A Prospective Randomized Non-inferiority Trial Comparing Anti-CD20 Maintenance Versus De-Escalation Strategy In Relapsing-Remitting Multiple Sclerosis

NCT ID: NCT07189325

Last Updated: 2025-09-23

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-30
• Study Completion Date: 2030-09-30

Brief Summary

Multiple sclerosis (MS), the main central nervous system autoimmune disorder, is the first cause of non-traumatic disability in young adults and has thus significant individual consequences with elevated public health cost. It commonly starts during the third and fourth decades. Over the last twenty years, several disease-modifying therapies with variable benefit/risk profiles have been introduced leading to dramatic changes in the prognosis of MS.

First, several moderately effective therapies , with good safety profile, have allowed to decrease the frequency of relapses along with a possible, albeit limited, effect on medium- and long-term disability.

More recently highly effective therapies (HET), with immunosuppressive properties, have dramatically reduced clinical and MRI disease activity and significantly improved patient's prognosis.

Anti-CD20 therapies (B-cells depleting therapies, given either intravenous or subcutaneous), one of the main HET, have demonstrated higher efficacy than platform therapies in several phase 3 randomized clinical trials and their use within the very first years of the disease seems to be associated with improved long-term outcomes.

Taking all of this into account, the investigators hypothesize that RRMS patients who experience a de-escalation from anti-CD20 therapies to platform therapies after 40 years will not experience disease activity accrual and disability worsening.

Conditions

Relapsing-Remitting Multiple Sclerosis (RRMS); Anti-CD20 Therapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Experimental Group

Patients randomized in the experimental group will be treated with platform therapies (Dimethyl Fumarate, Diroximel fumarate, Teriflunomide, Glatiramer Acetate, Beta-interferons) according to treatments' authorization from the day of randomization to M36.

Group Type: EXPERIMENTAL

Platform therapies (Dimethyl Fumarate, Teriflunomide, Glatiramer Acetate, Beta-interferons)

Intervention Type: DRUG

Patients randomized in the experimental group will be treated with platform therapies (Dimethyl Fumarate, Diroximel Fumarate, Teriflunomide, Glatiramer Acetate, Beta-interferons) according to treatments' authorization from the day of randomization to M36 described below.

Patients will receive appropriate information and recommendation for the initiation of the chosen platform treatment as mention in the SmPC by treating neurologist or a member of the investigating team. If therapies are not tolerated, a therapeutic switch to other platform therapies will be possible. Any switch to a disease modifying therapy not listed as platform therapy will be considered as a major protocol deviation (see statistics).

Patients are allowed to switch from any platform DMT to another platform DMT.

Control Group

Patients randomized in the control group will be treated every 6 months (or, up to one year, at the same interval dosing) for patients with anti-CD20 (ocrelizumab, rituximab) or every 4 weeks for patients with subcutaneous anti-CD20 (ofatumumab) from the day of randomization to M36.

Group Type: ACTIVE_COMPARATOR

Anti-CD20 therapies (Ocrelizumab, Rituximab, Ofatumumab)

Intervention Type: DRUG

Patients randomized in the control group will be treated every 6 months (or at previous extended interval dosing) for patients with anti-CD20 (Ocrelizumab, Rituximab) or every 4 weeks for patients with subcutaneous anti-CD20 (Ofatumumab) from the day of randomization to M36. If therapies are not tolerated, a therapeutic switch to other anti-CD20 therapy will be possible. Any switch to a disease modifying therapy not listed as anti-CD20 therapy will be considered as major protocol deviation (see statistics).

Patients are allowed to switch from any anti-CD20 to another anti-CD20.

Interventions

Platform therapies (Dimethyl Fumarate, Teriflunomide, Glatiramer Acetate, Beta-interferons)

Patients randomized in the experimental group will be treated with platform therapies (Dimethyl Fumarate, Diroximel Fumarate, Teriflunomide, Glatiramer Acetate, Beta-interferons) according to treatments' authorization from the day of randomization to M36 described below.

Patients will receive appropriate information and recommendation for the initiation of the chosen platform treatment as mention in the SmPC by treating neurologist or a member of the investigating team. If therapies are not tolerated, a therapeutic switch to other platform therapies will be possible. Any switch to a disease modifying therapy not listed as platform therapy will be considered as a major protocol deviation (see statistics).

Patients are allowed to switch from any platform DMT to another platform DMT.

Intervention Type: DRUG

Anti-CD20 therapies (Ocrelizumab, Rituximab, Ofatumumab)

Patients randomized in the control group will be treated every 6 months (or at previous extended interval dosing) for patients with anti-CD20 (Ocrelizumab, Rituximab) or every 4 weeks for patients with subcutaneous anti-CD20 (Ofatumumab) from the day of randomization to M36. If therapies are not tolerated, a therapeutic switch to other anti-CD20 therapy will be possible. Any switch to a disease modifying therapy not listed as anti-CD20 therapy will be considered as major protocol deviation (see statistics).

Patients are allowed to switch from any anti-CD20 to another anti-CD20.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients ≥40 years at inclusion
• Patients with relapsing remitting multiple sclerosis at inclusion (according to 2017 McDonald criteria) treated with anti-CD20 for at least the last 3 years. For patients treated with IV ocrelizumab or rituximab at extended interval dosing, a maximum interval of 12 months between perfusions during the year before inclusion visit is required.
• No evidence of disease activity for the last 3 years on anti-CD20 (No relapse AND no new/enlarged MRI lesion)
• Brain MRI performed according to OFSEP protocol within a maximum of 6 months before randomization

• Secondary or primary progressive MS at inclusion
• Previous experience of treatment failure in patients treated with natalizumab, fingolimod, rituximab, ocrelizumab, mitoxantrone, alemtuzumab or cladribine
• Treatment with high dose corticosteroids during the 30 days preceding inclusion
• Contraindication to MRI
• Severely immunocompromised state
• Current severe active infection
• Known active malignancy
• Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease
• Severe hepatic impairment (Child-Pugh class C)
• Significantly impaired bone marrow function or significant anaemia, leukopenia, neutropenia or thrombocytopenia
• Severe renal impairment undergoing dialysis
• Severe hypoproteinaemia, e.g. in nephrotic syndrome
• Current severe depression and/or suicidal ideation
• Suspected or confirmed progressive multifocal leukoencephalopathy (PML)
• Any condition that, in the opinion of the investigator, would interfere with the interpretation of patient safety or place the patient at high risk for treatment-related complications
• Participation in another therapeutic trial in the last 6 months
• Protected population according to articles of the French Public Health Code (e.g. patients under law protection, prisoners, pregnant, parturient or lactating women, and patients under guardianship/curatorship)
• All women of childbearing age not using effective contraception during the study
• Subjects not covered by public health insurance
• Failure to obtain written informed consent after a reflection period

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Montpellier

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Neurology Department, Hospital Gui de Chauliac

Montpellier, , France

Countries

France

Central Contacts

Xavier AYRIGNAC, Medical Doctor

Role: CONTACT

x-ayrignac@chu-montpellier.fr

+33 4 67 33 74 13

Facility Contacts

Xavier Ayrignac, Medical Doctor

Role: primary

x-ayrignac@chu-montpellier.fr

+33 4 67 33 74 13

Other Identifiers

2024-513292-40-00

Identifier Type: CTIS

Identifier Source: secondary_id

RECHMPL23_0397

Identifier Type: -

Identifier Source: org_study_id