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Recruiting Phase 3

Immediate Versus Delayed Treatment With Azathioprine or Rituximab in Anti-MOG Antibodies Associated Acute Demyelinating Syndromes in Children: a Randomized Controlled Clinical Trial

NCT05545384 · tracked via the Priya Life Science France tracker
Phase
Phase 3
Started
2025-06-23
Last updated
2026-08-31

Condition(s) studied

Acute Demyelinating SyndromeMyelin Oligodendrocyte Glycoprotein Antibody-associated Disease

Investigational drug(s) / intervention(s)

Immediate Azathioprine (1st attack)Immediate Rituximab (1st attack)Standard of care

Immediate Azathioprine (1st attack): Patients randomized in Immediate Azathioprine group will benefit from immediate treatment with azathioprine. Treatment will be started at 2mg/kg or at 1mg/kg if the patient has a partial activity which would be increased slowly according the 6-TGN activity and clinical and biological tolerance at Week 2 for patient with partial activity or M1 for patient without TPMT activity deficit. Only for patient with partial deficit and whose 6-TGN activity is low, azathioprine would be increased at 3mg/kg/d at Week 6 and without exceeding a total daily dose of 150 mg.

Immediate Rituximab (1st attack): Patients randomized in Immediate Rituximab group will benefit from immediate treatment with rituximab. Rituximab 375mg/m2 IV will be given at D1 and D15 and repeat every 6 months for 2 years. Once the inclusion criteria are validated, the first injection will be performed according to the injection protocol (Annex 4). Fifteen day later, the second injection will be performed. The next visit during a consultation with PI or his collaborators will be scheduled 1 week ± 2 days later, and patients will be advised to contact the PI if any neurologic symptoms or symptoms of adverse event occurs in the meantime.

Standard of care: Patients in this group will be treated according to standard care

Study summary

Among all non viral encephalitis, myelin oligodendrocytes glycoprotein antibody associated diseases (MOGAD) are the second most frequent diagnosis in children. Risk of relapses varies according to studied cohorts and cognitive and academic difficulties are more and more detected in children without knowing if these sequelae are related to the first attack or relapses. The hypothesis is that earlier treatment would induce reduction of sequelae after the first attack and the number of relapses which would be also associated with a subsequent reduction of disability occurrence on the long term.

Eligibility

Sex
ALL
Min age
6 Years
Max age
17 Years
Healthy volunteers
No
Inclusion Criteria: * Children \< 18 years old and ≥ 6 years old at baseline * Children weight ≥ 20 kg * All ADS with confirmed anti-MOG-Abs at onset including any acute neurologic symptom with a duration of more than 24H of inflammatory causes (including optic neuritis, transverse myelitis, rhombencephalitis, ADEM, NMOSD) Without any previous treatment other than steroids * Informed consent signed by both parents and the child * Expanded Disability Status Scale (EDSS) \< 5.5 * Affiliated to French social security regime Exclusion Criteria: * Current infection with SARS-COV2 (positive PCR) * Any prior allergy to azathioprine or rituximab with hypersensitivity to active substances, murine proteins or to any of the excipients. * Any prior history of uncontrolled cancer during the last 2 years * Uncontrolled infections (Hepatitis B, C and HIV) * Any prior history of cardiac dysfunction and/or hypertension * Any progressive or non-relapsing form demyelinating diseases * Any previous treatment with natalizumab, daclizumab, fingolimod, methotrexate, cyclosporine, mycophenolate mofetil, rituximab in the last 6 months, or determined by the treating physician to have residual immune suppression from these or other immunosuppressive treatments * CD4+, CD8+, or CD19+ absolute cell count, wbc, neutrophiles in blood at screening below lower limits of normal (LLN) * Creatinine\>30µmol/L * Platelets \<70 000mm3 * Haemoglobin \< 8g/dL * Acute renal insufficiency (clearance \< 30 ml/min) * Prior documented history of hemostase perturbation (TP and/or TCA more than twice of the witnesse's TP and/or TCA) * Prior documented history of increased liver enzyme level (ASAT and/or ALAT) \> 2N. * TP \<70% * Total bilirubin \> 2N * Any patient with allopurinol treatment and immunosupressive treatment with concomitant use of xanthine oxidase inhibitors (e.g. allopurinol, oxipurinol/thiopurinol, febuxostat) * Patients with two inactive TPMT or NUDT15 alleles (homozygous deficient or double heterozygote) * Pregnancy or lactating woman or wish for future pregnancy * Refusal to have a highly effective contraception during traitment and for one year (12 months) after the end of the experimental treatment * participation to another interventional study within 5 half-lives prior to baseline. * Active, severe infections (including tuberculosis, HBV and HCV, HIV, herpes, VZV, EBV and CMV) * Psychosis not controlled by treatment * Patients with Lesch Nyhan syndrome * Pheochromocytoma * Scleroderma * Untreated peptic ulcer * Myasthenia gravis * Any other medical illness or disability that, in the opinion of the investigator, would compromise effective trial participation

Primary outcome measure(s)

  • annualized relapse rate (ARR) at 24 months — at 24 months
    To compare the efficacy of immediate (at first attack) azathioprine (AZA) or rituximab (RTX) treatment in children with MOG antibodies positive diseases with delayed treatment (at second attack), on the annualized relapse rate at 24 months.

Trial sites (9)

FacilityCityRegionStatus
CHU Besançon Besançon France Not Yet Recruiting
CHU Bordeaux Bordeaux France Not Yet Recruiting
CHU Brest Brest France Not Yet Recruiting
HCL de Bron Bron France Not Yet Recruiting
Hôpital Bicêtre Le Kremlin-Bicêtre France Recruiting
CHRU Lille Lille France Not Yet Recruiting
CHU Monptellier Montpellier France Not Yet Recruiting
CHU Strasbourg Strasbourg France Not Yet Recruiting
CHU Toulouse Purpan Toulouse France Not Yet Recruiting
Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05545384 on ClinicalTrials.gov ↗ ← All trials in France