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

Sponsor
Assistance Publique - Hôpitaux de Paris
Study ID
NCT05545384
Phase
PHASE3
Status
Recruiting
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Conditions

  • Acute Demyelinating Syndrome

Eligibility Criteria

Sex
ALL
Age
6 Years - 17 Years
Healthy Volunteers
Not accepted

Interventions

  • Immediate Azathioprine (1st attack) — DRUG
    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) — DRUG
    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 — DRUG
    Patients in this group will be treated according to standard care

Study Details

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.

Key Dates

Start date
Apr 30, 2025
Status verified
Mar 2025
Primary completion
Apr 30, 2027
Completion
Apr 30, 2030

Study Design

Enrollment
86 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Immediate Azathioprine (1st attack)
    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.
  • Experimental: Immediate Rituximab (1st attack)
    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.
  • Active Comparator: Standard Care: delayed treatment (2nd attack)
    Patients will be treated according to standard of care after their 1st attack. In case of relapse: * before 3 months, IV methylprednisolone (30 mg/kg/j not exceeding 1g/day) will be administered for 3 days. There won't be any change of the initial treatment which will be pursued. * after 3 months, IV methylprednisolone (30 mg/kg/j not exceeding 1g/day) will be administered for 3 days with an oral relay of prednisolone (1mg/kg/day not exceeding 60 mg/day) during 3 months with then a slowly tapered dose (reduction of 25% every week for 4 weeks). Azathioprine or Rituximab might be proposed as per local clinician experience

Primary Outcome Measure

annualized relapse rate (ARR) at 24 months [ Time Frame: at 24 months ]

Central Contacts