A Study of Monepantel in Individuals With Motor Neurone Disease
Status:
Not yet recruiting
Trial end date:
2022-11-01
Target enrollment:
Participant gender:
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.
Phase:
Phase 1
Details
Lead Sponsor:
PharmAust Ltd
Collaborators:
Calvary Health Care Bethlehem FightMND Macquarie University, Australia