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NCT Number: NCT07189325

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

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.

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Key information

Conditions

Relapsing-remitting Multiple Sclerosis (rrMS) Anti-CD20 Therapy Autoimmune Diseases Autoimmune Diseases of the Nervous System Demyelinating Autoimmune Diseases, CNS Demyelinating Diseases Disease Attributes Immune System Diseases Multiple Sclerosis Multiple Sclerosis, Relapsing-Remitting Nervous System Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Recurrence

Age range

40 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Neurology Department, Hospital Gui de Chauliac

Montpellier, 34295, France

Location status: Recruiting

Location contact

Xavier Ayrignac, Medical Doctor

CONTACT

[email protected]

+33 4 67 33 74 13

Xavier Ayrignac, Medical Doctor

PRINCIPAL_INVESTIGATOR

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Non-inclusion criteria :

  • 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

Treatment and study plan

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.

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.

Primary outcomes

  1. Relapse

    Time frame: 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.

  2. New/enlarged MRI lesions

    Time frame: From Day 0 to Month 36

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

Secondary outcomes

  1. Relapse

    Time frame: 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

  2. Expanded Disability Status Scale (EDSS)

    Time frame: 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)

  3. Brain MRI (T2/FLAIR Lesions)

    Time frame: From Day 0 to Month 36

    MRI scans to compare new/enlarged T2/FLAIR lesions between both groups.

  4. Number of adverse events and severe adverse events

    Time frame: From Day 0 to Month 36

    To compare adverse events and severe adverse events between both groups.

  5. Number of infections and serious infections

    Time frame: From Day 0 to Month 36

    To compare infections and serious infections between both groups.

  6. B-cell count (CD19/CD20 B cells)

    Time frame: 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.

  7. Serum immunoglobulin (IgG, IgA, IgM) levels

    Time frame: From Day 0 to Month 36

    Serum immunoglobulin (IgG, IgA, IgM) levels to compare • Immunoglobulin (IgG, A, M) levels changes between both groups.

Other outcomes

  1. Multiple Sclerosis Functional Composite (MSFC)

    Time frame: From Day 0 to Month 36

    MSFC including the 9-Hole Peg Test (9HPT), Timed 25 Foot Walk (T25FW), and Paced Auditory Serial Addition Test (PASAT) to compare functional disability between both groups.

  2. The Computerised Speed Cognitive Test (CSCT)

    Time frame: From Day 0 to Month 36

    CSCT a cognitive test to compare the detection of information speed disorders between both groups.

  3. Neurofilament Light Chains (sNfL) Serum Concentration

    Time frame: From Day 0 to Month 36

    Neurofilament Light Chains (sNfL) Serum Concentration to compare change of serum Neurofilament light chains bteween both groups.

  4. The 5 Level European Quality of Life 5 Dimensions (EQ5D-5L)

    Time frame: From Day 0 to Month 36

    EQ5D-5L questionnaire to compare the generic quality of life between both groups.

  5. MUSICARE

    Time frame: From Day 0 to Month 36

    MUSICARE, self-report questionnaire to compare the experience of both patients and caregivers of quality of care in MS between both groups.

  6. CD27+ memory B-cell count

    Time frame: From Day 0 to Month 36

    CD27+ memory B-cell count to compare CD27+ memory B-cells repopulation between both groups.

  7. Patient-level cost

    Time frame: From Day 0 to Month 36

    Healthcare consumption collected via data from the SNDS (French Health Insurance Database) to assess medico-economic impact.

Study contacts

Contact information is provided by the study sponsor or research team.

Xavier AYRIGNAC, Medical Doctor

CONTACT

[email protected]

+33 4 67 33 74 13

Sponsors and collaborators

Lead sponsor

University Hospital, Montpellier

Other

Registry information

Acronym: DESIRE MS

Important dates

Study start
2026
Primary completion
2031
Study completion
2031
First posted
Sep 23, 2025
Registry last updated
Jun 23, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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