myelin oligodendrocytes glycoprotein antibody associated diseases (MOGAD)
Conditions
Interventions
Trade Name: IMUREL 25 mg
Product Name: azathioprine
Pharmaceutical Form: Coated tablet
INN or Proposed INN: Azathioprine
CAS Number: 446-86-6
Concentration unit: mg milligram(s)
Concentration type: e
Sponsors
Assistance Publique – Hôpitaux de Paris (AP-HP)
Eligibility
Sex/Gender
All
Inclusion 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) =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Current infection with SARS-COV2 (positive PCR) - Any prior allergy to azathioprine or rituximab - Any prior history of uncontrolleduncontrolled 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 2 X witnesses - Prior documented history of increased liver enzyme level (ASAT and/or ALAT) > 2N. - TP 2N - Any patient with allopurinol treatment and immunosupressive treatment - Patients with two inactive TPMT alleles (homozygous deficient or double heterozygote) - Pregnancy or lactating woman or wish for future pregnancy - Refusal to have a double effective contraception during the follow-up and until one year (12 months) after the end of the experimental treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: -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. -The primary endpoint will be the annualized relapse rate (ARR) at 24 months. ;Secondary Objective: •To compare the efficacy between azathioprine (AZA) and rituximab (RTX) in immediate (at first attack) treatment in children with MOGAD •To compare separately the efficacy between immediate-AZA with dealayed-treatment and immediate-RTX with delayed treatment •Evaluate the efficacy of immediate treatment with delayed treatment on other clinical outcomes: oAnnualized relapse rate at 12 months oTime to first relapse after the first attack oPercentage of patients free of relapses over 24 months oMotor disability outcome oCognitive outcome oVisual outcome oFatigue oDepression oQuality of life •Evaluate the efficacy on MRI outcomes •Evaluate the efficacy through modulation of immunological mechanism between treated and not treated patients •Follow immunological markers of treatment efficacy such as neurofilament (Nfl) •Verify the safety and tolerance of the treatment ;Primary end point(s): -Analysis of primary endpoint will be based on intent-to-treat analysis. The primary endpoint will be the annualized relapse rate (ARR) at 24 months. ;Timepoint(s) of evaluation of this end point: 24 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints are other clinical, imaging, immunological and biological outcome and tolerance and safety of treatment. • Comparison between immediate-AZA and immediate- RTX - Annualized relapse rate at 12 and 24 months • Comparison between immediate-AZA and delayed-treatment - Annualized relapse rate at 12 and 24 months • Comparison between immediate-RTX and delayed-treatment - Annualized relapse rate at 12 and 24 months • Other clinical outcome for comparing immediate- and delayed-treatment - Annualized relapse rate at 12 months - Time to first relapse (2nd attack) will be defined as time from randomization to the date of first relapse, with right-censoring in case of loss of follow-up - Percentage of patients free of relapses over 24 months - Motor disability outcome will be assessed with Expanded Disability Status Scale (EDSS) score (see section 18.5.1) every 6 months which is a frequently used score in pediatric MS for neurological disability40-42. The EDSS is an ordinal scale used for assessing neurologic impairment based on a neurological examination. It consists of scores in each of seven central functional systems (FSs) that are then combined to determine the EDSS steps (ranging from 0 (normal) to 10 (death due to MS)). The FSs are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel & Bladder, and Cerebral functions. EDSS is a widely used and accepted instrument to evaluate disability status at a given time and, longitudinally, to assess disability progression in clinical studies in MS other MOG-Abs-ADS related studies. - Visual Acuity, Optical Coherence Tomography (OCT) at 3, 6, 12 and 24 months performed by a pediatric ophthalmologist. - Cognitive function: Wechsler Intelligence Scale for Children (WISC)-V for children more than 6 years at 6 months of randomization and at 2 years43 would be performed by a neuropsychologist - Fatigue: Fatigue Severity Scale (FSS) every 6 months43, this is an auto-questionnaire with | — |
Countries
France
Outcome results
None listed