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

Not Applicable

Not yet recruiting

• Conditions: Anti-CD20 Therapy; Relapsing-Remitting Multiple Sclerosis (RRMS)
• Interventions: Drug: Platform therapies (Dimethyl Fumarate, Teriflunomide, Glatiramer Acetate, Beta-interferons); Drug: Anti-CD20 therapies (Ocrelizumab, Rituximab, Ofatumumab)

• Registration Number: NCT07189325
• Lead Sponsor: University Hospital, Montpellier

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-07-23
• Status Verified: 2025-09
• Study Start: 2025-09-01
• Study First Submitted QC: 2025-09-17
• Last Update Submitted: 2025-09-17
• Study First Posted: 2025-09-23
• Last Update Posted: 2025-09-23
• Primary Completion: 2030-09
• Study Completion: 2030-09-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental Group	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.
Control Group	Anti-CD20 therapies (Ocrelizumab, Rituximab, Ofatumumab)	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.

Primary Outcome Measures

Name	Time	Method
Relapse	From Day 0 to Month 36	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.
New/enlarged MRI lesions	From Day 0 to Month 36	New/enlarged T2/FLAIR lesion on MRI scans to assess MRI disease activity .

Secondary Outcome Measures

Name	Time	Method
Relapse	From Day 0 to Month 36	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
Expanded Disability Status Scale (EDSS)	From Day 0 to Month 36	EDSS to compare disability between both groups. This score is expressed from 0 (no disability) to 10 (multiple sclerosis-related death) and incorporates evaluation of the following neurological systems (pyramidal, sensory, cerebellar, sphincter, cognitive, and cranial pairs)
Brain MRI (T2/FLAIR Lesions)	From Day 0 to Month 36	MRI scans to compare new/enlarged T2/FLAIR lesions between both groups.
Number of adverse events and severe adverse events	From Day 0 to Month 36	To compare adverse events and severe adverse events between both groups.
Number of infections and serious infections	From Day 0 to Month 36	To compare infections and serious infections between both groups.
B-cell count (CD19/CD20 B cells)	From Day 0 to Month 36	B-cell count (CD19/CD20 B cells) to compare C• B-cells repopulation (CD19/CD20+ B-cells) between both groups.
Serum immunoglobulin (IgG, IgA, IgM) levels	From Day 0 to Month 36	Serum immunoglobulin (IgG, IgA, IgM) levels to compare • Immunoglobulin (IgG, A, M) levels changes between both groups.

Trial Locations

Locations (1)

Neurology Department, Hospital Gui de Chauliac; 🇫🇷 Montpellier, France