Sostos Study Design: Assessing Transition to Ofatumumab from Other Disease-Modifying Therapies in RRMS after Elevation of Serum Neurofilament Light Levels

Background: Ongoing disease activity may not be clinically apparent and remain under the threshold of detection. As such, it is possible that patients who appear stable on their current DMT would benefit from transitioning to a higher efficacy agent. Additionally, although serum neurofilament light (NfL) holds promise as a potential biomarker for disease activity, the threshold at which an MS patient might benefit from a transition to a higher efficacy DMT is currently not defined.

Objectives: The SOSTOS study (NCT05090371) will assess whether RRMS patients without a relapse in the past year would benefit from a transition to ofatumumab (OMB) vs continuing on their current DMT. It also seeks to address whether pre-randomization serum NfL levels can inform prediction of benefit from a switch.

Methods: SOSTOS is a randomized, open-label, prospective, active comparator Phase 4 study. It will include RRMS patients, aged 18-45 years, EDSS 0-5.5, with no relapse within a year prior to randomization and currently receiving an injectable/oral DMT for ≥6 months prior to screening. Following screening, patients will enter a 6-month run-in period during which NfL levels will be obtained every 2 months. Subjects will then be randomized (1:1) to either switch to OMB or continue on their current DMT, and then will be followed for 15 months with a 4-week safety follow-up. Proportion of patients achieving NEDA-3 (relapse-free, 3-month clinical disability progression-free, MRI activity-free) in Months 3 to 15 will serve as the primary outcome. Key secondary objectives include achievement of NEDA-3 by baseline NfL levels, various clinical (NEDA, disability, relapse, MS functional composite-3) and conventional MRI metrics, patient-reported outcomes, brain volume loss, and safety/tolerability. Exploratory endpoints will include additional immunologic and biomarker assessments, digital assessment of patient biometrics, and treatment adherence/persistence.

Results: Study aims to enroll ~150 patients at up to 40 US and 10 Canadian centers. First study visit is expected to occur in Q1 2022, with study completion in 2025.

Conclusions: This study will provide important information on the merit of continuing on an oral/injectable DMT vs transitioning to OMB in RRMS patients without a relapse in the past year but with imaging/biomarker evidence of ongoing disease activity. It will also provide insights on the utility of NfL as a potential biomarker to identify patients who could clinically benefit from a switch to OMB.