Utilizing More Effective, Descriptive End Points in Multiple Sclerosis Trials: Michael Barnett, PhD, MBBS, FRACP

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"This is not a traditional trial. We are not looking at an anti-inflammatory therapy, we are looking at an adjunctive therapy in patients who are stable on an existing disease-modifying therapy."

Due to the heterogenous nature of the disease, it is a challenge to capture disease activity of multiple sclerosis (MS) in a reliable and valid way. In phase 3 trials in MS, the traditionally used primary clinical outcome measures are the Expanded Disability Status Scale (EDSS) and relapse rate, while other typical secondary end points include number or volume of T2 hyperintense lesions and gadolinium-enhancing T1 lesions on MRIs of the brain.

The phase 2 VISIONARY-MS study (NCT03536559), a placebo-controlled trial assessing CNM-Au8 (Clene Nanomedicine), an investigational agent for relapsing MS, has a unique design to it, in that it uses best corrected-low contrast letter acuity (BC-LCLA) in the clinically most affected eye as the primary end point. Comprised of individuals who have been clinically stable for 6 months prior, the study also assesses global function through the modified MS Functional Composite (mMSFC).

At the conclusion of the 48-week treatment period, investigators observed least square (LS) mean difference of 3.13 (95% CI, –0.08 to 6.33; P = .056) on the primary end point of BC-LCLA between CNM-treated patients and placebo. Lead investigator Michael Barnett, PhD, MBBS, FRACP, believes that testing the visual system is a great way of interrogating the capacity of a drug to remyelinate. Barnett, a senior academic at the University of Sydney, sat down in an interview to discuss the reasons for using these end points, and why they have such clinical utility in the MS field. Additionally, he spoke about why the significant benefits seen in already stable patients is so promising, and the uniqueness of this study.

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REFERENCE
1. Barnett M, Beadnall H, Klistorner A, et al. 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 nonocrystal suspension in relapsing multiple sclerosis. Presented at: 2023 AAN Annual Meeting; April 22-27; Boston, MA. Abstract 004273