Task Order 8: RSA Home Spirometry and Open-Label Extension: Platform Trial for the Treatment of Amyotrophic Lateral Sclerosis

Grants and Contracts Details


Task Order 8: RSA Home Spirometry and Open-Label Extension : Platform Trial for the Treatment of Amyotrophic Lateral Sclerosis Regimen-Specific Appendix C For CNM-Au8 Rationale and RSA Design 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. The investigation of two doses of the study drug is based on counsel from the FDA recommending including a dose finding strategy in the study. The 30 mg and 60 mg doses of CNM-Au8 selected for the study achieve at least comparable AUC exposure in humans as those shown to demonstrate neuroprotection efficacy in nonclinical animals studies, and demonstrated minimal treatment emergent adverse events in the Phase 1 First-In-Human study in healthy volunteers. Allocation to Treatment Regimens Participants must first be screened under the Master Protocol before they are randomized to an RSA.
Effective start/end date9/4/202/2/24


  • Massachusetts General Hospital: $16,306.00


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