Ocrelizumab VErsus Rituximab Off-Label at the Onset of Relapsing MS Disease

NCT04578639 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: 2020-001205-23
• Study Type: interventional
• Target: 214
• Locations: 2 countries
• Sites: 12

Brief 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.

Conditions

Relapsing Remitting Multiple Sclerosis

Keywords

RRMS; MS

Outcome Measures

Primary Outcomes (1)

• Proportion without new MRI activity

  Proportion of patients with no new or enlarging T2-weighted brain MRI lesions

  From month 6 (re-baseline) to month 24

Secondary Outcomes (20)

• Proportion of patients with 6-months confirmed disability progression (6M-CDP)

  From baseline to month 24

• Proportion of patients with 6-months confirmed disability improvement (6M-CDI)

  From baseline to month 24

• Annual relapse rate

  From baseline to month 24

• Proportion of patients without relapses

  From baseline to month 24

• Proportion of patients with 6M-CDP in T25FW

  From baseline to month 24

Other Outcomes (9)

• Proportion of patients with hypogammaglobinemia

  From baseline to month 24

• The proportion of patients with neutropenia

  From baseline to month 24

• Level and duration of B cell depletion

  From baseline to month 24

Study Arms (2)

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

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

Drug: Ocrelizumab

Interventions

Rituximab DRUG

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

Rituximab

Ocrelizumab DRUG

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

Ocrelizumab

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Haukeland University Hospital: lead
• University Hospital, Akershus: collaborator
• Oslo University Hospital: collaborator
• Helse Stavanger HF: collaborator
• St. Olavs Hospital: collaborator
• University Hospital of North Norway: collaborator

Study Sites (12)

Haukeland University Hospital

Bergen, Norway

Location

Nordlandsykehuset HF

Bodø, Norway

Location

Vestre Viken sykehus

Drammen, Norway

Location

Sørlandet Sykehus

Kristiansand, Norway

Location

Molde sjukehus

Molde, Norway

Location

Sykehuset Namsos

Namsos, Norway

Location

Oslo University Hospital HF

Oslo, 0424, Norway

Location

Akershus University Hospital

Oslo, 1478, Norway

Location

Sykehuset Telemark

Skien, Norway

Location

Stavanger University Hospital HF

Stavanger, 4068, Norway

Location

University Hospital North Norway

Tromsø, Norway

Location

Karolinska Hospital

Stockholm, Sweden

Location

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

Rituximab; ocrelizumab

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Kjell-Morten Myhr, MD

  Haukeland University Hospital

  STUDY DIRECTOR

• Øivind Torkildsen, MD

  Haukeland University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The investigators as well as the study participants, are blinded to the treatment allocation status. To assure this double-blinding, a dedicated "treating nurse" will be appointed at each study centre. Information about randomization (treatment arm) will be given directly through electronic communication (automatic generated email) from Viedoc™ to the treating nurse as soon as the randomization procedure has been performed. Only the treating nurse will have access to information concerning which treatment arm the patient is allocated to. The treating nurse will order the medicine from the pharmacy and perform the dilution in NaCl (in an infusion bag). An evaluating nurse and evaluating neurologist (blinded to study drug) will perform the clinical evaluation of the patient while the patient receives the medication and as part of registration of study information. The evaluating neurologist and evaluating nurse will not be able to access the randomization procedure in Viedoc™.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 22, 2020
• First Posted: October 8, 2020
• Study Start: November 2, 2020
• Primary Completion: August 14, 2025
• Study Completion: September 14, 2025
• Last Updated: June 27, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1); NO (11)