A study to investigate the concordance of smartphone-based self-monitoring, imaging, and blood-based biomarkers with clinical disability in participants with multiple sclerosis

1. Digital outcomes measured using the Floodlight MS App at baseline and Years 1, 2, and 3
2. Upper limb function measured using the 9-hole Peg Test (9HPT) at baseline and years 1, 2, and 3
3. Lower limb function measured using the Timed 25-foot Walk Test (T25FWT) at baseline and years 1, 2, and 3
4. Neurocognitive function measured using the Symbol Digit Modalities Test (SDMT) at baseline and years 1, 2, and 3

1. Longitudinal digital outcomes measured weekly using the Floodlight MS App from baseline to Year 3
2. Neurologic impairment measured using the Expanded Disability Status Scale (EDSS) at baseline and years 1, 2, and 3
3. Visual function measured using the low-contrast visual acuity (LCVA) at baseline and years 1, 2, and 3. LCVA is scored as the total number of correct letters on a 2.5% contrast Sloan chart positioned at a 2-metre distance from the patient’s eyes.
4. Time to onset of Confirmed Disability Progression (CDP) for at least 48 weeks during the study period (time frame: 4 years). Disability progression is defined as an increase in the EDSS score of ≥1.5 points if the initial EDSS is 0, an increase of ≥1.0 point if the initial EDSS is >0 to ≤ 5.5, or an increase of ≥0.5 points if the initial EDSS is >5.5.
5. Time to onset of Confirmed Disability Improvement (CDI) for at least 48 weeks during the study period (time frame: 4 years). Disability improvement is defined as a decrease of ≥1.0 point if the initial EDSS is 2.0–5.5, or a decrease of ≥0.5 points if the initial EDSS is >5.5.
6. Time to onset of confirmed worsening of upper limb function for at least 48 weeks (time frame: 4 years). Worsening of upper limb function is defined as a 20% increase on the 9HPT.
7. Time to onset of confirmed improvement of upper limb function for at least 48 weeks (time frame: 4 years). Improvement of upper limb function is defined as a 20% decrease on the 9HPT.
8. Time to onset of confirmed worsening of lower limb function for at least 48 weeks (time frame: 4 years). Worsening of upper limb function is defined as a 20% increase on the T25FWT
9. Time to onset of confirmed improvement of lower limb function for at least 48 weeks (time frame: 4 years). Improvement of upper limb function is defined as a 20% decrease on the T25FWT.
10. Time to onset of confirmed worsening of neurocognitive function for at least 48 weeks (time frame: 4 years). Worsening of neurocognitive function is defined as a 4-point reduction on the SDMT.
11. Time to onset of confirmed improvement of neurocognitive function for at least 48 weeks (time frame: 4 years). Improvement of neurocognitive function is defined as a 4-point increase on the SDMT.
12. Time to onset of Progression Independent of Relapse Activity (PIRA) for at least 48 weeks (time frame: 4 years). PIRA is defined as EDSS worsening in the absence of Protocol Defined Relapse (PDR)
13. Time to onset of Composite Progression Independent of Relapse Activity (PIRA) for at least 48 weeks (time frame: 4 years). Composite PIRA is defined as a worsening on EDSS (an increase of ≥1.5 points if the initial EDSS is 0, an increase of ≥1.0 points if the initial EDSS is >0 to ≤ 5.5, or an increase of ≥0.5 points if the initial EDSS is >5.5), 9HPT (20% increase), T25FW (20% increase), SDMT (4-point decrease), or LCVA (7-point decrease) in the absence of PDR
14. Time to onset of Composite Disability Accumulation (CDA) for at least 48 weeks (time frame: 4 years). CDA is defined as worsening on the EDSS (an increase of ≥1.5 points if the initial EDSS is 0, an increase of ≥1.0 points if the initial EDSS is >0 to ≤ 5.5, or an increase of ≥0.5 points if the initial EDSS is >5.5), 9HPT (20% increase), T25FW (20% increase), SDMT (4-point decrease), or LCVA (7-point decrease)
15. Time to onset of Protocol-Defined Relapse (PDR) from baseline to year 3
16. Spasticity measured by the 88-item Multiple Sclerosis Spasticity Scale (MSSS-88; three subdomains of pain, spasms, and stiffness) at baseline and years 1, 2, and 3
17. Quality of life measured by EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L) at baseline and years 1, 2, and 3
18. Fatigue measured by the Neurological Fatigue Index (NFI)-MS at baseline and years 1, 2, and 3
19. Anxiety and depression measured by the Hospital Anxiety and Depression Scale (HADS) at baseline and years 1, 2, and 3
20. Physical and psychological impact of MS measured by the Multiple Sclerosis Impact Scale (29-item scale; MSIS-29) at baseline and years 1, 2, and 3
21. Quality of life measured by the World Health Organization Quality of Life: Abbreviated Version (WHOQOL-BREF) at baseline and years 1, 2, and 3
22. Subjective disability measured by the World Health Organization Disability Assessment Schedule-2 (WHODAS-2) at baseline and years 1, 2, and 3
23. Pain measured by the Neuropathic Pain Scale (NPS) at baseline and years 1, 2, and 3
24. Walking impairment measured by the Multiple Sclerosis Walking Scale (MSWS-12) at baseline and years 1, 2, and 3
25. Upper limb impairment measured by the ABILHAND-56 and Quality of Life in Neurologic Disorders (Neuro-QoL)-Upper Extremity (UE) at baseline and years 1, 2, and 3
26. Perceived benefit of FL MS measured using the In-App Post-Appointment Questionnaire at years 1, 2, and 3
27. FL MS usability measured using the health App Usability Questionnaire (MAUQ) at years 1, 2, and 3
28. FL MS adherence measured by the number of FL MS assessments completed from baseline to year 3
29. Percentage of participants with adverse events (AEs) from baseline up to year 3. AEs include adverse events related to usage of the FL MS App
30. Brain volume detected by brain magnetic resonance imaging (MRI) at baseline and at years 2 and 4
31. Thalamic volume detected by brain magnetic resonance imaging (MRI) at baseline and at years 2 and 4
32. Cervical cord area detected by cervical spinal cord magnetic resonance imaging (MRI) at baseline and at years 2 and 4
33. Rate of neuroaxonal injury measured using Serum Neurofilament Light Chain (NfL) concentration at baseline and years 1, 2, and 4