Relapsing Remitting Multiple SclerosisPhase 3OVERLORD-MSNCT04578639
Ocrelizumab VErsus Rituximab Off-Label at the Onset of Relapsing MS Disease
A Phase 3 study testing Rituximab and Ocrelizumab in people with Relapsing Remitting Multiple Sclerosis, run by Haukeland University Hospital at 12 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Relapsing Remitting Multiple Sclerosis
- What is being tested?
- Rituximab and Ocrelizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 214 participants
- Where
- 12 sitesin 2 countries
- Study dates
- 2 Nov 2020to 14 Sep 2025
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Male and female patients, treatment naïve, and aged between 18 and 60 years included
- Women of childbearing potential1 (WOCBP) able and willing to use highly effective methods of birth control2 per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly for the duration of the study OR until 3 months after last dose administered.
- A diagnosis of RRMS according to the 2017 revised diagnostic criteria of McDonald (Thompson, Banwell et al. 2018) within the last 12 months.
- Disease activity defined as ≥ 1 relapse3 or ≥ 1 new MRI lesion during the last 12 months
- EDSS score ≤ 4.0
- Absence of comorbidity or drug abuse that preclude study participation
Show all 9Show fewer
- Able to complete treatment or follow-up visits in the study (e.g. no contraindications for MRI or plans of moving)
- Able to understand written and spoken Norwegian or English
- Capable of giving signed informed consent as described in Appendix 1.2 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Who cannot join
- Known hypersensitivity or other known side effects for any of the study medications, including co-medications such as high glucocorticosteroids
- A diagnosis of primary progressive MS according to the revised diagnostic criteria of McDonald (Thompson, Banwell et al. 2018)
- A disease course of secondary progressive MS (Lublin, Reingold et al. 2014)
- Any ongoing infection, including tuberculosis, hepatitis virus or HIV, as well as hepatitis B surface antigen positivity and/or hepatitis C PCR positivity verified at screening visit.
- Prior or current psychiatric illness, mental deficiency or cognitive dysfunction influencing the patient ability to make an informed consent or comply with the treatment and follow-up phases of this protocol.
- Cardiac insufficiency, cardiomyopathy, significant cardiac dysrhythmia, unstable or advanced ischemic heart disease (NYHA III or IV)
Show all 19Show fewer
- Active malignancy or prior history of malignancy except localized basal cell, squamous skin cancer or carcinoma in situ of the cervix.
- WBC < 1.5 x 109/L if not caused by a reversible effect of documented ongoing medication. If WBC < 1.5 x 109/L is caused by a reversible effect of documented ongoing medication the WBC count must be > 1,5 x 109/L before start of study treatment.
- Platelet (thrombocyte) count < 100 x 109/L
- ALAT and/or ASAT more than 2 times the upper normal reference limit (ULN)
- Serum creatinine > 200 µmol/L
- Serum bilirubin > ULN
- Pregnancy or lactating female patients
- Any disease that can influence the patient safety and compliance, or the evaluation of disability
- History of serious or life-threatening infusion reaction to ocrelizumab or rituximab, if previously treated with these medications for other diseases than MS
- Previous use of MS-therapies such as natalizumab, fingolimod, interferons, glatiramer acetate, dimethyl fumarate, teriflunomide, cladribine, rituximab, alemtuzumab, ocrelizumab, hematopoietic stem cell therapy (HSCT) or other immunosuppression therapies with long lasting effects, or any other disease modifying therapy (DMT) for MS. If any of these medications have been used against other diseases than MS, patients can be included if the medications have not been used the previous year before enrollment.
- Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study (s), or receiving other investigational treatment(s). Patients participating in a purely observational trial will not be excluded.
- Presence of metallic objects implanted in the body, or allergy to MRI contrast that would preclude the ability of the patient to safely have MRI exams
- Current alcohol or drug dependencies
Trial locations and contacts
12 sites in 2 countries.
12 sites in 2 countries
Norway11 sites
Haukeland University Hospital
Bergen
Nordlandsykehuset HF
Bodø
Vestre Viken sykehus
Drammen
Sørlandet Sykehus
Kristiansand
Molde sjukehus
Molde
Sykehuset Namsos
Namsos
Oslo University Hospital HF
Oslo, 0424
Akershus University Hospital
Oslo, 1478
Sykehuset Telemark
Skien
Stavanger University Hospital HF
Stavanger, 4068
University Hospital North Norway
Tromsø
About this study
Official title: Ocrelizumab VErsus Rituximab Off-Label at the Onset of Relapsing
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.
Read the detailed description
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.
- Conditions
- Relapsing Remitting Multiple Sclerosis
- Being tested
- Rituximab, Ocrelizumab
- Keywords
- RRMS, MS
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Also called 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.
OcrelizumabDrug
Also called ocrevus
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.
| Study group | Role | What they receive |
|---|---|---|
| Rituximab | Experimental | 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 Receives: Drug: Rituximab |
| Ocrelizumab | Active comparator | 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 Receives: Drug: Ocrelizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion without new MRI activity
Proportion of patients with no new or enlarging T2-weighted brain MRI lesions
Measured: From month 6 (re-baseline) to month 24
Secondary outcomes (20)
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.
Measured: 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.
Measured: From baseline to month 24
Annual relapse rate
The annual relapse rate from baseline to month 24
Measured: From baseline to month 24
Proportion of patients without relapses
Proportion of patients without relapses from baseline to month 24
Measured: 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).
Measured: 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).
Measured: 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)
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: From baseline to month 24
Frequency of infections
The frequency of infections during 24 months of treatment
Measured: From baseline to month 24
The frequency any malignancies
The frequency any malignancies during 24 months of treatment
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: From baseline to month 24
The frequency of anti-drug-antibodies
The frequency of anti-drug-antibodies during 24 months of treatment
Measured: From baseline to month 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2020
- Study start2 Nov 2020
- Primary completion14 Aug 2025 (estimated)
- Study completion14 Sep 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Relapsing Remitting Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Haukeland University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 214 participants (actual)
Sponsor and investigators
- Lead sponsor
- Haukeland University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital, Akershus, Oslo University Hospital, Helse Stavanger HF, St. Olavs Hospital, University Hospital of North Norway
- Responsible party
- Sponsor
- Investigators
- Kjell-Morten Myhr, MD, Study director, Haukeland University HospitalØivind Torkildsen, MD, Principal investigator, Haukeland University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04578639
- Sponsor's protocol ID
- 2020-001205-23
- Acronym
- OVERLORD-MS
- Status last verified
- Jun 2025
- First submitted
- 22 Sep 2020
- Last updated
- 27 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Serkland TT, Oma AF, Hallin EI, Overas MH, Nygaard GO, Myhr KM, Torkildsen O, Roblitz S, Skrede S. Pharmacokinetic-Pharmacodynamic Modelling of Repeated Ocrelizumab Dosing in Relapsing-Remitting Multiple Sclerosis. Clin Pharmacokinet. 2026 Aug 28. doi: 10.1007/s40262-026-01692-8. Online ahead of print.
PubMed 42663866Torkildsen O, Brustad HK, Hogestol EA, Alstadhaug KB, Bhan A, Flemmen HO, Habbestad A, Hoglund RAA, LeBlanc M, Lopen P, Lorentzen AR, Morsund AH, Lossius A, Lundby R, Nygaard GO, Rod BE, Simonsen CS, Steffensen L, Torgauten H, Piehl F, Wergeland S, Myhr KM; OVERLORD-MS Investigators. Rituximab versus Ocrelizumab in Newly Diagnosed Relapsing Multiple Sclerosis. N Engl J Med. 2026 Jul 2;395(1):44-53. doi: 10.1056/NEJMoa2600993.
PubMed 42384870
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ocrelizumab VErsus Rituximab Off-Label at the Onset of Relapsing
- ClinicalTrials.gov ID
- NCT04578639
- Acronym / sponsor ID
- OVERLORD-MS / 2020-001205-23
- Conditions
- Relapsing Remitting Multiple Sclerosis
- Keywords
- RRMS, MS
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 214 participants (actual)
- Lead sponsor
- Haukeland University HospitalUniversity, hospital or other
- Collaborators
- University Hospital, Akershus, Oslo University Hospital, Helse Stavanger HF, St. Olavs Hospital, University Hospital of North Norway
- Study start
- 2 Nov 2020 (actual)
- Primary completion
- 14 Aug 2025 (estimated)
- Study completion
- 14 Sep 2025 (estimated)
- First posted
- 8 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Rituximab | Experimental | Drug: RituximabRituximab 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 |
| Ocrelizumab | Active comparator | Drug: OcrelizumabOcrelizumab 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 |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Male and female patients, treatment naïve, and aged between 18 and 60 years included
- Women of childbearing potential1 (WOCBP) able and willing to use highly effective methods of birth control2 per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly for the duration of the study OR until 3 months after last dose administered.
- A diagnosis of RRMS according to the 2017 revised diagnostic criteria of McDonald (Thompson, Banwell et al. 2018) within the last 12 months.
- Disease activity defined as ≥ 1 relapse3 or ≥ 1 new MRI lesion during the last 12 months
- EDSS score ≤ 4.0
Key exclusion criteria (19 listed)
- Known hypersensitivity or other known side effects for any of the study medications, including co-medications such as high glucocorticosteroids
- A diagnosis of primary progressive MS according to the revised diagnostic criteria of McDonald (Thompson, Banwell et al. 2018)
- A disease course of secondary progressive MS (Lublin, Reingold et al. 2014)
- Any ongoing infection, including tuberculosis, hepatitis virus or HIV, as well as hepatitis B surface antigen positivity and/or hepatitis C PCR positivity verified at screening visit.
- Prior or current psychiatric illness, mental deficiency or cognitive dysfunction influencing the patient ability to make an informed consent or comply with the treatment and follow-up phases of this protocol.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RituximabAlso: mabtheraA 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. | Drug | Rituximab |
| OcrelizumabAlso: ocrevusA 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. | Drug | Ocrelizumab |
Primary outcome
Proportion without new MRI activity
Time frame: From month 6 (re-baseline) to month 24
Proportion of patients with no new or enlarging T2-weighted brain MRI lesions
20 secondary outcomes
Proportion of patients with 6-months confirmed disability progression (6M-CDP)
Time frame: From baseline to month 24
Proportion of patients with 6-months confirmed disability improvement (6M-CDI)
Time frame: From baseline to month 24
Annual relapse rate
Time frame: From baseline to month 24
Proportion of patients without relapses
Time frame: From baseline to month 24
Proportion of patients with 6M-CDP in T25FW
Time frame: From baseline to month 24
Proportion of patients with 6M-CDP in 9-HPT
Time frame: From baseline to month 24
Proportion of patients with 6M-CDP in SDMT
Time frame: From baseline to month 24
Proportion of patients with no new or enlarging T2-weighted brain MRI lesions
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
Time frame: At month 6, month 12 and month 24
Change in brain volumes
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
Time frame: From baseline to month 24
The frequency of immediate and delayed infusion reactions
Time frame: From baseline to month 24
Frequency of infections
Time frame: From baseline to month 24
The frequency any malignancies
Time frame: From baseline to month 24
Change in the quality of life (MSIS-29)
Time frame: From baseline to month 24
Change in Health related Anxiety and Depression as measured by HADS
Time frame: From baseline to month 24
Change in the fatigue (FSMC)
Time frame: From baseline to month 24
Change in EQ-5D score
Time frame: From baseline to month 24
Change in employment status
Time frame: From baseline to month 24
The frequency of anti-drug-antibodies
Time frame: From baseline to month 24
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2025.
- Derived from this study: PubMed 42663866Serkland TT, Oma AF, Hallin EI, Overas MH, Nygaard GO, Myhr KM, Torkildsen O, Roblitz S, Skrede S. Pharmacokinetic-Pharmacodynamic Modelling of Repeated Ocrelizumab Dosing in Relapsing-Remitting Multiple Sclerosis. Clin Pharmacokinet. 2026 Aug 28. doi: 10.1007/s40262-026-01692-8. Online ahead of print.
- Derived from this study: PubMed 42384870Torkildsen O, Brustad HK, Hogestol EA, Alstadhaug KB, Bhan A, Flemmen HO, Habbestad A, Hoglund RAA, LeBlanc M, Lopen P, Lorentzen AR, Morsund AH, Lossius A, Lundby R, Nygaard GO, Rod BE, Simonsen CS, Steffensen L, Torgauten H, Piehl F, Wergeland S, Myhr KM; OVERLORD-MS Investigators. Rituximab versus Ocrelizumab in Newly Diagnosed Relapsing Multiple Sclerosis. N Engl J Med. 2026 Jul 2;395(1):44-53. doi: 10.1056/NEJMoa2600993.
- Individual participant dataSharing planned: No
Related trials for Relapsing Remitting Multiple Sclerosis
Active, not recruiting
Myrosinase Bioactivated Gglucoraphanin for the Treatment of Neurodegenerative Diseases (GRA-MYR-ND)
PARKINSON DISEASE (Disorder), Multiple Sclerosis (MS) - Relapsing-remitting
Recruiting
Wearable Focal Vibration Therapy on Upper Extremity Function of People With Multiple Sclerosis: A Pilot Study
Multiple Sclerosis (MS) - Relapsing-remitting, Upper Extremity Dysfunction
Not yet recruiting
Treatment of Memory Retrieval Impairments in MS With HDtDCS to the LIFG in a Placebo Controlled Trial
Multiple Sclerosis, Relapsing-remitting Multiple Sclerosis (RRMS)
Recruiting
Monthly Monitoring of Plasma NfL in Treated Relapsing-remitting Multiple Sclerosis to Detect Persistent Infraclinical Disease Activity
Multiple Sclerosis (MS) - Relapsing-remitting
Active, not recruitingPhase 4
Safety and Efficacy Study of Fingolimod in Taiwanese Adults (≥ 20years) With Relapsing Remitting Multiple Sclerosis
Multiple Sclerosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kjell-Morten Myhr, MD study director
Haukeland University Hospital
Øivind Torkildsen, MD principal investigator
Haukeland University Hospital
12 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rituximab and Ocrelizumab in people with Relapsing Remitting Multiple Sclerosis, run by Haukeland University Hospital at 12 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 27 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Norway, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion without new MRI activity (time frame: From month 6 (re-baseline) to month 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04578639, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2025.