REFINE-MS: 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
Medical condition: Relapsing-remitting multiple sclerosis (RRMS) Medical condition in lay language: A long-term condition affecting the brain and spinal cord, where people experience episodes of new or worsening symptoms (relapses) followed by periods of recovery (remission). Therapeutic areas: Diseases [C] - Nervous System Diseases [C10]
Participants will be randomised in the REFINE-MS electronic data capture (eDC) system to receive ocrelizumab (ocrelizumab 600mg intravenous or 920mg subcutaneous). The dose frequency depends on the arm to which the participant is randomised. This trial includes 2 Stages (Stage 1 (divided into 1a and 1b) and Stage 2. In Stage 1a, 6-monthly vs 12-monthly frequencies will be tested, with 100 patients randomised across these two arms. Following this, the study will proceed directly to Stage 1b, in which 3 additional arms will open (9-monthly, 15-monthly and 18-monthly), meaning that participants can be randomised to all five arms. An interim analysis of 12 months of data in 90 of the original 100 participants randomised to 6 vs 12 months will be carried out to determine the design of Stage 2 of the trial. If 12-monthly is not inferior to 6-monthly in terms of proportion of patients with new T2 lesions after one year, patients will continue to be recruited to all five arms; if it is inferior, the trial will convert into a 2-arm non-inferiority trial of 9-monthly vs. 6-monthly frequencies. All participants will be followed up with for at least 2 years.
1. Adult participants aged ≥18 yrs 2. Diagnosis of RRMS, according to the 2017 or 2024 revised McDonald criteria 3. Received 4 or more 6-monthly cycles of ocrelizumab (IV or SC) according to NICE TA533 guidelines and the ocrelizumab summary of product characteristics (SPC), prior to randomisation 4. Expanded Disability Status Scale (EDSS) score between 0 and ≤6.5 inclusive at baseline 5. Participants who wish to remain on ocrelizumab 6. Written informed consent provided 7. At randomisation, participants must have a QC-approved Baseline MRI scan (per the MRI Guide), performed up to 6 weeks after the Screening/Baseline/M0 visit
1. Clinical relapse(s) within 12 months prior to randomisation 2. New MRI lesions prior to randomisation, assessed by the treating site through comparison of the trial baseline scan with the most recent preceding MRI performed at least 3 months earlier while the participant was receiving ocrelizumab 3. Co-treatment with other immunosuppressive medications 4. Any condition or circumstance that prevents the participant from undergoing regular MRI scanning 5. Pregnancy or intention to become pregnant during the study period