search
Back to results

Azathioprine in MOGAD (MOGwAI)

Primary Purpose

Central Nervous System Inflammation, MOG-IgG Associated Disease

Status
Not yet recruiting
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Azathioprine
Placebo
Sponsored by
Hospices Civils de Lyon
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Central Nervous System Inflammation focused on measuring MOGAD, azathioprine, optic neuritis, myelitis, neuromyelitis optica, MOG-IgG associated disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

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)

Sites / Locations

  • Department of Neurology, CHU de Bordeaux - GH Pellegrin
  • Department of Neurology, CHU of Lille, Hospital Roger Salengro
  • Department of Neuro Ophthalmology, CHU of Lyon, Neurology Hospital Pierre Wertheimer
  • 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
  • Department of Neurology University hospital Timone
  • Department of Neurology Montpellier Universitary Hospital
  • Department of Neurology, Hôpital Pasteur 2
  • Department of Neurology, Hôpital Caremeau
  • Department of Neurology APHP, Pitié Salpêtrière Hospital
  • Department of Neurology. Hôpital A. Fondation Rothschild
  • Department of Neurology, CHU de Rennes
  • Department of Neurology, CHU de Rouen
  • Department of Neurology, Hôpital g. Et r. Laennec
  • Department of Neurology, Hôpital Hautepierre
  • Department of Neurology, Toulouse Universitary Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Azathioprine

Placebo

Arm Description

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)

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)

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Number and type of adverse events, including serious adverse events, related to azathioprine and/or steroids and placebo
Evaluation of global disability 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.
Evaluation of global disability at 36 months
Worsening from baseline to 36 months of the EDSS
Evaluation of global disability 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.
Evaluation of global disability at 36 months
Worsening from baseline to 36 months of the Ambulation Score.
Evaluation of visual disability at 36 months
Best-corrected high contrast visual acuity at 36 months measured (each eye tested separately) using the standard Snellen chart or equivalent.
Evaluation of visual disability 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).
Evaluation of visual disability at 36 months
Best-corrected low-contrast visual acuity at 36 months using the Sloan Charts at 2.5%, in each eye.
Evaluation of visual disability at 36 months
Worsening from baseline to 36 months of low-contrast visual acuity using the Sloan Charts at 2.5%, in each eye.
Evaluation of visual disability at 36 months
Inner retinal layers thicknesses at 36 months assessed by the spectral domain OCT (each eye tested separately)
Evaluation of visual disability 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
https://euroqol.org
Compliance to treatment
percentage of untaken pills (left in the blisters) regarding each patient
Exploratory radiological features
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
Exploratory radiological features
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
In each group of treatment, association between MOG-Ab titer at first episode and the risk of relapse
Exploratory biological features
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.
Exploratory biological features
In each group of treatment, prognostic value of longitudinal MOG-Ab-titers to predict relapse.

Full Information

First Posted
April 15, 2022
Last Updated
November 24, 2022
Sponsor
Hospices Civils de Lyon
search

1. Study Identification

Unique Protocol Identification Number
NCT05349006
Brief Title
Azathioprine in MOGAD
Acronym
MOGwAI
Official Title
A Randomized, Placebo-controlled Phase 3 Trial of Azathioprine for the Prevention of Relapse in Myelin-oligodendrocyte-glycoprotein (MOG)-Antibody Associated Disease
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
January 1, 2023 (Anticipated)
Primary Completion Date
January 1, 2026 (Anticipated)
Study Completion Date
January 1, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Central Nervous System Inflammation, MOG-IgG Associated Disease
Keywords
MOGAD, azathioprine, optic neuritis, myelitis, neuromyelitis optica, MOG-IgG associated disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
double blind
Allocation
Randomized
Enrollment
126 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Azathioprine
Arm Type
Experimental
Arm Description
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)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm 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)
Intervention Type
Drug
Intervention Name(s)
Azathioprine
Intervention Description
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
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
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 Measure Information:
Title
Time to first relapse (in days), comparing azathioprine-treated vs placebo-treated patients during a randomized control period of a maximum of three years.
Description
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).
Time Frame
During a randomized control period of a maximum of three years
Secondary Outcome Measure Information:
Title
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
Title
Evaluation of global disability at 36 months
Description
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.
Time Frame
at baseline and at 36 months
Title
Evaluation of global disability at 36 months
Description
Worsening from baseline to 36 months of the EDSS
Time Frame
at baseline and at 36 months
Title
Evaluation of global disability at 36 months
Description
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.
Time Frame
at baseline and at 36 months
Title
Evaluation of global disability at 36 months
Description
Worsening from baseline to 36 months of the Ambulation Score.
Time Frame
at baseline and at 36 months
Title
Evaluation of visual disability at 36 months
Description
Best-corrected high contrast visual acuity at 36 months measured (each eye tested separately) using the standard Snellen chart or equivalent.
Time Frame
at baseline and at 36 months
Title
Evaluation of visual disability at 36 months
Description
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).
Time Frame
at baseline and at 36 months
Title
Evaluation of visual disability at 36 months
Description
Best-corrected low-contrast visual acuity at 36 months using the Sloan Charts at 2.5%, in each eye.
Time Frame
at baseline and at 36 months
Title
Evaluation of visual disability at 36 months
Description
Worsening from baseline to 36 months of low-contrast visual acuity using the Sloan Charts at 2.5%, in each eye.
Time Frame
at baseline and at 36 months
Title
Evaluation of visual disability at 36 months
Description
Inner retinal layers thicknesses at 36 months assessed by the spectral domain OCT (each eye tested separately)
Time Frame
at baseline and at 36 months
Title
Evaluation of visual disability at 36 months
Description
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).
Time Frame
at baseline and at 36 months
Title
Quality of life will be assessed using the EuroQOL EQ-5D-3L at 36 months
Description
https://euroqol.org
Time Frame
at 36 months
Title
Compliance to treatment
Description
percentage of untaken pills (left in the blisters) regarding each patient
Time Frame
During a randomized control period of a maximum of three years
Title
Exploratory radiological features
Description
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
Time Frame
at baseline and at 36 months
Title
Exploratory radiological features
Description
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
Time Frame
at baseline and at 36 months
Title
Exploratory biological features
Description
In each group of treatment, association between MOG-Ab titer at first episode and the risk of relapse
Time Frame
at screening, at 6 months, at 12 months, at 36 months and in case of a relapse
Title
Exploratory biological features
Description
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.
Time Frame
at screening, at 6 months, at 12 months, at 36 months and in case of a relapse
Title
Exploratory biological features
Description
In each group of treatment, prognostic value of longitudinal MOG-Ab-titers to predict relapse.
Time Frame
at screening, at 6 months, at 12 months, at 36 months and in case of a relapse

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Romain MARIGNIER, MD PhD
Phone
+334 72 35 75 22
Email
romain.marignier@chu-lyon.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Lakhdar BENYAHYA, project manager
Phone
+334 72 68 49 07
Email
lakhdar.benyahya@chu-lyon.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Romain MARIGNIER, MD PhD
Organizational Affiliation
Hospices Civils de Lyon
Official's Role
Study Director
Facility Information:
Facility Name
Department of Neurology, CHU de Bordeaux - GH Pellegrin
City
Bordeaux
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aurélie RUET, Pr
Phone
+33 (0)5 56 79 55 21
Email
aurelie.ruet@chu-bordeaux.fr
Facility Name
Department of Neurology, CHU of Lille, Hospital Roger Salengro
City
Lille
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Helene ZEPHIR, Pr
Phone
+33 (0)3 20 44 68 46
Email
thi-helene.zephir@chru-lille.fr
Facility Name
Department of Neuro Ophthalmology, CHU of Lyon, Neurology Hospital Pierre Wertheimer
City
Lyon
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Caroline FROMENT, Pr
Phone
+33 (0)472118012
Email
caroline.froment01@chu-lyon.fr
Facility Name
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
City
Lyon
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Romain MARIGNIER, Pr
Phone
+33 4 72 35 75 22
Email
romain.marignier@chu-lyon.fr
Facility Name
Department of Neurology University hospital Timone
City
Marseille
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bertrand AUDOIN, Pr
Phone
+33 (0)4 91 38 59 39
Email
bertrand.audoin@ap-hm.fr
Facility Name
Department of Neurology Montpellier Universitary Hospital
City
Montpellier
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xavier AYRIGNAC, Dr
Phone
+33 (0)4 67 33 94 69
Email
x-ayrignac@chu-montpellier.fr
Facility Name
Department of Neurology, Hôpital Pasteur 2
City
Nice
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mikael COHEN, Dr
Phone
+33 (0)4 92 03 98 93
Email
cohen.m@chu-nice.fr
Facility Name
Department of Neurology, Hôpital Caremeau
City
Nîmes
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eric THOUVENOT, Pr
Phone
+33 (0)4 66 68 32 61
Email
eric.thouvenot@chu-nimes.fr
Facility Name
Department of Neurology APHP, Pitié Salpêtrière Hospital
City
Paris
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elisabeth MAILLART, Dr
Phone
+33 (0)1 42 16 19 75
Email
elisabeth.maillart@aphp.fr
Facility Name
Department of Neurology. Hôpital A. Fondation Rothschild
City
Paris
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Romain DESCHAMPS, Dr
Phone
+33 (0)1 48 03 68 52
Email
rdeschamps@for.paris
Facility Name
Department of Neurology, CHU de Rennes
City
Rennes
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Laure MICHEL, Dr
Phone
+33 (0)2 99 28 98 42
Email
laure.michel@chu-rennes.fr
Facility Name
Department of Neurology, CHU de Rouen
City
Rouen
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bertrand BOURRE, Dr
Phone
+33 (0)2 32 88 67 49
Email
bertrand.bourre@chu-rouen.fr
Facility Name
Department of Neurology, Hôpital g. Et r. Laennec
City
Saint-Herblain
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David LAPLAUD, Pr
Phone
+33 (0)2 40 16 52 12
Email
david.laplaud@chu-nantes.fr
Facility Name
Department of Neurology, Hôpital Hautepierre
City
Strasbourg
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nicolas COLLONGUES, Dr
Phone
+33 (0)88 12 85 44
Email
nicolas.collongues@chru-strasbourg.fr
Facility Name
Department of Neurology, Toulouse Universitary Hospital
City
Toulouse
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jonathan CIRON, Dr
Phone
+33 (0)5 61 77 91 06
Email
ciron.j@chu-toulouse.fr

12. IPD Sharing Statement

Learn more about this trial

Azathioprine in MOGAD

We'll reach out to this number within 24 hrs