Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruiting
Participants planned
86
Countries
1
Sites
9
myelin oligodendrocytes glycoprotein antibody associated diseases (MOGAD)
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.
Key facts
- Sponsor
- Assistance Publique Hopitaux De Paris, Assistance Publique Hopitaux De Paris, Assistance Publique Hopitaux De Paris
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Nervous System Diseases [C10]
- Trial duration
- 23 Jun 2025 → ongoing
- Decision date (initial)
- 2024-10-24
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- No
- Funding sources
- DGOS (Direction Générale de l'Offre de Soins), Ministry of Health, France
External identifiers
- EU CT number
- 2024-516243-81-00
- EudraCT number
- 2022-002385-32
- ClinicalTrials.gov
- NCT05545384
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy
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.
Secondary objectives 7
- 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 delayed-treatment and immediate-RTX with delayed treatment
- Evaluate the efficacy of immediate treatment with delayed treatment on other clinical outcomes:
- 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, tau and GFAP).
- Verify the safety and tolerance of the treatment
Conditions and MedDRA coding
myelin oligodendrocytes glycoprotein antibody associated diseases (MOGAD)
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 24.1 | PT | 10085806 | Myelin oligodendrocyte glycoprotein antibody-associated disease | 100000004852 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | IDAR Immediate versus delayed treatment with azathioprine or rituximab in anti-myelin oligodendrocytes glycoprotein (anti-MOG) antibodies associated acute demyelinating syndromes in children: a randomized controlled clinical trial
|
Randomised Controlled | None | Oral azathioprine: 1 to 3 mg/kg/day to maximum daily dose of 150 mg Rituximab 375mg/m2 IV: (day 1 and at Day 15) and every 6 months during 24 months SoC: methylprednisolone 30 mg/kg/day (max 1g/day): will be given for 3 days followed by an oral therapy of prednisolone (or prednisone, only in case of shortage) 1mg/kg/d (max 60 mg/day) during 4 weeks then 0,5mg/kg during 4 weeks in all children, which will be tapered slowly during the next 4 weeks. |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- 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
- Affiliated to French social security regime
Exclusion criteria 16
- 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>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
- Any patient with allopurinol treatment and immunosupressive treatment with concomitant use of xanthine oxidase inhibitors (e.g. allopurinol, oxipurinol/thiopurinol, febuxostat)
- Pregnancy or lactating woman or wish for future pregnancy
- Refusal to have a highly effective contraception during traitment and for one year
- 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.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The primary endpoint will be the annualized relapse rate (ARR) at 24 months.
Secondary endpoints 6
- Comparison between immediate-AZA and immediate - 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 delayedtreatment
- Radiological outcome
- Immunological studies
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 3
SUB05647MIG · Substance
- Active substance
- Azathioprine
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 150 mg milligram(s)
- Max total dose
- 108000 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB05647MIG · Substance
- Active substance
- Azathioprine
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 150 mg milligram(s)
- Max total dose
- 108000 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB12570MIG · Substance
- Active substance
- Rituximab
- Pharmaceutical form
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 375 mg/m2 milligram(s)/square meter
- Max total dose
- 3750 mg/m2 milligram(s)/square meter
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 3
SUB08872MIG · Substance
- Active substance
- Methylprednisolone
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 1 g gram(s)
- Max total dose
- 3 g gram(s)
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB10018MIG · Substance
- Active substance
- Prednisolone
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 60 mg milligram(s)
- Max total dose
- 5040 mg milligram(s)
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB10020MIG · Substance
- Active substance
- Prednisone
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 60 mg milligram(s)
- Max total dose
- 5040 mg milligram(s)
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Assistance Publique Hopitaux De Paris
- Sponsor organisation
- Assistance Publique Hopitaux De Paris
- Address
- Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux
- City
- Paris Cedex 10
- Postcode
- 75475
- Country
- France
Scientific contact point
- Organisation
- Assistance Publique Hopitaux De Paris
- Contact name
- DEIVA
Public contact point
- Organisation
- Assistance Publique Hopitaux De Paris
- Contact name
- Malika Yahmi
Assistance Publique Hopitaux De Paris
- Sponsor organisation
- Assistance Publique Hopitaux De Paris
- Address
- 1 Avenue Claude Vellefaux
- City
- Paris
- Postcode
- 75010
- Country
- France
Assistance Publique Hopitaux De Paris
- Sponsor organisation
- Assistance Publique Hopitaux De Paris
- Address
- 1 Avenue Claude Vellefaux
- City
- Paris
- Postcode
- 75010
- Country
- France
Locations
1 EU/EEA country · 9 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Ongoing, recruiting | 86 | 9 |
| Rest of world | — | 0 | — |
Investigational sites
Assistance Publique Hopitaux De Paris
PEDIATRIC NEUROLOGY, 78 Rue Du General Leclerc, 94270, Le Kremlin-Bicetre
Hospices Civils De Lyon
Paediatrics neurology, 59 Boulevard Pinel, 69500, Bron
CHU Besancon
Pediatrics neurology, 3 Boulevard Alexander Fleming, Cs 81816, Besancon Cedex
Centre Hospitalier Universitaire De Bordeaux
pediatric neurologist, Place Amelie Raba Leon, 33000, Bordeaux
Centre Hospitalier Regional Et Universitaire De Brest
Pediatrics neurology, 5 Avenue Marechal Foch, Bp 824, Brest Cedex 2
Centre Hospitalier Universitaire De Lille
Pediatrics neurology, Avenue Du Professeur Emile Laine, 59037, Lille Cedex
Centre Hospitalier Universitaire De Montpellier
Pediatrics neurology, 371 Avenue Du Doyen Gaston Giraud, 34090, Montpellier
Les Hopitaux Universitaires De Strasbourg
Pediatrics neurology, 1 Avenue Moliere, Bp 49, Strasbourg Cedex 2
Centre Hospitalier Universitaire De Toulouse
Pediatrics - Neurology and infectiologyinfectiology, 330 Avenue De Grande Bretagne, 31059, Toulouse Cedex 9
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| France | 2025-06-23 | 2025-06-23 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 13 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_2024-516243-81-00_V4-1_20240806_IDAR_for publication | 4-1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1 |
| Subject information and informed consent form (for publication) | L1_SIS-ICF_NI-12-18ans_V1-1_20220803 | 1-1 |
| Subject information and informed consent form (for publication) | L1_SIS-ICF_NI-6-11ans_V1-2_20220808 | 1-2 |
| Subject information and informed consent form (for publication) | L1_SIS-ICF_nifc_RI_autorite-parentale_V2-0_20230601 | 2-0 |
| Subject information and informed consent form (for publication) | L1_SIS-ICF_nifc_RI_patient devenu majeur_V2-0_20230601 | 2-0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_AZATHIOPRINE50 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_IMUREL25 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_methylprednisolone_500mg | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_prednisolone | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Prednisone | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Rixathon | 1 |
| Synopsis of the protocol (for publication) | D1_Resume_2024-516243-81-00_V4-1_20240806_IDAR | 4-1 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-10-10 | France | Acceptable 2024-10-24
|
2024-10-24 |