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

Phase 1

• Conditions: Remitting Relapsing Multiple Sclerosis; MedDRA version: 21.1Level: PTClassification code 10063399Term: Relapsing-remitting multiple sclerosisSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2020-001205-23-SE
• Lead Sponsor: Helse Bergen HF, Haukeland University Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-12-06
• Last Update Posted: 19 February 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 208

Inclusion Criteria

1.Male and female patients, treatment naïve, and aged between 18 and 60 years included
2.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 12 months after last dose administered to comply with CTFG Contraception guidance version 1.1 (CTFG 21/09/2020).
3.A diagnosis of RRMS according to the 2017 revised diagnostic criteria of McDonald (Thompson, Banwell et al. 2018) within the last 12 months.
4.Disease activity defined as = 1 relapse3 or = 1 new MRI lesion4 during the last 12 months
5.EDSS score = 4.0
6.Absence of comorbidity or drug abuse that preclude study participation
7.Able to complete treatment or follow-up visits in the study (e.g. no contraindications for MRI or plans of moving)
8. Able to understand written and spoken Norwegian or Swedish.
9. 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 208
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Known hypersensitivity or other known side effects for any of the study medications, including co-medications such as high glucocorticosteroids
2.A diagnosis of primary progressive MS according to the revised diagnostic criteria of McDonald (Thompson, Banwell et al. 2018)
3.A disease course of secondary progressive MS (Lublin, Reingold et al. 2014)
4.Any ongoing infection, including tuberculosis, hepatitis virus or HIV, as well as hepatitis B surface antigen positivity and/or hepatitis C seropositivity.
5.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.
6.Cardiac insufficiency, cardiomyopathy, significant cardiac dysrhythmia, unstable or advanced ischemic heart disease (NYHA III or IV)
7.Active malignancy or prior history of malignancy except localized basal cell, squamous skin cancer or carcinoma in situ of the cervix.
8.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.
9.Platelet (thrombocyte) count < 100 x 109/L
10.ALAT more than 2 times the upper normal reference limit (ULN)
11.Serum creatinine > 200 µmol/L
12.Serum bilirubin > ULN
13.Pregnancy or lactating female patients
14.Any disease that can influence the patient safety and compliance, or the evaluation of disability
15.History of serious or life-threatening infusion reaction to ocrelizumab or rituximab, if previously treated with these medications for other diseases than MS
16. 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.
17. 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.
18.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.
19.Current alcohol or drug dependencies.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary end point(s): The primary endpoint is to determine the difference in efficacy and safety between rituximab and ocrelizumab according to the following criteria:<br>•Proportion of patients with no new or enlarging T2-weighted brain MRI lesions from month 6 (re-baseline) to month 24<br>;Timepoint(s) of evaluation of this end point: From re-baseline at 6 months to 24 months.;Main Objective: To demonstrate non-inferiority of rituximab compared to ocrelizumab with regards to efficacy and safety in treatment of naïve RRMS patients, diagnosed within the last 12 months.<br>;Secondary Objective: Not applicable