REFINE-MS
Can people with relapsing-remitting MS who are stable on ocrelizumab take it less often and still keep their disease under control?
A randomised, rater-blind, phase 3 trial to determine the optimal dose frequency of ocrelizumab for patients with relapsing-remitting multiple sclerosis using a novel multi-arm multi-stage frequency-optimisation design
What is this study about?
Ocrelizumab is a highly effective treatment for relapsing-remitting multiple sclerosis (RRMS) that is administered by intravenous infusion or subcutaneous injection every six months. Although it substantially reduces relapses and new MRI lesions, long-term use is associated with increased infection risk, reduced vaccine efficacy, and high costs (approximately £19,160 per person per year). Evidence from clinical practice suggests that the beneficial effects of ocrelizumab may persist well beyond the standard six-month dosing interval, raising the possibility that less frequent dosing could maintain disease control while reducing side effects and NHS expenditure.
REFINE-MS is a multi-centre, randomised, rater-blind, open-label, phase 3 trial using a novel Multi-Arm Multi-Stage Response Over Continuous Interventions (MAMS-ROCI) design. It will enrol 540 adults with RRMS who have been stable on ocrelizumab for at least two years and will randomly assign them to continue treatment at dosing intervals of 6, 9, 12, 15, or 18 months. The trial operates in stages, beginning with a comparison of 6-monthly and 12-monthly dosing; an interim analysis after the first 90 participants have completed one year of follow-up will determine whether all five arms continue into the final stage. Participants will be followed for at least two years.
The primary objective is to identify the least frequent ocrelizumab dose that is non-inferior to the standard 6-monthly regimen, based on the proportion of participants free of new T2 lesions on brain MRI at two years. Secondary objectives include assessment of relapse rate, disability progression, adverse events, whole-brain atrophy, and quality of life. The trial also encompasses sub-studies addressing immunological biomarkers, MRI-based measures of chronic active lesions, digital mobility assessment using wearable sensors, and a study within a trial (SWAT) evaluating video-based participant information to support informed consent.
Type of study
Randomised trial
Contact details
Data Sharing
Data will be made available for sharing following publication of the primary outcome, in accordance with the InCTU controlled-access data-sharing policy. Researchers wishing to access REFINE-MS data should contact the Trial Management Group in the first instance. All data sharing will comply with the UK Data Protection Act 2018 and applicable information governance requirements. Biological samples collected as part of the mechanistic immunology sub-study will be destroyed at the end of the trial and will not be available for future research.
Who is funding the study?
National Institute for Health and Care Research (NIHR), grant reference 23/174. The trial is sponsored by University College London (UCL), with trial management delegated to the Innovative Clinical Trials Unit.
When is it taking place?
1 October 2025 - 30 September 2030
Where is it taking place?
United Kingdom. The trial is coordinated by the UCL Innovative Clinical Trials Unit (InCTU) in London. Recruitment will take place at multiple NHS neurology centres across the UK.
Who is included?
Adults aged 18 years or older with a confirmed diagnosis of relapsing-remitting MS (per the 2017 or 2024 revised McDonald criteria) who have received at least four 6-monthly cycles of ocrelizumab, have an Expanded Disability Status Scale (EDSS) score of 6.5 or below at baseline, have been free of clinical relapses for at least 12 months prior to randomisation, have no new MRI lesions on the baseline scan relative to the most recent preceding MRI performed while on ocrelizumab, and wish to continue ocrelizumab treatment. Participants must not be receiving concomitant immunosuppressive medications, must be able to undergo regular MRI scanning, and must not be pregnant or planning to become pregnant during the study period.