Table 2.

Secondary objectives of the MESEMS project

Aim	Measures
To compare the number of active MRI lesions in the placebo vs active treatment periods in both groups	Number of GEL counted over weeks 28, 36, and 48 (cross-over re-treatment) compared with the number of GEL counted over 4, 12, and 24 weeks (placebo vs active treatment periods) within each group
To evaluate efficacy of MSC in reducing combined MRI activity and volume of black holes (BH) in both treatment groups at 24 weeks	Combined unique MRI activity (number of new or enlarging T2w, or enhancing or re-enhancing lesions) and volume of GEL over 4, 12, and 24 weeks compared between treatment groups. Volume of BH over 24 weeks compared between treatment groups
To compare combined MRI activity and volume of BH in the placebo vs active treatment periods in both groups	Combined unique MRI activity and volume of GEL over weeks 28, 36, and 48 (cross-over re-treatment) compared with the same outcomes over 4, 12, and 24 weeks (placebo vs active treatment periods) within each group. Volume of BH over week 48 (cross-over re-treatment) compared with the same outcome over week 24 week (placebo vs active treatment periods) within each group
To evaluate efficacy of MSC in reducing the volume of T2 lesions in both treatment groups at 24 weeks	Volume of T2w lesions over 24 weeks compared between treatment groups
To compare the volume of T2 lesions in the placebo vs active treatment periods in both groups	Volume of T2w lesions over week 48 (cross-over re-treatment) compared with the same outcome over week 24 week (placebo vs active treatment periods) within each group
To evaluate efficacy of MSC in reducing relapses at 24 weeks and to compare the number of relapses in the placebo vs active treatment periods in both groups	Number of relapses in MSC treatment group vs placebo group in the first 24 weeks and after cross-over re-treatment in the two groups (see below for definition of relapse)
To evaluate efficacy of MSC in reducing the time to sustained progression of disability and increasing the number of progression-free patients at 24 weeks and to compare the time to sustained progression of disability and the proportion of progression-free patients in the placebo vs active treatment periods in both groups*	Time to sustained progression of disability and proportion of progression-free patients compared between treatment groups during the first 24 weeks and after cross-over re-treatment in the two groups
To evaluate efficacy of MSC in increasing the number of progression-free patients at 24 weeks and to compare the proportion of disease-free patients in the placebo vs active treatment periods in both groups§	Proportion of disease-free patients compared between treatment groups during the first 24 weeks and after cross-over re-treatment in the two groups
To evaluate the efficacy of MSC treatment in clinical scores such a Multiple Sclerosis Functional Composite (MSFC) score and Symbol Digit Modalities Test (SDMT) score	Changes in MSFC and SDMT scores in the MSC treated group vs placebo group during the first 24 weeks and after cross-over re-treatment in the two groups

*Sustained progression of disease is defined as any 6-month sustained increase in EDSS: for baseline EDSS < 5.5, any 1-point EDSS increase; for baseline EDSS ≥ 5.5, any 0.5-point EDSS increase

^§Disease-free: patients without relapses, with no evidence of sustained progression of disability and new MRI activity