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Trial record 2 of 2 for:    MOGAD

Azathioprine in MOGAD (MOGwAI)

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ClinicalTrials.gov Identifier: NCT05349006
Recruitment Status : Not yet recruiting
First Posted : April 27, 2022
Last Update Posted : November 28, 2022
Sponsor:
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Central Nervous System Inflammation MOG-IgG Associated Disease Drug: Azathioprine Other: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 126 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: double blind
Primary Purpose: Treatment
Official Title: A Randomized, Placebo-controlled Phase 3 Trial of Azathioprine for the Prevention of Relapse in Myelin-oligodendrocyte-glycoprotein (MOG)-Antibody Associated Disease
Estimated Study Start Date : January 1, 2023
Estimated Primary Completion Date : January 1, 2026
Estimated Study Completion Date : January 1, 2029


Arm Intervention/treatment
Experimental: Azathioprine

Azathioprine, dose related to weight (100 mg for <50 kg, 150 mg 50-100 kg, 200 mg for >100 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
Dose related to weigh (100 mg for <50 kg, 150 mg 50-100 kg, 200 mg for >100 kg) = 2 to 4 50mg oral caps, daily, during all the study period

Placebo Comparator: 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)

Other: Placebo
Dose related to weigh (100 mg for <50 kg, 150 mg 50-100 kg, 200 mg for >100 kg) = 2 to 4 50mg oral caps, daily, during all the study period




Primary Outcome Measures :
  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. [ Time Frame: 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 :
  1. Number and type of adverse events, including serious adverse events, related to azathioprine and/or steroids and placebo [ Time Frame: : During a randomized control period of a maximum of three years ]
  2. Evaluation of global disability at 36 months [ Time Frame: at baseline and at 36 months ]
    Global disability at 36 months assessed by EDSS: The EDSS scale is a method of quantifying disability and monitoring changes in the level of disability over time. It is widely used in clinical trials and in the assessment of patients with inflammatory disorders of the central nervous system. The EDSS scale ranges from 0 to 10 in 0.5-unit increments (20 values) that represent higher levels of disability. Scoring is based on an examination by a neurologist.

  3. Evaluation of global disability at 36 months [ Time Frame: at baseline and at 36 months ]
    Worsening from baseline to 36 months of the EDSS

  4. Evaluation of global disability at 36 months [ Time Frame: at baseline and at 36 months ]
    Ambulation status at 36 months assessed by the Ambulation Score. Scoring is based on a measurement of the distance the patient is able to walk (in meters) and then classified in 12 levels.

  5. Evaluation of global disability at 36 months [ Time Frame: at baseline and at 36 months ]
    Worsening from baseline to 36 months of the Ambulation Score.

  6. Evaluation of visual disability at 36 months [ Time Frame: at baseline and at 36 months ]
    Best-corrected high contrast visual acuity at 36 months measured (each eye tested separately) using the standard Snellen chart or equivalent.

  7. Evaluation of visual disability at 36 months [ Time Frame: at baseline and at 36 months ]
    Worsening from baseline to 36 months of visual disability assessed by change of the best- corrected high-contrast visual acuity using the standard Snellen chart or equivalent (each eye tested separately).

  8. Evaluation of visual disability at 36 months [ Time Frame: at baseline and at 36 months ]
    Best-corrected low-contrast visual acuity at 36 months using the Sloan Charts at 2.5%, in each eye.

  9. Evaluation of visual disability at 36 months [ Time Frame: at baseline and at 36 months ]
    Worsening from baseline to 36 months of low-contrast visual acuity using the Sloan Charts at 2.5%, in each eye.

  10. Evaluation of visual disability at 36 months [ Time Frame: at baseline and at 36 months ]
    Inner retinal layers thicknesses at 36 months assessed by the spectral domain OCT (each eye tested separately)

  11. Evaluation of visual disability at 36 months [ Time Frame: 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).

  12. Quality of life will be assessed using the EuroQOL EQ-5D-3L at 36 months [ Time Frame: at 36 months ]
    https://euroqol.org

  13. Compliance to treatment [ Time Frame: During a randomized control period of a maximum of three years ]
    percentage of untaken pills (left in the blisters) regarding each patient

  14. Exploratory radiological features [ Time Frame: at baseline and at 36 months ]
    Description, and comparison between the two groups, of worsening of MRI (brain and spinal cord and visual) from baseline to 36 months assessed by number of new/enlarging T2 lesions

  15. Exploratory radiological features [ Time Frame: 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

  16. Exploratory biological features [ Time Frame: at screening, at 6 months, at 12 months, at 36 months and in case of a relapse ]
    In each group of treatment, association between MOG-Ab titer at first episode and the risk of relapse

  17. Exploratory biological features [ Time Frame: at screening, at 6 months, at 12 months, at 36 months and in case of a relapse ]
    In each group of treatment, association between MOG-Ab titer at onset and the level of global disability assessed by the EDSS at 36 months.

  18. Exploratory biological features [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Exclusion Criteria:

  • Hypersensitivity to azathioprine or steroids
  • Active infections or cancer
  • Seriously impaired hepatic or bone marrow functions:

Lymphocyte count < 1000/ml and or Polynuclear neutrophil count < 1500/ml ALT and/or AST > 3N

  • Any live vaccine in the past 3 months
  • 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 allopurinol and febuxostat
  • Necessary use of any another immunosuppressive therapy different than azathioprine or steroids
  • Current enrollment or a plan to enroll in any interventional clinical study in which an investigational treatment or approved therapy is use. 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.
  • Female subjects who have a positive blood pregnancy test result, are pregnant or are currently breast feeding. All female subjects of childbearing potential must practice effective contraception during the study.
  • Inability to comply with study requirements
  • Vulnerable patients (defined by articles L1121-5 to L1121-8 and L1122-1-2 from French Public Health Code)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05349006


Contacts
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Contact: Romain MARIGNIER, MD PhD +334 72 35 75 22 romain.marignier@chu-lyon.fr
Contact: Lakhdar BENYAHYA, project manager +334 72 68 49 07 lakhdar.benyahya@chu-lyon.fr

Locations
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France
Department of Neurology, CHU de Bordeaux - GH Pellegrin
Bordeaux, France
Contact: Aurélie RUET, Pr    +33 (0)5 56 79 55 21    aurelie.ruet@chu-bordeaux.fr   
Department of Neurology, CHU of Lille, Hospital Roger Salengro
Lille, France
Contact: Helene ZEPHIR, Pr    +33 (0)3 20 44 68 46    thi-helene.zephir@chru-lille.fr   
Department of Neuro Ophthalmology, CHU of Lyon, Neurology Hospital Pierre Wertheimer
Lyon, France
Contact: Caroline FROMENT, Pr    +33 (0)472118012    caroline.froment01@chu-lyon.fr   
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
Contact: Romain MARIGNIER, Pr    +33 4 72 35 75 22    romain.marignier@chu-lyon.fr   
Department of Neurology University hospital Timone
Marseille, France
Contact: Bertrand AUDOIN, Pr    +33 (0)4 91 38 59 39    bertrand.audoin@ap-hm.fr   
Department of Neurology Montpellier Universitary Hospital
Montpellier, France
Contact: Xavier AYRIGNAC, Dr    +33 (0)4 67 33 94 69    x-ayrignac@chu-montpellier.fr   
Department of Neurology, Hôpital Pasteur 2
Nice, France
Contact: Mikael COHEN, Dr    +33 (0)4 92 03 98 93    cohen.m@chu-nice.fr   
Department of Neurology, Hôpital Caremeau
Nîmes, France
Contact: Eric THOUVENOT, Pr    +33 (0)4 66 68 32 61    eric.thouvenot@chu-nimes.fr   
Department of Neurology APHP, Pitié Salpêtrière Hospital
Paris, France
Contact: Elisabeth MAILLART, Dr    +33 (0)1 42 16 19 75    elisabeth.maillart@aphp.fr   
Department of Neurology. Hôpital A. Fondation Rothschild
Paris, France
Contact: Romain DESCHAMPS, Dr    +33 (0)1 48 03 68 52    rdeschamps@for.paris   
Department of Neurology, CHU de Rennes
Rennes, France
Contact: Laure MICHEL, Dr    +33 (0)2 99 28 98 42    laure.michel@chu-rennes.fr   
Department of Neurology, CHU de Rouen
Rouen, France
Contact: Bertrand BOURRE, Dr    +33 (0)2 32 88 67 49    bertrand.bourre@chu-rouen.fr   
Department of Neurology, Hôpital g. Et r. Laennec
Saint-Herblain, France
Contact: David LAPLAUD, Pr    +33 (0)2 40 16 52 12    david.laplaud@chu-nantes.fr   
Department of Neurology, Hôpital Hautepierre
Strasbourg, France
Contact: Nicolas COLLONGUES, Dr    +33 (0)88 12 85 44    nicolas.collongues@chru-strasbourg.fr   
Department of Neurology, Toulouse Universitary Hospital
Toulouse, France
Contact: Jonathan CIRON, Dr    +33 (0)5 61 77 91 06    ciron.j@chu-toulouse.fr   
Sponsors and Collaborators
Hospices Civils de Lyon
Investigators
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Study Director: Romain MARIGNIER, MD PhD Hospices Civils de Lyon
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Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT05349006    
Other Study ID Numbers: 69HCL21_1065
First Posted: April 27, 2022    Key Record Dates
Last Update Posted: November 28, 2022
Last Verified: April 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hospices Civils de Lyon:
MOGAD
azathioprine
optic neuritis
myelitis
neuromyelitis optica
MOG-IgG associated disease
Additional relevant MeSH terms:
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Inflammation
Pathologic Processes
Azathioprine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents