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

• Status: Not yet recruiting
• Trial end date: 2026-11-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborator: Institut National de la Santé Et de la Recherche Médicale, France
• Treatments: Azathioprine; Rituximab

Criteria

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