Immediate Corticosteroid Therapy and Rituximab to Prevent Generalization in Ocular Myasthenia: a PROBE Multicenter Open-label Randomized Controlled Trial.

NCT ID: NCT06342544

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

128 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-04-29

Study Completion Date

2029-06-30

Brief Summary

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Myasthenia is an autoimmune disease causing dysfunction of the neuromuscular junction, resulting in fluctuating and variable muscle weakness.

In the initial phase of the disease, 70% of patients present with ocular onset myasthenia (OMG), i.e. weakness limited to the oculomotor muscles. Generalization to skeletal, bulbar and axial muscles occurs in 20-40% of cases, with a higher frequency in the first and second years, respectively 46% and 60% of generalizations. This reflects the maturation of the autoimmune response in the early years of the disease, and represents a therapeutic window of opportunity to modify the course of the disease.

Generalization is a critical event, putting the patient at risk of admission to an intensive care unit and necessitating the use of long-term immunosuppressants.

There is currently no validated strategy for preventing generalization. On the one hand, a preventive role for corticosteroid therapy in ocular-onset myasthenia has been observed in some studies, but not confirmed by others. These contradictory results may be explained by the bias of retrospective observational studies and the use of different corticosteroid administration regimens.

On the other hand, recent data on the use of low-dose Rituximab in the early phase of the disease shows greater efficacy than later use, enabling prolonged remission of the disease with a very good tolerability profile.

We propose to compare in a randomized controlled trial the usual practice with a proactive strategy with a standardized corticosteroid regimen immediate at diagnosis.

Patients with ocular myasthenia are usually treated symptomatically with acetylcholinesterase inhibitors. The introduction of corticosteroids is delayed and limited to patients with persistent disabling diplopia or ptosis with occlusion. When corticosteroids are tapered off, ocular symptoms may recur. This level of corticosteroid dependence observed in patients treated for ocular myasthenia has not been specifically studied. In order to reduce the levels of corticosteroids administered and avoid recurrence of ocular symptoms and their delayed generalization, it is usually proposed to introduce another immunosuppressant.

The aim of this study is to evaluate the efficacy of a standardized proactive prevention strategy on the generalization of ocular onset myasthenias during the first 2 years. It will combine immediate treatment with corticosteroids at the time of diagnosis, with the addition of rituximab in the event of recurrence of ocular symptoms as corticosteroids are tapered off.

Detailed Description

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Conditions

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Ocular Myasthenia Gravis

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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immediate treatment with corticosteroids addition of rituximab if recurrence

Group Type EXPERIMENTAL

immediate treatment with corticosteroids

Intervention Type DRUG

Immediate standardized treatment with corticosteroids. Standardized treatment in the experimental arm will start at 0.5mg/kg/d prednisone.

addition of rituximab if recurrence

Intervention Type DRUG

rituximab added if ocular symptoms reappear as corticosteroids are tapered off. Rituximab will be given at a dose of 500mg/6months for 12 months.

based on standard practice

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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immediate treatment with corticosteroids

Immediate standardized treatment with corticosteroids. Standardized treatment in the experimental arm will start at 0.5mg/kg/d prednisone.

Intervention Type DRUG

addition of rituximab if recurrence

rituximab added if ocular symptoms reappear as corticosteroids are tapered off. Rituximab will be given at a dose of 500mg/6months for 12 months.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Patients over 18 years of age
* Diagnosis of ocular myasthenia within the last 6 months, defined :

* either by a typical clinical examination objectified by an expert clinician: ptosis and/or binocular diplopia, with a variable and fluctuating character (either spontaneous or provoked by effort or rest)
* or by positive anti-AChR antibodies or the presence of decrement on repetitive nerve stimulation or a positive edrophonium test
* Ocular symptoms lasting at least one month and limited to extra-ocular muscles (weakness in one or both orbicularis oculi)
* No non-ocular symptoms on MMS, MGC and MG-ADL.
* Naïve to immunosuppressive therapy for ocular myasthenia gravis.

Exclusion Criteria

* Thymoma
* Pupillary anomaly other than that resulting from previous local disease or surgery.
* Signs of restrictive abduction or supraduction myopathy due to dysthyroid ophthalmopathy.
* Graves' ophthalmopathy
* Onset of ocular symptoms more than one year before screening date
* Hypersensitivity to rituximab, murine proteins, prednisone, methylprednisone, aziathioprine or 6-mercaptopurine, paracetamol, dexchlorpheniramine.
* Any infectious condition
* Patients with severe immune deficiency
* Severe heart failure (New York Heart Association (NYHA) Class IV) or severe uncontrolled heart disease
* Severe hepatic insufficiency
* Psychotic states not yet controlled by treatment
* Hyperuricemia on xanthine oxidase inhibitors (allopurinol and febuxostat)
* Risk of angle-closure glaucoma
* Risk of urinary retention due to urethro-prostatic disorders
* Vaccination with live attenuated vaccine required during study and up to 6 months after rituximab discontinuation
* Women of childbearing age who do not wish to use effective contraception during their participation and at least 12 months after
* 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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Centre Hospitalier Universitaire De Bordeaux

Bordeaux, , France

Site Status RECRUITING

Hôpital Raymond Pointcarre

Garches, , France

Site Status NOT_YET_RECRUITING

Centre Hospitalier Universitaire De Lille

Lille, , France

Site Status RECRUITING

Hospices Civils De Lyon

Lyon, , France

Site Status RECRUITING

Centre Hospitalier Universitaire De Nice

Nice, , France

Site Status RECRUITING

CHNO

Paris, , France

Site Status ACTIVE_NOT_RECRUITING

Hôpital de la Pitié-Salpêtrière

Paris, , France

Site Status NOT_YET_RECRUITING

Centre Hospitalier Sainte Anne

Paris, , France

Site Status ACTIVE_NOT_RECRUITING

Fondation Adolphe de Rothschild

Paris, , France

Site Status RECRUITING

Les Hopitaux Universitaires De Strasbourg

Strasbourg, , France

Site Status RECRUITING

Centre Hospitalier Universitaire De Toulouse

Toulouse, , France

Site Status ACTIVE_NOT_RECRUITING

Countries

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France

Central Contacts

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Antoine Gueguen

Role: CONTACT

+33148036852

Facility Contacts

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Dr Guilhem Sole

Role: primary

+33557821380

Dr Edouard Berling

Role: primary

+33147107900

Dr Céline Tard

Role: primary

+33320444145

Pr Caroline Froment

Role: primary

+33472118012

Dr Saskia Bresch

Role: primary

+33492038173

Dr Sophie Demeret

Role: primary

+33142161831

Dr Antoine Gueguen

Role: primary

+33148036755

Dr Aleksandra Nadaj-Pakleza

Role: primary

+33388128556

Other Identifiers

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AGN_2023_14

Identifier Type: -

Identifier Source: org_study_id

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