Task Order 3: Regimen-Specific Appendix (RSA) B to Mast Protocol Verdiperstat: Double-Blind Phase

The HEALEY ALS Platform Trial is a perpetual multi-center, multi-regimen clinical trial evaluating the safety and efficacy of investigational products for the treatment of ALS. The trial is designed as a perpetual platform trial. This means that there is a single Master Protocol dictating the conduct of the trial. CNM-Au8 is a suspension of clean-surfaced, faceted gold nanocrystals whose catalytic activity independently impacts energetic, metabolic, and redox pathways, resulting in significant neuroprotection from oxidative and excitotoxic insults. CNM-Au8 is a nanocatalyst that is administered orally, penetrates the blood brain barrier, and has a unique mechanism of action involving: (1) the catalytic production of nicotinamide adenine dinucleotide (NAD), a key co-factor in the ATP-generating pathways of all cells, (2) catalytic anti-oxidative activity resulting in cellular protection from oxidative stress, and (3) catalytic stimulation of the pentose phosphate pathway, influencing both anti-oxidative as well as anabolic processes. Importantly, CNM-Au8 demonstrated significant neuroprotection of healthy human motor neurons from cell death induced by toxic ALS-participant derived astrocytes, and of primary rat motor neurons from glutamatergic excitotoxicity. Oral delivery of CNM-Au8 to a mouse model of ALS resulted in the recovery of functional behaviors and significant extension of lifespan. Given the involvement of cellular bioenergetic failure in the pathogenesis of ALS, the development of a disease modifying therapeutic that addresses the energetic dysregulation underlying the progressive accumulation of oxidative stress and dysregulated RNA processing is a rational therapeutic strategy. This clinical protocol will test CNM-Au8 at doses of 30 mg and 60 mg versus placebo in a randomized, double-blind manner, to determine if CNM-Au8 can demonstrate sufficient efficacy and safety on accepted clinical and paraclinical outcomes for the treatment of ALS.