Azathioprine in MOGAD (MOGwAI)

Civil Hospices of Lyon

Status and phase: Enrolling; Phase 3

Conditions: Central Nervous System Inflammation; MOG-IgG Associated Disease

Treatments: Drug: Azathioprine; Other: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05349006

69HCL21_1065

Details and patient eligibility

About

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.

Enrollment: 126 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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126 participants in 2 patient groups, including a placebo group

Azathioprine

Experimental group

Description:

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)

Treatment:

Drug: Azathioprine

Placebo

Placebo Comparator group

Description:

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)

Treatment:

Other: Placebo