HEALEY ALS Platform Trial
What is the HEALEY ALS Platform Trial?
This platform trial aims to accelerate the process of drug development and the path for effective treatment for ALS/MND by testing multiple drugs simultaneously and adaptively. This design has been seen to be successful in cancer trials. Compared to traditional drug development, the platform trial is estimated to find an effective therapy more quickly (average 3.4 vs. 8.5 years), with fewer total participants (average 880 vs. 1400), and fewer participants on placebo (average 220 vs. 700).
Participants will have an equal chance to be randomized to all regimens that are active at the time of screening. Once randomized to a regimen, participants will be randomized in a 3:1 ratio to either study drug or placebo. New regimens will be continuously added as new investigational products become available. The HEALEY ALS Platform Trial will enroll additional participants as each new regimen is available.
Current regimens active in the trial:
- Verdiperstat (Phase 3)
Regimens that have been stopped early due to lack of benefit:
- Zilucoplan (Phase 2)
What do the drugs do?
There is evidence to support that complement system (part of the immune system) activation plays a role in MND. This activation cause damage to tissues in the central nervous system. Zilucoplan is a inhibitor of part of this complement system, known as complement component 5. This prevents any tissue damage caused by the activation of the complement system.
One of the hallmarks of neurodegeneration in MND is the presence of large numbers of activated microglia. Microglia are the primary immune cells of the central nervous system. When these microglia are activated it results in the presence of myeloperoxidase (MPO) which is believed to increase oxidative stress and inflammation in the brain and spinal cord. Verdiperstat is an inhibitor of MPO and has the potential to reduce microglial activation.
CNM-Au8 is an oral liquid suspension of gold nanocrystals designed to improve nerve cells’ survival, function, and communication by supporting their energetic needs, while lowering oxidative stress. Preclinical studies showed that CNM-Au8 improved nerve cell survival and motor neuron function in rodent models of MND and other neurodegenerative diseases, such as multiple sclerosis, and Parkinson’s disease.
Pridopidine is a Sigma-1 receptor agonist, which means it activates the receptor causing a biological response. Sigma-1 receptor regulates key cellular pathways and is known to be impaired in neurodegeneration. The activation of the Sigma-1 receptor has been shown to exert neuroprotective effects in pre-clinical trials.
A characteristic sign of MND is clumps of proteins accumulating in motor neurone cells. One way that this clumps can be disposed of is through autophagy – which is the cells waste disposal mechanism. Trehalose can activate autophagy and potential help to treat MND. Pre-clinical trials have shown it to delay onset of disease and prolong survival.
This trial is recruiting in the US only.
Sept 2022 - Results from the Verdiperstat arm were announced. Unfortunately the primary endpoint was not met. You can read more in the press release.
March 2022 - Zilucoplan arm stopped early for futility. You can read more here
Feb 2022 - 5th arm SLS-005 (Trehalose) enrolled its first participants. You can read more here.
Jan 2022 - The trial completes enrollment for 4th arm Pridopipine. You can read more here.
Nov 2021 - The trial completes enrollment in the first 3 arms. You can read more here.
Want to find out more about the Healey ALS Platform Trial? Check out the resources below: