A Phase 3 interventional study of Rituximab and Ocrelizumab in Relapsing Remitting Multiple Sclerosis, sponsored by Haukeland University Hospital. Active, not recruiting at 12 sites in 2 countries. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2025-06-27.
Sponsored by Haukeland University Hospital · Phase 3, Interventional, and Treatment
This is a multicenter non-inferiority study, designed to establish non-inferiority of the study treatment rituximab compared with the comparator ocrelizumab for consecutively included patients (male or female) with active relapsing-remitting multiple sclerosis aged 18-60 years.
The objective of the study is to demonstrate if rituximab is non-inferior to ocrelizumab with regards to efficacy and safety in treatment naïve RRMS patients, diagnosed within the last 12 months.
To test this hypothesis, the investigators aim to perform a 30-months (24 + 6 months) prospective randomized double blinded multicenter non-inferiority study to compare rituximab to ocrelizumab in RRMS.
MS disease activity as measured by brain MRI is more sensitive as compared to clinical disease activity as measured by number of relapses or disability progression. New or enlarging MRI T2 lesions is regarded an acceptable marker of disease activity, and is routinely used in clinical practice by annual examinations (Thompson, Baranzini et al. 2018) (Thompson, Banwell et al. 2018). The investigators will therefore use the proportion of patients with no new or enlarging T2-weighted brain MRI lesions from month 6 to month 24 as the primary endpoint of this study.
Secondary objectives are included to further evaluate potential the difference or similarities in effectiveness between the treatments (disability progression, relapse rate, T25FW, 9-HPT, SDMT), to evaluate the difference in safety issues (most notably hematological complications, infections, malignancies, infusion reactions and other serious adverse events) and to evaluate the difference in patient reported outcomes by evaluation of working status, fatigue, anxiety and depressive symptoms, quality of life and treatment satisfaction (EQ-5D, MSIS-29, FSMC, and SDMT). The exploratory outcomes are included to evaluate specific blood samples and plasma biomarkers for treatment response (sNFL and CD19+ cell counts) and side effects (hypogammaglobulinemia and neutropenia) of the two treatments, differences in vaccination status (pneumococcus and/or influenza) and to determine the predictive value of BICAMS for the individual patient.
602 studies on the registry are indexed under Multiple Sclerosis, Relapsing-Remitting; 80 are open to participants now.
This study's enrollment of 214 is above the median of 72 across 429 interventional studies indexed under Multiple Sclerosis, Relapsing-Remitting.
Browse Multiple Sclerosis, Relapsing-Remitting studies →Haukeland University Hospital is the lead sponsor of 276 studies on the registry; 61 are open to participants now.
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Exclusion Criteria:
Rituximab will be given as infusion at week 0, week 26, week 52, week 78, and week 104 unless there is a reason for schedule modifications (see Section 6.3). Each infusion is given over approximately 4 hours and follow local guidelines for infusion. Initial dose; 1000 mg Subsequent doses; 500 mg
Drug: Rituximab
Ocrelizumab will be given as infusion at week 0, week 26, week 52, week 78, and week 104 unless there is a reason for schedule modifications (see Section 6.3). Each infusion is given over approximately 4 hours and follow local guidelines for infusion. Initial and subsequent doses; 600 mg
Drug: Ocrelizumab
A prospective randomized double blinded multicenter non-inferiority study designed to establish non-inferiority of the study treatment rituximab compared with the comparator ocrelizumab for consecutively included patients (male or female) with active relapsing-remitting multiple sclerosis aged 18-60 years. Active substance is biosimilar rituximab iv infusion and comparator is ocrelizumab (Ocrevus ®) iv infusion. Both treatments are given as infusion at month 0, month 6, month 12, month 18 and month 24. Randomization rituximab: ocrelizumab is 3:2. The primary end-point is proportion of patients with no new or enlarging T2-weighted brain MRI lesions between re-baselining at month 6 and month 24.
Also known as: mabthera
A prospective randomized double blinded multicenter non-inferiority study designed to establish non-inferiority of the study treatment rituximab compared with the comparator ocrelizumab for consecutively included patients (male or female) with active relapsing-remitting multiple sclerosis aged 18-60 years. Active substance is biosimilar rituximab iv infusion and comparator is ocrelizumab (Ocrevus ®) iv infusion. Both treatments are given as infusion at month 0, month 6, month 12, month 18 and month 24. Randomization rituximab: ocrelizumab is 3:2. The primary end-point is proportion of patients with no new or enlarging T2-weighted brain MRI lesions between re-baselining at month 6 and month 24.
Also known as: ocrevus
Proportion without new MRI activity
Proportion of patients with no new or enlarging T2-weighted brain MRI lesions
Time frame: From month 6 (re-baseline) to month 24
Proportion of patients with 6-months confirmed disability progression (6M-CDP)
Proportion of patients with 6-months confirmed disability progression (6M-CDP) as measured by the Expanded disability status scale (EDSS) (Kurtzke 1983) from baseline to month 24. CDP-EDSS defined as an increase of one point in the EDSS score confirmed after 6 months, with an absence of relapse at the time of assessment.
Time frame: From baseline to month 24
Proportion of patients with 6-months confirmed disability improvement (6M-CDI)
Proportion of patients with 6-months confirmed disability improvement (6M-CDI) as measured by the Expanded disability status scale (EDSS) (Kurtzke 1983) from baseline to month 24. CDI-EDSS is defined as a decrease of one point in the EDSS score, confirmed after 6 months, with an absence of relapse at the time of assessment.
Time frame: From baseline to month 24
Annual relapse rate
The annual relapse rate from baseline to month 24
Time frame: From baseline to month 24
Proportion of patients without relapses
Proportion of patients without relapses from baseline to month 24
Time frame: From baseline to month 24
Proportion of patients with 6M-CDP in T25FW
Proportion of patients with 6M-CDP in T25FW (Cutter, Baier et al. 1999) from baseline to month 24. 6M-CDP in T25FW is defined as patients experiencing an increase of ≥20% from baseline which is confirmed after 6 months (Bosma, Kragt et al. 2010, Motl, Cohen et al. 2017).
Time frame: From baseline to month 24
Proportion of patients with 6M-CDP in 9-HPT
Proportion of patients with 6M-CDP in 9-HPT (Cutter, Baier et al. 1999) 8.2.6) from baseline to month 24. 6M-CDP in 9HPT is defined as patients experiencing an increase of ≥20% from baseline which is confirmed after 6 months (Bosma, Kragt et al. 2010, Feys, Lamers et al. 2017).
Time frame: From baseline to month 24
Proportion of patients with 6M-CDP in SDMT
Proportion of patients with 6M-CDP in SDMT from baseline to month 24. SDMT is defined as patients experiencing a reduction of 15% from baseline which is confirmed after 6 months (Strober, DeLuca et al. 2019, Marstrand, Osterberg et al. 2020)
Time frame: From baseline to month 24
Proportion of patients with no new or enlarging T2-weighted brain MRI lesions
Proportion of patients with no new or enlarging T2-weighted brain MRI lesions from baseline to month 6, and from baseline to month 24
Time frame: From baseline to month 6, and from baseline to month 24
Proportion of patients without new gadolinium enhancing T1-weighted brain MRI lesions
Proportion of patients without new gadolinium enhancing T1-weighted brain MRI lesions at month 6, month 12 and month 24
Time frame: At month 6, month 12 and month 24
Change in brain volumes
Change in brain volumes from baseline to month 24 and from month 6 to month 24
Time frame: From baseline to month 24 and from month 6 to month 24
Frequency of SAE/SAR and AESI during 24 months of treatment
Overall safety during 24 months of treatment
Time frame: From baseline to month 24
The frequency of immediate and delayed infusion reactions
The frequency of immediate and delayed infusion reactions during 24 months of treatment
Time frame: From baseline to month 24
Frequency of infections
The frequency of infections during 24 months of treatment
Time frame: From baseline to month 24
The frequency any malignancies
The frequency any malignancies during 24 months of treatment
Time frame: From baseline to month 24
Change in the quality of life (MSIS-29)
The Multiple Sclerosis Impact Scale (MSIS-29) is a 29-item self-report measure comprising 20 items associated with a physical scale and 9 items associated with a psychological scale, also translated and validated in Norwegian. Patients are asked about the impact of MS on day-to-day life in the last 2 weeks. All items have 5 response options from 1 (not at all) to 5 (extremely). Each of the 2 scales are scored by adding up the responses across items, then converting to a 0 to 100 scale, where 100 indicates greater impact of disease on daily function (worse health).
Time frame: From baseline to month 24
Change in Health related Anxiety and Depression as measured by HADS
The Hospital Anxiety and Depression Scale (HADS) is a questionnaire developed to screen anxiety and depression among patients in hospital settings. It consists of two subscales, one measuring anxiety, with seven items, and another measuring depression, with seven items. The two subscales are scored separately. The scale has been validated for use among MS patients as a screening instrument for symptoms of psychological distress. Higher scores indicate higher levels of anxiety and depression.
Time frame: From baseline to month 24
Change in the fatigue (FSMC)
The Fatigue scale for motor and cognitive functions (FSMC) is a method for evaluating fatigue in multiple sclerosis and other neurological conditions. The FSMC was developed and validated on a large sample of MS patients and healthy controls and includes subscales for both physical (motor) and mental (cognitive) aspects of fatigue. It was tested against 2 other validated fatigue scales (Fatigue Severity Scale and Modified Fatigue Impact Scale), and found to have better sensitivity and specificity than either of these instruments (Penner, Raselli et al. 2009). The FSMC has also undergone linguistic validation in over 20 languages, including Norwegian.
Time frame: From baseline to month 24
Change in EQ-5D score
The EQ-5D-5L self-report questionnaire essentially consists of 2 pages comprising: * The descriptive system (five dimensions of health; namely mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each dimension comprises three levels (no problems, some/moderate problems/extreme problems). * The EQ-VAS (visual analogue scale) which records the patient's self-rated health status on a vertical graduated (0 - 100) VAS.
Time frame: From baseline to month 24
Change in employment status
Patients will be asked about employment status at each visit (according to the following criteria: employed, unemployed, part-time employed, disability pension).
Time frame: From baseline to month 24
The frequency of anti-drug-antibodies
The frequency of anti-drug-antibodies during 24 months of treatment
Time frame: From baseline to month 24
Proportion of patients with hypogammaglobinemia
The proportion of patients with hypogammaglobinemia during 24 months of treatment
Time frame: From baseline to month 24
The proportion of patients with neutropenia
The proportion of patients with neutropenia during 24 months of treatment
Time frame: From baseline to month 24
Level and duration of B cell depletion
The level and duration of B cell depletion during 24 months of treatment
Time frame: From baseline to month 24
Level of CD27+ depletion
The level of CD27+ B memory cell depletion during 24 months of treatment
Time frame: From baseline to month 24
Change in serum levels of neurofilament (Nfl)
Change in serum levels of neurofilament (Nfl) during 24 months of treatment
Time frame: From baseline to month 24
Influence of different FcR genotypes
The influence of different FcR genotypes on B-cell depletion during 24 months of treatment
Time frame: From baseline to month 24
Influence of serum levels of vitamin D
The influence of serum levels of vitamin D on efficacy during 24 months of treatment
Time frame: From baseline to month 24
Change in cognition as measured by BICAMS
The BICAMS is a brief cognitive assessment that can be used also in study sites with staff members with no neuropsychological training (Walker, Osman et al. 2016) The tests address specific cognitive deficits that are common in MS patients, and the scales were chosen also for their psychometric qualities (reliability, validity and sensitivity) (Langdon, Amato et al. 2012). Tests must be administered during daytime, in a standardized manner, and in a quiet room. The order of tests will be fixed: the Symbol Digit Modalities Test (SDMT), Brief Visuospatial Memory Test-Revised (BVMT-R), and California Verbal Learning Test-II (CVLT-II). BICAMS has been validated for use in Norwegian MS-patients
Time frame: From baseline to month 24
Vaccination response
Vaccination response as measured by specific pneumococcus and/or influenza antibody titres in vaccinated patients during 24 months of treatment
Time frame: From baseline to month 24
Plan to share: No
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Multiple Sclerosis, Relapsing-Remitting→
Haukeland University Hospital