurone Disease
Conditions: Motor Neuron Disease
Summary: 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.
Interventions:
description: Monepantel is provided to individuals living with ALS/MND as a white oval tablet to be administered once a day following meals
name: Monepantel
type: Drug
Study arms:
design_group_description: Monepantel tablets will be administered to participants in this arm daily for 28 days. Dose escalation will occur at the end of each 28 day period according to a modified Fibonacci sequence based upon recommendations from the safety management committee
design_group_title: Monepantel treatment arm
design_group_type: Experimental
Sponsor: Neurizon Therapeutics Ltd.
Collaborators: Macquarie University
Little Co. of Mary Health Care Ltd.
Cure For Mnd Foundation, Inc.
Drug name mappings:
name: Monepantel
lang: EN