Abstract
Objective CNM-Au8, an oral suspension of clean-surfaced, catalytically-active gold nanocrystals, improves central nervous system energy metabolism, resulting in neuroprotection and neurorepair in multiple preclinical models. RESCUE-ALS was a phase 2, randomized, double-blind placebo-controlled clinical trial whose objective was to evaluate the efficacy and safety of CNM-Au8 as a disease-modifying treatment for amyotrophic lateral sclerosis (ALS).
Methods ALS participants were randomized 1:1 to receive CNM-Au8 30mg/day or placebo for 36 weeks followed by open-label extension (OLE) with CNM-Au8 (30mg/day). 45 participants were enrolled (n=23 active; n=22 placebo) in the double-blind portion. 36 of 40 eligible entered the OLE. Vital status and date of expiry was determined for all subjects, including those who withdrew or discontinued from the study. Lost-to-follow-up (n=2) were censored at last contact. Kaplan Meier survival analyses were conducted from randomization comparing observed survival to median predicted survival derived from the validated ENCALS model. All observations censored as of 1-Feb-2022.
Results Amongst originally randomized placebo patients who did not enter the OLE, there were 6 deaths vs. 5 predicted. Amongst OLE participants treated with CNM-Au8 30mg (n=36), long-term observed survival was greater than ENCALS predicted median survival (observed, n=6; predicted, n=16; log-rank HR: 0.32, 95% CI: 0.13 to 0.72; p=0.009).
Conclusion Long-term CNM-Au8 treatment suggests improved survival compared to median predicted survival.
