Comparing Rituximab and Ocrelizumab for Treating Relapsing Multiple Sclerosis

Non-inferiority Study of Rituximab Compared to Ocrelizumab in Relapsing Multiple Sclerosis

This study is testing if rituximab works just as well as ocrelizumab for treating relapsing multiple sclerosis in adults.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 200 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Amsterdam UMC, location VUmc (Academic / other)
• Drugs / interventions: alemtuzumab, ofatumumab, natalizumab, Ocrelizumab, rituximab, ritixumab
• Locations: 1 site (Amsterdam)
• Trial ID: NCT05834855 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the efficacy and safety of rituximab compared to ocrelizumab in patients with relapsing multiple sclerosis (RMS). It is a randomized, double-blind, multi-center non-inferiority study involving 200 adult participants who are eligible for anti-CD20 therapy. The study will last for 30 months and seeks to demonstrate that rituximab is as effective as ocrelizumab, potentially leading to significant cost savings in treatment without compromising patient outcomes.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older diagnosed with relapsing multiple sclerosis who require anti-CD20 therapy.

Not a fit: Patients with primary progressive MS or not-active secondary progressive MS may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more affordable treatment option for patients with relapsing multiple sclerosis.

How similar studies have performed: Previous studies have indicated that rituximab may be equally effective as ocrelizumab, suggesting a promising avenue for this non-inferiority approach.

Eligibility criteria

Inclusion Criteria:

1. Men and women aged 18 years and older
2. A diagnosis of relapsing MS according to the 2017 revised diagnostic criteria
3. 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
4. Able to understand written and spoken Dutch or English
5. Capable of giving signed informed consent including compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
6. Screening EDSS score ≤ 6.5 .

Exclusion Criteria:

Medical Conditions

1. A known allergy or other intolerability to RTX, OCR, gadolinium-based MRI contrast agents, or corticosteroids.
2. A diagnosis of primary progressive MS according to the diagnostic criteria.
3. A diagnosis of not-active secondary progressive MS.
4. 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.
5. A history of proven inflammatory bowel disease such as M. Crohn or ulcerative colitis
6. 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.
7. Cardiac disease that makes treatment with OCR or RTX contra-indicated as stated by the most recent SmPC
8. Active malignancy or prior history of malignancy that makes treatment with OCR or RTX contra-indicated as stated by the most recent SmPC.
9. WBC \< 1.5 x 109/L if not caused by a reversible effect of documented ongoing medication. If caused by a reversible effect of documented ongoing medication the WBC count must be \> 1,5 x 109/L before start of study treatment.
10. Platelet (thrombocyte) count \< 100 x 109/L
11. ALAT and/or ASAT more than 2 times the upper normal reference limit (ULN)
12. Serum creatinine \> 200 μmol/L
13. Serum bilirubin \> ULN
14. Serum IgG \< LLN
15. Pregnant or breast-feeding women
16. Women of childbearing potential (WOCBP) not able or willing to use highly effective methods of birth control per ICH M3 (R2) that result in failure rate of ≤ 1% per year when used consistently and correctly for the duration of the study OR until 3 months after last dose administered.
17. History of serious or life-threatening infusion reaction to OCR or RTX
18. Treatment with glucocorticoids or ACTH within one month prior to start of study treatment

    Prior/Concomitant Therapy
19. Previous use of second line MS-therapies cladribine, RTX, alemtuzumab, OCR, ofatumumab, hematopoietic stem cell therapy (HSCT) or other immunosuppression therapies with long lasting effects. Mitoxantrone is allowed if used \> 1 year before enrolment. If any of these medications have been used for indications other than MS, patients can be included if the medications have not been used the year before enrolment. Previous treatment with natalizumab is allowed if the reason to switch was disease activity (so not allowed in for example cases that switch from natalizumab to anti-CD20 therapy because of JCV positivity).
20. Concomitant use of systemic immunosuppressive medication (except corticosteroids for symptomatic treatment of relapses).

    Prior/Concurrent Clinical Study Experience
21. Currently enrolled in another investigational device or drug study, or less than 30 days since ending of another investigational device or drug study (s), or receiving other investigational treatment(s). Patients participating in a purely observational studies will be allowed to participate.

    Lifestyle
22. Current alcohol or drug dependencies.

    Diagnostic assessments
23. Presence of metallic objects implanted in the body, that would preclude the ability of the patient to safely have MRI exams.
24. Not willing to undergo MRI scans with i.v. gadolinium injections

Where this trial is running

Amsterdam

• Amsterdam UMC, location VUmc — Amsterdam, Netherlands (Recruiting)

Study contacts

• Principal investigator: Bob van Oosten, Dr — Amsterdam UMC, location VUmc
• Study coordinator: Lisa Schoof, Msc

Conditions Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; ocrelizumab; rituximab