RESCUE-ALS Trial Results: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of CNM-Au8 to Slow Disease Progression in ALS


Clinical Trials

Poster Number: 34


Robert Glanzman, MD, FAAN, Clene Nanomedicine Inc, Parvathi Menon, PhD, FRACP, Concord Repatriation General Hospital, University of Sydney, Australia, William Huynh, PhD, FRACP, Brain and Mind Centre, University of Sydney, Australia, Colin Mahoney, PhD, MB, MRCPI, Brain and Mind Centre, University of Sydney, Australia, Karen Ho, PhD, Clene Nanomedicine, Inc., Austin Rynders, RN, Clene Nanomedicine, Inc., Jacob Evan, Clene Nanomedicine, Inc., Jeremy Evan, PA-C, Clene Nanomedicine, Inc., Michael T. Hotchkin, Clene Nanomedicine, Inc., Matthew C. Kiernan, PhD, DSc, MBBS, FRACP, FAHMS, Brain and Mind Centre, University of Sydney, Australia, Steve Vucic, PhD, DSc, FRACP, FAHMS, Concord Repatriation General Hospital, University of Sydney, Australia

RESCUE-ALS was a Phase 2 randomized, double-blind, placebo-controlled study of CNM-Au8 as treatment for early sporadic ALS. CNM-Au8 is a suspension of clean-surfaced, catalytically active gold nanocrystals shown to enhance neuronal metabolic energy, reduce oxidative stress, and improve protein homeostasis.

Participants were randomized 1:1 to receive 30mg CNM-Au8 or placebo daily for 36 weeks. The primary endpoint was the percent change in the summated motor unit index (MUNIX) scores for the abductor digit minimi, abductor pollicis brevis, tibialis anterior, and biceps brachii. Secondary and exploratory endpoints included respiratory function, ALS disease progression, and quality of life.

45 participants (73% limb onset, 27% bulbar) were enrolled. Baseline characteristics of the intent-to-treat (ITT) population include [mean (SD)], age: 59.1 (12.3), months from symptom onset: 15.8 (9.3), FVC % predicted: 81.5 (16.7); ALSFRS-R: 38.7 (6.0); ENCALS risk score: –4.4 (1.8). The primary endpoint was not significant (least-squares [LS] mean difference: 7.7% (95% CI: –11.9% to 27.3%; p=0.430), which was driven by limited decline in bulbar-onset placebo participants (8% decrease in LS mean at week 36). In pre-specified analyses of limb-onset participants, there was a strong trend for reducing MUNIX decline (LS mean difference 20.9%, 95% CI: 2.2% to 44.0%; p=0.074). Notably, a significant reduction in ALS disease progression (defined as occurrence of death, tracheostomy, non-invasive ventilatory support, or gastrostomy tube placement) was evident in CNM-Au8 treated participants at week 36 (37% absolute risk reduction, p=0.013), and the proportion experiencing ? 6-point decline in ALSFRS-R was significantly reduced in the CNM-Au8 treated patients (p=0.035, chi-square test). CNM-Au8 treated participants demonstrated quality of life improvement (ALSSQOL-SF LS mean difference: 0.9; 95% CI: 0.2, 1.6; p=0.018). There were no significant adverse effects.

RESCUE-ALS has established safety and suggested efficacy of CNM-Au8 in ALS. A larger study is underway to confirm efficacy of CNM-Au8 in ALS.