VISIONARY-MS Top-line Results: A Phase 2, Randomized, Double-Blind, Parallel Group, Placebo-controlled Study to Assess the Safety and Efficacy of CNM-Au8, a Catalytically Active Gold Nanocrystal Suspension in Relapsing Multiple Sclerosis
Michael Barnett1, Heidi Beadnall3, Alexander Klistorner2, Robert Sergott4, Benjamin Greenberg 5, Austin Rynders 6, Karen Ho7, Jacob Evan7, Jeremy Evan6, Ryan McBride8, Alan Hartford6, Robert Glanzman6, Michael Hotchkin6
1Neurology, University of Sydney, 2University of Sydney, 3Neurology, Sydney Neurology, 4Wills Eye Hospital, 5Neurology, University of Texas Southwestern, 6Clene Nanomedicine Inc, 7Clene Nanomedicine, 8Instat

The objective of VISIONARY-MS was to assess the efficacy and safety of CNM-Au8 treatment on stable relapsing MS (RMS) patients on top of background disease modifying therapy (DMT).



CNM-Au8, an oral suspension of catalytically-active gold nanocrystals, supports brain energy metabolism resulting in neuroprotection and remyelination in preclinical models. 


VISIONARY-MS was a Phase 2, multicentre, randomized, double-blind, placebo-controlled study investigating CNM-Au8 versus placebo over 48 weeks in stable RMS patients. Enrolled subjects were randomized 1:1:1 to CNM-Au8 15mg/day, 30mg/day, or placebo. Key inclusion criteria: age 18-55 years, RMS diagnosis with disease duration <15 years, clinically stable over the prior 6-months, best corrected-low contrast letter acuity (BC-LCLA) using 2.5% low-contrast Sloan letter chart of 20/40 or worse in the affected eye, mean retinal nerve fibre layer thickness >70 mm in both eyes. The primary outcome was change in BC-LCLA score in the clinically most affected eye to week 48. Secondary outcomes assessed global neurological function by the modified MS Functional Composite (mMSFC) to week 48. Primary analyses were conducted in the modified intent to treat population, censoring invalid data from 1 of 11 clinical trial sites.  The study ended prematurely due to pandemic challenges with 73/150 planned. Statistical significance was prespecified at p=0.10, combining CNM-Au8 doses for these analyses. 


The primary BC-LCLA outcome LS-mean difference was 3.13 (95% CI: -0.08 to 6.33; p=0.056). 2 of 3 key secondary outcomes were significant: (i) LS-mean difference of mean standardized mMSFC score: 0.28 (95% CI: 0.04 to 0.52; p=0.0197); (ii) LS-mean difference of mMSFC average ranked sum score: 13.4 (95% CI: 2.8 to 23.9; p=0.0138). Exploratory endpoints: multi-focal VEP, MRI, and OCT metrics will be reported. Treatment emergent adverse events were transient, and mild-to-moderate in severity. 


These data provide evidence for improved neurological function in stable RMS patients treated with CNM-Au8 adjunctively to DMTs.