Rationale: Ocrelizumab is widely and effectively used to treat relapsing multiple sclerosis (RMS). Phase II studies and data from large patient cohorts indicate that rituximab, another anti-CD20 monoclonal antibody, is probably equally effective and safe as ocrelizumab in the treatment of RMS. An advantage of rituximab is a considerably lower price. Therefore we will start a study aimed at demonstrating non-inferiority of rituximab compared to ocrelizumab in RMS. If non-inferiority of rituximab can be shown, important reductions in the cost of treatment of RMS will be possible, without loss of efficacy.
Objective: Evaluating the efficacy and safety of ritixumab compared to ocrelizumab in the treatmens of RMS.
Study design: Randomized double blind multi-centre non-inferiority study of rituximab compared to ocrelizumab in 200 patients with RMS. The trial duration will be 30 months
Study population: The study population consists of 200 adult RMS patiens with an indication to start anti-CD20 monoclonal antibody treatment.
Intervention: Patients will be randomized 1:1 into the standard group (ocrelizumab treatment) or the experimental group (rituximab treatment).
Main study parameters: To conclude non-inferiority of rituximab there will be one primary endpoint: the proportion of patients free of inflammatory disease activity (defined as: new or enlarged T2 lesions) between week 24 (M6) and week 96 (M24) of treatment in each arm. Secondary trial endpoints are presence and number of clinical relapses,T2 and contrast enhancing lesion volumes, brain volume and brain volume changes, disease progression (defined as clinically relevant change on any of the measures: EDSS, T25FW, 9HPT, SDMT), biochemical parameters such as lipidomics and neurofilament light (NfL), immunological parameters, safety as measured by the number of (serious) adverse events ((S)AE), quality of life (EQ-5D-L) and treatment satisfaction (TSQM) and patient reported measures of MS impact (MSIS-29) and well-being (questionnaire on physical complaints)
Nature and extent of the burden and risk: Patients included in this study will be treated and monitored by MRI, clinical tests and laboratory tests according to existing protocols and will not be exposed to extra or unknown risks. They will have extra annual questionnaires and larger blood samples at some time points. There is extensive experience with both rituximab and ocrelizumab as efficacious and safe treatments of RMS.
Men and women aged 18 years and older
A diagnosis of relapsing MS according to the 2017 revised diagnostic criteria
Indication to start treatment with anti-CD20 therapy according to the treating neurologist and the relevant label in the Netherlands for treatment of relapsing MS
Able to understand written and spoken Dutch or English
A known allergy or other intolerability to RTX, OCR, gadolinium-based MRI contrast agents, or corticosteroids.
A diagnosis of primary progressive MS according to the diagnostic criteria.
A diagnosis of not-active secondary progressive MS.
Chronic infectious diseases such as tuberculosis, VZV, hepatitis virus or HIV, as well as hepatitis B surface antigen positivity and/or hepatitis C PCR positivity verified at screening visit.
Parallel
Rituximab
DrugTreatment with rituximab
Proportion of patients free of inflammatory disease activity
Proportion of patients with no new or enlarged T2 lesions on brain MRI between month 6 and month 24
Presence and number of clinical relapses
Clinical relapses during treatment
Contrast enhancing lesions
Proportion of patients with no contrast enhancing lesions on brain MRI
Average number of T2 lesions on brain MRI
The average number of new/enlarged T2 lesions between baseline, month 6 and month 24 on brain MRI
Disability progression during follow-up
Disability progression measured on the Expanded Disability Status Scale (EDSS)
Anti-drug antibodies
Proportion of patients with anti-drug-antibodies during 30 months of treatment
Infusion reactions
Proportion of patients with immediate and delayed infusion reactions during 30 months of treatment
Infections
Proportion of patients with infections during 30 months of treatment
Malignancies
Proportion of patients with malignancies during 30 months of treatment
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Amsterdam UMC, location VUmc
Lead sponsor
Stichting Treatmeds
Collaborator
