AZATHIOPRINE for Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)

Inclusion criteria

• {"criterion_text":"- Children <18 years old and ≥ 6 years old at baseline\n- Children weight ≥ 20 kg\n- 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\n- Informed consent signed by both parents and the child\n- Expanded Disability Status Scale (EDSS) < 5.5 Affiliated to French social security regime\n- Affiliated to French social security regime"}

Exclusion criteria

• {"criterion_text":"- Current infection with SARS-COV2 (positive PCR)\n- Any patient with allopurinol treatment and immunosupressive treatment with concomitant use of xanthine oxidase inhibitors (e.g. allopurinol, oxipurinol/thiopurinol, febuxostat)\n- Pregnancy or lactating woman or wish for future pregnancy\n- Refusal to have a highly effective contraception during traitment and for one year\n- participation to another interventional study within 5 half-lives prior to baseline.\n- Active, severe infections (including tuberculosis, HBV and HCV, HIV, herpes, VZV, EBV and CMV)\n- Psychosis not controlled by treatment - Patients with Lesch Nyhan syndrome - Pheochromocytoma - Scleroderma - Untreated peptic ulcer - Myasthenia gravis\n- Any other medical illness or disability that, in the opinion of the investigator, would compromise effective trial participation.\n- Any prior allergy to azathioprine or rituximab with hypersensitivity to active substances, murine proteins or to any of the excipients.\n- Any prior history of uncontrolled cancer during the last 2 years\n- Uncontrolled infections (Hepatitis B, C and HIV)\n- Any prior history of cardiac dysfunction and/or hypertension\n- Any progressive or non-relapsing form demyelinating diseases\n- 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\n- CD4+, CD8+, or CD19+ absolute cell count, wbc, neutrophiles in blood at screening below lower limits of normal (LLN)\n- Creatinine>80μmol/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"}

Primary endpoints

• {"endpoint_text":"- The primary endpoint will be the annualized relapse rate (ARR) at 24 months.","definition_or_measurement_approach":"Annualized relapse rate (ARR) measured at 24 months (compare ARR between immediate AZA/RTX treatment and delayed treatment at 24 months)."}

Secondary endpoints

• {"endpoint_text":"- Comparison between immediate-AZA and immediate - Annualized relapse rate at 12 and 24 months\n- Comparison between immediate-AZA and delayed-treatment - Annualized relapse rate at 12 and 24 months\n- Comparison between immediate-RTX and delayed-treatment - Annualized relapse rate at 12 and 24 months\n- Other clinical outcome for comparing immediate- and delayedtreatment\n- Radiological outcome\n- Immunological studies","definition_or_measurement_approach":"Secondary endpoints include ARR at 12 and 24 months for specified comparisons; other clinical outcomes (not further defined in provided data); radiological outcomes (MRI measures); immunological studies (e.g., biomarkers such as neurofilament, tau, GFAP) as listed in secondary objectives."}

France

Earliest CTIS Part Ii Submission Date

31-08-2024

Latest Decision Or Authorization Date

24-10-2024

Processing Time Days

54

Number Of Sites

9

Number Of Participants

86

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"France","full_name":"DGOS (Direction Générale de l'Offre de Soins), Ministry of Health, France","duties_or_roles":"Funding / monetary support","organisation_type":"Government / Ministry of Health"}