Non-inferiority Study of Rituximab Compared to Ocrelizumab in Relapsing MS

NCT ID: NCT05834855

Last Updated: 2023-04-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-04-30

Study Completion Date

2027-05-31

Brief Summary

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Rationale: Ocrelizumab is widely and effectively used to treat relapsing multiple sclerosis (RMS). Phase II studies and data from large patient cohorts indicate that rituximab, another anti-CD20 monoclonal antibody, is probably equally effective and safe as ocrelizumab in the treatment of RMS. An advantage of rituximab is a considerably lower price. Therefore we will start a study aimed at demonstrating non-inferiority of rituximab compared to ocrelizumab in RMS. If non-inferiority of rituximab can be shown, important reductions in the cost of treatment of RMS will be possible, without loss of efficacy.

Objective: Evaluating the efficacy and safety of ritixumab compared to ocrelizumab in the treatmens of RMS.

Study design: Randomized double blind multi-centre non-inferiority study of rituximab compared to ocrelizumab in 200 patients with RMS. The trial duration will be 30 months

Study population: The study population consists of 200 adult RMS patiens with an indication to start anti-CD20 monoclonal antibody treatment.

Intervention: Patients will be randomized 1:1 into the standard group (ocrelizumab treatment) or the experimental group (rituximab treatment).

Main study parameters: To conclude non-inferiority of rituximab there will be one primary endpoint: the proportion of patients free of inflammatory disease activity (defined as: new or enlarged T2 lesions) between week 24 (M6) and week 96 (M24) of treatment in each arm. Secondary trial endpoints are presence and number of clinical relapses,T2 and contrast enhancing lesion volumes, brain volume and brain volume changes, disease progression (defined as clinically relevant change on any of the measures: EDSS, T25FW, 9HPT, SDMT), biochemical parameters such as lipidomics and neurofilament light (NfL), immunological parameters, safety as measured by the number of (serious) adverse events ((S)AE), quality of life (EQ-5D-L) and treatment satisfaction (TSQM) and patient reported measures of MS impact (MSIS-29) and well-being (questionnaire on physical complaints)

Nature and extent of the burden and risk: Patients included in this study will be treated and monitored by MRI, clinical tests and laboratory tests according to existing protocols and will not be exposed to extra or unknown risks. They will have extra annual questionnaires and larger blood samples at some time points. There is extensive experience with both rituximab and ocrelizumab as efficacious and safe treatments of RMS.

Detailed Description

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Conditions

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Multiple Sclerosis Multiple Sclerosis, Relapsing-Remitting Demyelinating Autoimmune Diseases, CNS Autoimmune Diseases of the Nervous System Nervous System Diseases Demyelinating Diseases

Keywords

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ocrelizumab rituximab non-inferiority

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Multicenter randomized controlled double-blind non-inferiority trial in The Netherlands
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
The patient, site personnel administrating infusions, and the treating and evaluating neurologist and study nurse will all be blinded

Study Groups

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Ocrelizumab

The standard group will receive ocrelizumab (600 mg, the first dosage given in two infusion of 300 mg with a two week interval) following the current treatment protocol

Group Type NO_INTERVENTION

No interventions assigned to this group

Rituximab

The experimental group will receive rituximab (1000 mg). Rituximab will be given intravenously. To ensure blinding of treatment allocation two dosages of 500 mg with a two week interval will be given instead of one initial dosage of 1000 mg of rituximab to mimic the ocrelizumab protocol

Group Type EXPERIMENTAL

Rituximab

Intervention Type DRUG

Treatment with rituximab

Interventions

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Rituximab

Treatment with rituximab

Intervention Type DRUG

Other Intervention Names

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MabThera Truxima Ruxience Rixathon

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Stichting Treatmeds

UNKNOWN

Sponsor Role collaborator

Amsterdam UMC, location VUmc

OTHER

Sponsor Role lead

Responsible Party

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Eva M.M. Strijbis

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Bob van Oosten, Dr

Role: PRINCIPAL_INVESTIGATOR

Amsterdam UMC, location VUmc

Locations

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Amsterdam UMC, location VUmc

Amsterdam, , Netherlands

Site Status RECRUITING

Countries

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Netherlands

Central Contacts

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Lisa Schoof, Msc

Role: CONTACT

Phone: 650087853

Email: [email protected]

Eva Strijbis, Dr.

Role: CONTACT

Phone: 204442182

Email: [email protected]

Facility Contacts

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B. van Oosten, Dr.

Role: primary

E. Strijbis, Dr.

Role: backup

Other Identifiers

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Anti-CD20 in RMS

Identifier Type: -

Identifier Source: org_study_id