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

NCT07189325 | Not Yet Recruiting Phase 3 DMC

• 2 other identifiers: RECHMPL23_03972024-513292-40-00
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 1

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

Keywords

Multiple Sclerosis; High efficacy therapies; de-escalation; adverse events; relapses; escalation

Outcome Measures

Primary Outcomes (2)

• Relapse

  Presence of at least one clinical relapse defined as new or worsening symptoms related to MS resulting in objective signs on neurological examination in the absence of any potential trigger not related to MS.

  From Day 0 to Month 36

• New/enlarged MRI lesions

  New/enlarged T2/FLAIR lesion on MRI scans to assess MRI disease activity .

  From Day 0 to Month 36

Secondary Outcomes (7)

• Relapse

  From Day 0 to Month 36

• Expanded Disability Status Scale (EDSS)

  From Day 0 to Month 36

• Brain MRI (T2/FLAIR Lesions)

  From Day 0 to Month 36

• Number of adverse events and severe adverse events

  From Day 0 to Month 36

• Number of infections and serious infections

  From Day 0 to Month 36

Other Outcomes (7)

• Multiple Sclerosis Functional Composite (MSFC)

  From Day 0 to Month 36

• The Computerised Speed Cognitive Test (CSCT)

  From Day 0 to Month 36

• Neurofilament Light Chains (sNfL) Serum Concentration

  From Day 0 to Month 36

Study Arms (2)

Experimental Group

EXPERIMENTAL

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.

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

Control Group

ACTIVE COMPARATOR

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.

Drug: Anti-CD20 therapies (Ocrelizumab, Rituximab, Ofatumumab)

Interventions

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

Experimental Group

Anti-CD20 therapies (Ocrelizumab, Rituximab, Ofatumumab) 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.

Control Group

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Previous experience of treatment failure in patients treated with natalizumab, fingolimod, rituximab, ocrelizumab, mitoxantrone, alemtuzumab or cladribine
• 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

Sponsors & Collaborators

• University Hospital, Montpellier: lead

Study Sites (1)

Neurology Department, Hospital Gui de Chauliac

Montpellier, 34295, France

Location

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis; Recurrence

Interventions

Dimethyl Fumarate; teriflunomide; Glatiramer Acetate; Interferon-beta; ocrelizumab; Rituximab; ofatumumab

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Fumarates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Peptides; Amino Acids, Peptides, and Proteins; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Proteins; Biological Factors; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Central Study Contacts

Xavier AYRIGNAC, Medical Doctor

CONTACT

+33 4 67 33 74 13; x-ayrignac@chu-montpellier.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multi-center, prospective, comparative, randomized into two parallel (1:1) arms, open to treatment with blinded endpoint (PROBE) non-inferiority trial comparing, over 3 years, the maintenance of anti-CD20 therapies and a de-escalation strategy: * 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. * 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. In both groups, each patient will have a treating neurologist and a blinded examinator who will perform blinded EDSS evaluations and assessment of suspected relapses.

Study Record Dates

• First Submitted: July 23, 2025
• First Posted: September 23, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): September 1, 2030
• Last Updated: September 23, 2025

Record last verified: 2025-09

Locations

FR (1)