Abstract Details

CNM-Au8, an oral suspension of clean-surfaced catalytically-active gold nanocrystals, enhances the energetic capacity of motor neurons via improved cellular energy metabolism resulting in significant neuroprotection and neurorepair in preclinical models. RESCUE-ALS was a phase 2, randomized, double-blind placebo-controlled clinical trial in early ALS. Treatment continuation was offered through an open-label extension (OLE). Long-term survival of all participants through 31-Dec-2021 (up to ~100 weeks from randomization) was evaluated.

To investigate the efficacy and safety the novel cellular energetic catalyst, CNM-Au8, as a disease-modifying treatment for amyotrophic lateral sclerosis (ALS).

ALS participants were randomized 1:1 to receive 30mg CNM-Au8 or placebo daily during the double-blind comparative period (36-weeks) followed by OLE treatment with CNM-Au8 (30mg/day). 45 participants were enrolled (n=23 active (CNM-Au8), n=22 matched placebo). Kaplan Meier survival analyses were conducted from randomization. Vital status and date of expiry was determined for all subjects, including those who withdrew or discontinued. Lost-to-follow-up (n=2) were censored at last contact. Sensitivity analyses compared observed survival versus predicted median survival derived from the published ENCALS model.

CNM-Au8 treatment demonstrated improved long-term survival versus placebo (deaths from randomization through 31-Dec-2021; CNM-Au8, n=3; placebo, n=8; HR: 0.342, 95% CI: 0.11, 1.12; p=0.096). Sensitivity analyses showed fewer CNM-Au8 deaths compared to ENCALS prediction (3 vs. 10 events; HR: 0.297, 95% CI: 0.10, 0.89; p=0.05). Furthermore, the subset of placebo participants who transitioned to CNM-Au8 in the OLE (n=16) also demonstrated improved survival versus ENCALS predicted (2 vs. 7 events; HR: 0.21, 95% CI: 0.056, 0.78; p=0.03).

These results demonstrate improved long-term survival in participants originally randomized to CNM-Au8 treatment. Increased risk of death was observed in participants who (i) were originally randomized to placebo, or (ii) who did not transition into the OLE. These results support CNM-Au8 treatment as effective for ALS disease modification.