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 (PL5.005)

<h3>Objective:</h3> 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). <h3>Background:</h3> CNM-Au8, an oral suspension of catalytically-active gold nanocrystals, supports brain energy metabolism resulting in neuroprotection and remyelination in preclinical models. <h3>Design/Methods:</h3> 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. <h3>Results:</h3> 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. <h3>Conclusions:</h3> These data provide evidence for improved neurological function in stable RMS patients treated with CNM-Au8 adjunctively to DMTs. <b>Disclosure:</b> Michael Barnett has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sydney Neuroimaging Analysis Centre. An immediate family member of Michael Barnett has received stock or an ownership interest from RxMx. The institution of Michael Barnett has received research support from Genzyme Sanofi. The institution of Michael Barnett has received research support from Biogen. The institution of Michael Barnett has received research support from Novartis. Dr. Beadnall has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Beadnall has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Beadnall has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. The institution of Dr. Beadnall has received research support from MSBase Foundation. Alexander Klistorner has nothing to disclose. Dr. Sergott has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Sergott has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon Therapeutics. Dr. Sergott has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Greenberg has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Horizon. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi/Genzyme. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunovant. Dr. Greenberg has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech/ROche. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Signant-2022. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for IQVIA. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sandoz. Dr. Greenberg has received personal compensation in the range of $0-$499 for serving as a Consultant for Intervenn. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer. Dr. Greenberg has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for TWI. Dr. Greenberg has stock in GenrAb. The institution of Dr. Greenberg has received research support from CLENE Nanomedicine. The institution of Dr. Greenberg has received research support from Anokion. The institution of Dr. Greenberg has received research support from Regeneron. Dr. Greenberg has received intellectual property interests from a discovery or technology relating to health care. Dr. Greenberg has received publishing royalties from a publication relating to health care. Dr. Greenberg has a non-compensated relationship as a Scientific Board with Siegel Rare Neuroimmune Association that is relevant to AAN interests or activities. Mr. Rynders has received personal compensation for serving as an employee of Clene Nanomedicine. An immediate family member of Mr. Rynders has received personal compensation for serving as an employee of Recursion Pharmaceuticals. Mr. Rynders has stock in Clene Nanomedicine. An immediate family member of Mr. Rynders has stock in Recursion Pharmaceuticals. Dr. Ho has received personal compensation for serving as an employee of Clene Nanomedicine. Dr. Ho has stock in Clene Nanomedicine. Mr. Evan has received personal compensation for serving as an employee of Clene Nanomedicine. Mr. Evan has stock in Clene Nanomedicine . Mr. Evan has received personal compensation for serving as an employee of Clene Nanomedicine. An immediate family member of Mr. Evan has received personal compensation for serving as an employee of Clene Nanomedicine. Mr. Evan has stock in Clene Nanomedicine Inc. Mr. McBride has nothing to disclose. Mr. Hartford has received personal compensation for serving as an employee of Clene Nanomedicine. Mr. Hartford has received personal compensation for serving as an employee of Takeda. Mr. Hartford has stock in AbbVie. Mr. Hartford has stock in Takeda. Dr. Glanzman has received personal compensation for serving as an employee of Clene Nanomedicine Inc. Dr. Glanzman has stock in Clene Nanomedicine Inc . Mr. Hotchkin has received personal compensation for serving as an employee of Clene Nanomedicine, Inc. Mr. Hotchkin has stock in Clene Nanomedicine, Inc.