Recruiting

NCT Number: NCT06342544

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

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.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Ocular Myasthenia Gravis Autoimmune Diseases Autoimmune Diseases of the Nervous System Immune System Diseases Myasthenia Gravis Neoplasms Neoplasms by Site Nervous System Diseases Nervous System Neoplasms Neurodegenerative Diseases Neuromuscular Diseases Neuromuscular Junction Diseases Paraneoplastic Syndromes Paraneoplastic Syndromes, Nervous System

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Centre Hospitalier Universitaire De Bordeaux, Bordeaux, France

Who can participate

Healthy volunteers accepted: No

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

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

Treatment and study plan

immediate treatment with corticosteroids

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

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.

Primary outcomes

proportion of patients who progressed to generalized myasthenia within 2 years of follow-up

Time frame: Day0 to month24

Generalization is defined by a loss of 5 points or more on any Myasthenic Muscle Score (MMS) item, excluding "eyelid occlusion" and "extrinsic ocular musculature".

Progress towards generalization will be assessed by an expert physician, blinded to the intervention arm.

Study contacts

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

Antoine Gueguen

CONTACT

[email protected]

+33148036852

Sponsors and collaborators

Lead sponsor

Fondation Ophtalmologique Adolphe de Rothschild

Network

Registry information

Acronym: IMCOMG

Important dates

Study start: 2025
Primary completion: 2028
Study completion: 2029
First posted: Apr 2, 2024
Registry last updated: Jan 21, 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.

Published trials that share one or more normalized conditions with this study.

Recruiting