A Study of Monepantel in Individuals With Motor Neurone Disease
Condition: Motor Neuron Disease
MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis
Study type: Interventional
Phase: Phase 1

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.
    


Intervention name(s): Monepantel
Intervention type(s): Drug
Intervention description(s): Monepantel is provided to individuals living with ALS/MND as a white oval tablet to be administered once a day following meals
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Treatment