Azathioprine in MOGAD

NCT05349006 | Recruiting Phase 3 DMC

• 1 other identifier: 69HCL21_1065
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 17

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.

Conditions

Central Nervous System Inflammation; MOG-IgG Associated Disease

Keywords

MOGAD; azathioprine; optic neuritis; myelitis; neuromyelitis optica; MOG-IgG associated disease

Outcome Measures

Primary Outcomes (1)

• Time to first relapse (in days), comparing azathioprine-treated vs placebo-treated patients 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).

  During a randomized control period of a maximum of three years

Secondary Outcomes (18)

• 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

• Evaluation of global disability at 36 months

  at baseline and at 36 months

• Evaluation of global disability at 36 months

  at baseline and at 36 months

• Evaluation of global disability at 36 months

  at baseline and at 36 months

Study Arms (2)

Azathioprine

EXPERIMENTAL

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)

Drug: Azathioprine

Placebo

PLACEBO COMPARATOR

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)

Other: Placebo

Interventions

Azathioprine DRUG

Dose related to weigh (100 mg for weight ≤ 50 kg and 150 mg for weight \> 50 kg) = 2 to 4 50mg oral caps, daily, during all the study period

Azathioprine

Placebo OTHER

Dose related to weigh (100 mg for weight ≤ 50 kg and 150 mg for weight \> 50 kg) = 2 to 4 50mg oral caps, daily, during all the study period

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (17)

Department of Neurology, CHU de Bordeaux - GH Pellegrin

Bordeaux, France

RECRUITING

Department of Neurology, CHU of Lille, Hospital Roger Salengro

Lille, France

RECRUITING

Department of Neuro Ophthalmology, CHU of Lyon, Neurology Hospital Pierre Wertheimer

Lyon, France

RECRUITING

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

RECRUITING

Department of Neurology University hospital Timone

Marseille, France

RECRUITING

Department of Neurology Montpellier Universitary Hospital

Montpellier, France

RECRUITING

CHRU de Nancy Hôpital Central

Nancy, 54035, France

RECRUITING

Department of Neurology, Hôpital Pasteur 2

Nice, France

NOT YET RECRUITING

Department of Neurology, Hôpital Caremeau

Nîmes, France

RECRUITING

National Hospital of Vision (15-20)

Paris, 75012, France

RECRUITING

Department of Neurology APHP, Pitié Salpêtrière Hospital

Paris, France

RECRUITING

Department of Neurology. Hôpital A. Fondation Rothschild

Paris, France

RECRUITING

Department of Neurology, CHU de Rennes

Rennes, France

RECRUITING

Department of Neurology, CHU de Rouen

Rouen, France

RECRUITING

Department of Neurology, Hôpital g. Et r. Laennec

Saint-Herblain, France

RECRUITING

Department of Neurology, Hôpital Hautepierre

Strasbourg, France

RECRUITING

Department of Neurology, Toulouse Universitary Hospital

Toulouse, France

RECRUITING

MeSH Terms

Conditions

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease; Optic Neuritis; Myelitis; Neuromyelitis Optica

Interventions

Azathioprine

Condition Hierarchy (Ancestors)

Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Immune System Diseases; Optic Nerve Diseases; Cranial Nerve Diseases; Nervous System Diseases; Eye Diseases; Central Nervous System Infections; Infections; Central Nervous System Diseases; Spinal Cord Diseases; Neuroinflammatory Diseases; Myelitis, Transverse; Demyelinating Autoimmune Diseases, CNS; Demyelinating Diseases

Intervention Hierarchy (Ancestors)

Thionucleosides; Sulfur Compounds; Organic Chemicals; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Romain MARIGNIER, MD PhD

  Hospices Civils de Lyon

  STUDY DIRECTOR

Central Study Contacts

Romain MARIGNIER, MD PhD

CONTACT

+334 72 35 75 22; romain.marignier@chu-lyon.fr

Lakhdar BENYAHYA, project manager

CONTACT

+334 72 68 49 07; lakhdar.benyahya@chu-lyon.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2022
• First Posted: April 27, 2022
• Study Start: December 12, 2023
• Primary Completion (Estimated): December 12, 2026
• Study Completion (Estimated): December 12, 2029
• Last Updated: February 4, 2025

Record last verified: 2025-01

Locations

FR (17)