Impact of Annual Versus Biannual Infusions of Ocrelizumab in Patients With Active MS,After 2 Years of Initial Treatment, on Freedom From Radiological Disease Activity at Two Years: a Multicenter Randomized Controlled Non-inferiority Trial

NCT ID: NCT05999604

Last Updated: 2026-01-21

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

244 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-11-09

Study Completion Date

2029-11-30

Brief Summary

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Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system and the leading cause of severe non-traumatic disability in young people, affecting 110,000 people in France. Ocrelizumab, a humanized anti-CD20 monoclonal antibody, has shown remarkable efficacy in Phase III trials on the inflammatory component of the disease, reducing the annualized relapse rate by 46% and the rate of new T2 lesions by 80% compared with interferon-β 1a.

The use of anti-CD20 agents, including ocrelizumab, is associated with an infectious risk that increases with duration of exposure, part of which is due to the development of hypo-gammaglobulinemia in relation to cumulative dose.

Several reports suggest a persistent effect of anti-CD20 drugs in MS, with no resumption of inflammatory activity after discontinuation:

* During the development of ocrelizumab, at the end of phase 2, after having received 3 or 4 semi-annual cycles of ocrelizumab, a safety period with a therapeutic window of 18 months was planned, before re-administration in the extension study. During this therapeutic window, the annualized relapse rate remained stable, and patients showed no radiological disease activity.
* Scandinavian observational studies of "off-label" use of anti-CD20 in MS provide real-life evidence of the absence of recovery of clinical and radiological activity after prolonged interruption of treatment.

After 2 years of treatment, and with disease activity under control, spacing administration intervals could reduce the risk of infection without reducing treatment efficacy. This would facilitate the decision to maintain highly active immunotherapy over the long term. In addition, this therapeutic de-escalation, by reducing the frequency of infusions and associated day hospitalizations, would help to reduce treatment management costs.

Our aim is to evaluate the non-inferiority of 12-monthly spacing of ocrelizumab infusions versus the conventional 6-monthly regimen, in a population of active MS patients over 18 years of age who have already received 4 or more semi-annual cycles of treatment for 2 years.

Detailed Description

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Conditions

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Multiple Sclerosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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annual ocrelizumab infusions

Group Type EXPERIMENTAL

Ocrelizumab Injection [Ocrevus]

Intervention Type DRUG

Annual administration

semestrial ocrelizumab infusions

Group Type OTHER

Ocrelizumab Injection [Ocrevus]

Intervention Type DRUG

Semestrial administration

Interventions

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Ocrelizumab Injection [Ocrevus]

Semestrial administration

Intervention Type DRUG

Ocrelizumab Injection [Ocrevus]

Annual administration

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Patient 18 years of age or older
2. Presenting for a 4th semi-annual cycle of ocrelizumab (minimum)
3. Requires follow-up MRI as part of treatment.
4. Initial indication for ocrelizumab according to the marketing authorization (active MS, RR or SP form)
5. Absence of relapse for at least 18 months (a relapse being defined as the appearance of new symptoms or worsening of existing symptoms, lasting more than 24 hours and outside a period of fever or an infectious episode; notified as a validated relapse by the neurologist in the patient's file, treated or not with boluses of Solu-Medrol).
6. EDSS between 0 and 6 inclusive
7. Having received informed information about the study and having signed a consent to participate in the study
8. French language proficiency
9. Affiliated or beneficiary of a social insurance scheme

Exclusion Criteria

1. Clinical forms of primary progressive MS
2. Patients already receiving systematically spaced doses of ocrelizumab ≥ 9 months apart
3. Contraindication to continued treatment with ocrelizumab (hypersensitivity reaction, ongoing active infection, development of malignancy since previous injection, development of severe immune deficiency)
4. Planned pregnancy within 3 years
5. Contraindication to MRI
6. Contraindication to injection of contrast media
7. Subject with severe or uncontrolled symptoms of renal, hepatic, hematological, gastrointestinal, pulmonary, psychiatric or cardiac disease, or any uncontrolled intercurrent pathology.
8. Patient under legal protection
9. Patients of childbearing age who do not wish to use effective contraception
10. Pregnant or breast-feeding women
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fondation Ophtalmologique Adolphe de Rothschild

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Hôpital Henri Mondor

Créteil, , France

Site Status RECRUITING

CH Gonesse

Gonesse, , France

Site Status RECRUITING

CHU de Grenoble

Grenoble, , France

Site Status RECRUITING

CHU de Limoges

Limoges, , France

Site Status RECRUITING

Hôpital Pierre Wertheimer (HCL)

Lyon, , France

Site Status RECRUITING

CHU de Nice

Nice, , France

Site Status RECRUITING

Hôpital de la Pitié-Salpêtrière

Paris, , France

Site Status RECRUITING

Fondation Adolphe de Rothschild

Paris, , France

Site Status RECRUITING

CHI Poissy-Saint-Germain en Laye

Poissy, , France

Site Status RECRUITING

CHU de Strasbourg

Strasbourg, , France

Site Status RECRUITING

Hôpital Foch

Suresnes, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Dr Caroline Bensa

Role: CONTACT

+33 148036753

Dr Amélie Yavchitz

Role: CONTACT

Facility Contacts

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Pr Alain Créange

Role: primary

+33 149812315

Dr Eric Manchon

Role: primary

+33 134535532

Dr Olivier Casez

Role: primary

+33 4 76 76 75 75

Dr Alexis Montcuquet

Role: primary

+33 555056561

Pr Sandra Vukusic

Role: primary

+33 472681313

Dr Mikaël Cohen

Role: primary

+33 492039893

Dr Elisabeth Maillart

Role: primary

+33 142161975

Dr Caroline BENSA

Role: primary

+33 148036753

Dr Olivier Heinzlef

Role: primary

+33 139274181

Pr Jérôme De Seze

Role: primary

+33 388128544

Dr Maia Tchikviladze

Role: primary

+33 146251185

Other Identifiers

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CBR_2022_13

Identifier Type: -

Identifier Source: org_study_id

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