Azathioprine in MOGAD
- Conditions
- Central Nervous System InflammationMOG-IgG Associated Disease
- Interventions
- Other: Placebo
- Registration Number
- NCT05349006
- Lead Sponsor
- Hospices Civils de Lyon
- Brief Summary
MOG-IgG associated disease (MOGAD) is a rare inflammatory disease of the central nervous system recently described. Initially reported as monophasic, data from incident cohorts suggests that around 50% of adult patients with MOG-Ab may relapse within the first two years of the disease, with most of relapses occurring early after disease onset.
No randomized controlled trial has ever been performed and therapeutic guidelines for this disease remain unclear especially after a single event. In short-sized and mainly retrospective study, azathioprine, an immunosuppressant drug, have showed promising results on preventing the risk of relapse in MOGAD patients.
The hypothesis is that the initiation of a treatment after a first attack of MOGAD should prevent further relapse and disability accrual. The investigators propose herein the first randomized controlled trial in MOGAD, to evaluate the efficacy of azathioprine to prevent relapses, after a first attack, in a placebo double-blinded design.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 126
- Age ≥ 18 years
- First attack of documented acute demyelinating syndrome of the central nervous system, within the past 3 months, whatever the severity or the clinical phenotype
- Tested positive for MOG-Ab, confirmed in a centralized lab (Lyon referral centre)
- Ability of the subject to understand the purpose and risks of the study and provide signed and dated written informed consent.
- Patients should be beneficiary of health care coverage under the social security system
- Female patients of childbearing potential should have effective contraception throughout the course of treatment and for at least three months after stopping treatment.
- Hypersensitivity to azathioprine or steroids
- Active infections or cancer (including tuberculosis, hepatitis, herpes and VZV)
- Psychosis not controlled by treatment
- Seriously impaired bone marrow functions: Lymphocyte count < 1000/ml and or Polynuclear neutrophil count < 1500/ml
- Seriously impaired hepatic functions: ALT and/or AST > 3N
- Seriously impaired renal functions: GFR < 29 ml/min/1.73m²
- Any live vaccine in the past 3 months or planned during the RCT and RCT+6months
- Thiopurine methyltransferase (TPMT) phenotype deficient or intermediate, with enzymatic activity < 16 nmol/h/ml
- Unable to complete an MRI (e.g. due to pacemaker, severe claustrophobia, hypersensitivity to contrast media, or who lack adequate peripheral venous access)
- Necessary use of a xanthine oxidase inhibitor (Allopurinol, Oxipurinol, Thiopurinol, Febuxotat,...)
- Necessary use of angiotensin-converting-enzyme inhibitor, cotrimoxazole, cimetidine and indometacine
- Necessary use of an aminosalicylate derivates
- Necessary use of any another immunosuppressive therapy, different than azathioprine, or steroids
- Necessary use of cytotoxic therapy
- Necessary use of any other medical illness or disability that, in the opinion of the investigator, would compromise effective trial participation
- Current enrollment or a plan to enroll in any interventional clinical study in which an investigational treatment or approved therapy is use within 5 half-lives prior to baseline. Participation in a non- interventional study can be allowed as long as this participation does not interfere with this protocol or is not likely to affect the subject's ability to comply with the protocol.
- For subjects coming back from strongyloidiasis endemic regions, a parasitology screening examination will be performed on faeces, and that appropriate treatment will be performed prior to administration of corticosteroids
- Patients with Lesch Nyhan syndrome
- Asian patients (probable mutation of the gene NUDT1)
- Female subjects who have a positive a positive urinary or blood pregnancy test result, are pregnant or are currently breast feeding
- Inability to comply with study requirements
- Person under legal protection or deprived of liberty
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Azathioprine Azathioprine Azathioprine, dose related to weight (100 mg for weight ≤ 50 kg and 150 mg for weight \> 50 kg), oral, daily Associated to oral corticosteroid, prednisone : 40 mg per day during three months, and progressively tapered during three months until stop (- 30 mg during 15 days, 20mg during 15 days, 15 mg during 15 days, 10 mg during 15 days, 5 mg during 15 days and introduction of hydrocortisone 20 mg + Stop prednisone; hydrocortisone 20mg during 15 days, Stop hydrocortisone) Placebo Placebo Placebo, once a day, oral, number of caps related to weight Associated to oral corticosteroid: prednisone 40 mg per day during three months and progressively tapered during three months until stop (- 30 mg during 15 days, 20mg during 15 days, 15 mg during 15 days, 10 mg during 15 days, 5 mg during 15 days and introduction of hydrocortisone 20 mg + Stop prednisone; hydrocortisone 20mg during 15 days, Stop hydrocortisone)
- Primary Outcome Measures
Name Time Method Time to first relapse (in days), comparing azathioprine-treated vs placebo-treated patients during a randomized control period of a maximum of three years. During a randomized control period of a maximum of three years A definite relapse will be defined as such:
* When a patient is diagnosed as experiencing a relapse by the local investigator, the anonymized file will be reviewed within 4 days by a second investigator neurologist, not aware of the randomization group nor of the center treating the patient.
* If this second neurologist also considers the patient as experiencing a relapse, the patient will be considered as relapsing for the main analysis.
* If the second neurologist disagrees, the opinion of a third neurologist will be asked and the majority opinion will be retained.
As to ensure a maximum of homogeneity, we also propose a protocol-defined criteria for a MOGAD relapse, validated by the steering committee and available to every investigator (see Annex 2).
- Secondary Outcome Measures
Name Time Method Number and type of adverse events, including serious adverse events, related to azathioprine and/or steroids and placebo : During a randomized control period of a maximum of three years Evaluation of global disability at 36 months at baseline and at 36 months Worsening from baseline to 36 months of the Ambulation Score.
Evaluation of visual disability at 36 months at baseline and at 36 months Worsening from baseline to 36 months of the peripapillary retinal nerve fiber layer thickness (μm) and the ganglion cell complex thickness (μm) assessed with spectral domain OCT (each eye tested separately).
Quality of life will be assessed using the EuroQOL EQ-5D-3L at 36 months at 36 months https://euroqol.org
Compliance to treatment During a randomized control period of a maximum of three years percentage of untaken pills (left in the blisters) regarding each patient
Exploratory radiological features at baseline and at 36 months Description and comparison between the two groups of worsening of MRI (brain and/or spinal cord and/or visual) from baseline to 36 months assessed by number of new T1 gadolinium enhancing lesions
Exploratory biological features at screening, at 6 months, at 12 months, at 36 months and in case of a relapse In each group of treatment, prognostic value of longitudinal MOG-Ab-titers to predict relapse.
Trial Locations
- Locations (17)
Department of Neurology, CHU de Bordeaux - GH Pellegrin
🇫🇷Bordeaux, France
Department of Neurology, CHU of Lille, Hospital Roger Salengro
🇫🇷Lille, France
Department of Neuro Ophthalmology, CHU of Lyon, Neurology Hospital Pierre Wertheimer
🇫🇷Lyon, France
Service de Neurologie sclérose en plaques, pathologies de la myéline et neuro-inflammation - Centre de référence des maladies inflammatoires rares du cerveau et de la moelle (MIRCEM) - Hôpital Neurologique Pierre Wertheimer - Hospices Civils de Lyon
🇫🇷Lyon, France
Department of Neurology University hospital Timone
🇫🇷Marseille, France
Department of Neurology Montpellier Universitary Hospital
🇫🇷Montpellier, France
CHRU de Nancy Hôpital Central
🇫🇷Nancy, France
Department of Neurology, Hôpital Pasteur 2
🇫🇷Nice, France
Department of Neurology, Hôpital Caremeau
🇫🇷Nîmes, France
National Hospital of Vision (15-20)
🇫🇷Paris, France
Department of Neurology APHP, Pitié Salpêtrière Hospital
🇫🇷Paris, France
Department of Neurology. Hôpital A. Fondation Rothschild
🇫🇷Paris, France
Department of Neurology, CHU de Rennes
🇫🇷Rennes, France
Department of Neurology, CHU de Rouen
🇫🇷Rouen, France
Department of Neurology, Hôpital g. Et r. Laennec
🇫🇷Saint-Herblain, France
Department of Neurology, Hôpital Hautepierre
🇫🇷Strasbourg, France
Department of Neurology, Toulouse Universitary Hospital
🇫🇷Toulouse, France