Table 5 Additional Endpoints

The following additional endpoints will undergo exploratory evaluation:

1. Number of patients who experienced sustained accumulation of disability (SAD) during the study period (Study period: From the day of treatment initiation until month 36 visit. SAD: for patients with a Baseline EDSS score of 0.0, SAD is defined as an increase of ≥1.5 points sustained over a 6-month consecutive period. For patients with a Baseline EDSS score of ≥1.0, SAD is defined as an increase of ≥1.0 point sustained over a 6-month consecutive period.)

2. Time to SAD

3. Time to sustained reduction in disability (SRD) based on EDSS scores (SRD: a ≥1 point decrease on the EDSS sustained for 6 consecutive months for patients with a baseline EDSS ≥2)

4. Absolute Number of relapses during the study period

5. Number or relapses which occurred during the study period and required corticosteroid therapy

6. Proportion of patients who are relapse free at year 3

7. Time to first relapse

8. Absolute and relative change from baseline in the following functional scores at each time point of assessment after treatment initiation (see Additional file 1: Assessment Schedule): EDSS, visual functional system score as part of the assessments for EDSS, MSFC and each MSFC component, FSMC and each subscore (mental and physical fatigue)

9. The proportion of patients who have worsened, remained stable, or improved as indicated by change from Baseline in EDSS scores at the end of the study

10. Change from baseline of the following HRQoL measures at each time point of assessment after treatment initiation (see Additional file 1: Assessment Schedule): FAMS, EQ-5D (total score, Physical Component summary Measure, Mental Component Summary Measure), SF-36

11. The proportion of patients who have worsened, remained stable, or improved as indicated by change from Baseline in MSFC scores at the end of the study

12. Absolute and relative change from baseline amplitudes [V] and latencies [s] of evoked potentials (VEP, SEP, MEP)

13. Percent change from baseline in magnetic resonance imaging (MRI)-T2 hyperintense lesion volume at each time point of assessment after treatment initiation (see Additional file 1: Assessment Schedule)

14. Number of new gadolinium-enhancing lesions on MRI-T1 in comparison to Baseline

15. Number of new or enlarging hyperintense lesions measured by T2-weighted MRI in comparison to Baseline at each time point of assessment (see Additional file 1: Assessment Schedule)

16. Absolute and relative change from baseline of IL-21 concentration in blood serum at indicated time-points of sampling

17. Absolute and relative change from baseline of following parameters assessed in CSF: cell counts, concentration of lactate, protein, and immunoglobulines (IgA, IgG, IgM)

18. Qualitative assessment of the change in presence of oligoclonal bands in CSF from baseline

19. Proportion of patients with no MS disease activity (i.e., deterioration in MRI related endpoints, relapse) at the end of the study