Table 4.

Summary of select MS clinical trials prospectively evaluating biomarkers

	DELIVER-MS [102, 103] (NCT03535298)	TREAT-MS [104] (NCT03500328)	MS-ReBS [105] (NCT05204459)
Description	RRMS Interventional, observational, prospective, R, PG, SB n = 800 (400 randomized and 400 observational-estimated) Follow-up 36 months	RRMS Interventional, prospective, R, PG, SB n = 900 (estimated) Follow-up 75 months	MS, MS-related conditions, and others Observational, prospective n = 1000 (estimated) Follow-up 10 years
Intervention	1. Early HET group 2. Escalation group	1. Early HET group 2. Traditional DMT group	N/A
Primary	• BVL from baseline	• Time to sustained disability progression using EDSS-Plus	• Identify risk factors for disability progression (peripheral blood biomarkers, retinal structure, visual function, longitudinal MRIs)
Secondary	• BVL from month 6 • Multidimensional composite assessing progression (EDSS, T25FW, 9HPT, SDMT, LCLA) • MSIS-29 • Neuro-QoL	• PDDS • SDMT • MSFC (original and include LCLA) • Relapse recovery • MSIS-29 • Neuro-QoL • Employment/marital status • Safety (SAEs, AEs leading to DMT switch or change in medication administration)	• Effect of DMTs on disability risk • Identify factors associated with visual disability and optic neuropathy in MS and related disorders • Identify serum, genetic, and stem cell-derived biomarkers influencing disability risks
Tertiary/other	Biomarker discovery studies to evaluate predictors of longer-term disability and treatment response, with the goal to individualize treatment approaches in MS. Repository of biosamples collected includes frozen serum, whole plasma for DNA, and peripheral blood mononuclear cells	• Brain MRI (whole brain and normalized gray matter volumes, cortical thickness, subcortical gray matter compartment volumes, T2 lesion burden) • Number of relapses • New brain lesions on MRI • Retinal layer thicknesses by OCT • Number of new symptomatic interventions for MS-related symptoms • Biomarker discovery studies in parallel with DELIVER-MS	N/A

Presented data are correct as of July 30, 2023

9-HPT 9-Hole Peg Test, AE adverse event, BVL brain volume loss, COVID-19 coronavirus disease 2019, DMT disease-modifying therapy, EDSS Expanded Disability Status Scale, HET high-efficacy therapy, LCLA low-contrast letter acuity, MRI magnetic resonance imaging, MS multiple sclerosis, MSFC Multiple Sclerosis Functional Composite, MSIS-29 Multiple Sclerosis Impact Scale, N/A not applicable, OCT optical coherence tomography, PDDS Patient-Determined Disease Steps, PG parallel-group, R randomized, RRMS relapsing–remitting multiple sclerosis, SAE serious adverse event, SB single-blind, SDMT Symbol Digit Modalities Test, T25-FW Timed 25-Foot Walk