Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruiting
Participants planned
126
Countries
1
Sites
17
neurology
The primary endpoint is the time to first relapse, comparing azathioprine-treated vs placebo-treated patients during a randomized control period of a maximum of three years.
Key facts
- Sponsor
- Hospices Civils De Lyon
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Nervous System Diseases [C10]
- Trial duration
- 1 Mar 2023 → ongoing
- Decision date (initial)
- 2022-10-10
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- No
- Funding sources
- DGOS
External identifiers
- EU CT number
- 2022-500520-30-00
- ClinicalTrials.gov
- NCT05349006
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
The primary endpoint is the time to first relapse, comparing azathioprine-treated vs placebo-treated patients during a randomized control period of a maximum of three years.
Secondary objectives 5
- To assess the tolerability and safety of azathioprine in an adult MOGAD population
- To assess the prevention of accrual of global disability in MOGAD, at 3 years, by the use of azathioprine in comparison to placebo
- To assess the prevention of accrual of visual disability in MOGAD, at 3 years, by the use of azathioprine in comparison to placebo
- To compare the quality of life at 3 years, between azathioprine and control group
- To assess compliance to treatment
Conditions and MedDRA coding
neurology
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | PT | 10078318 | Anti-myelin-associated glycoprotein antibodies positive | 100000004848 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Azathioprine/ Placebo This trial is a randomized controlled superiority trial in two parallel arms against placebo.
|
Randomised Controlled | Double | [{"id":89187,"code":4,"name":"Analyst"},{"id":89189,"code":1,"name":"Subject"},{"id":89190,"code":3,"name":"Monitor"},{"id":89188,"code":2,"name":"Investigator"}] | 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) 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) |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- 1. Age ≥ 18 years
- 2. First attack of documented acute demyelinating syndrome of the central nervous system, within the past 3 months, whatever the severity or the clinical phenotype
- 3. Tested positive for MOG-Ab, confirmed in a centralized lab (Lyon referral center)
- Capacity of the subject to understand the purpose and risks of the study and provide signed and dated written informed consent.
- 5. Patients should be beneficiary of health care coverage under the social security system
- 6. 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 17
- 1. Hypersensitivity to azathioprine or steroids
- 2. Active infections or cancer
- 3. Seriously impaired bone marrow functions: Lymphocyte count < 1000/ml and or Polynuclear neutrophil count < 1500/ml
- 4. Seriously impaired hepatic functions: ALT and/or AST > 3N
- 5. Seriously impaired renal functions: GFR < 29 ml/min/1.73m²
- 6. Any live vaccine in the past 3 months
- 7. Thiopurine methyltransferase (TPMT) phenotype deficient or intermediate, with enzymatic activity < 16 nmol/h/ml
- 8. Unable to complete an MRI (e.g. due to pacemaker, severe claustrophobia, hypersensitivity to contrast media, or who lack adequate peripheral venous access)
- 9. Necessary use of a xanthine oxidase inhibitor (Allopurinol, Oxipurinol, Thiopurinol, Febuxotat,…)
- 10. Necessary use of angiotensin-converting-enzyme inhibitor, cotrimoxazole, cimetidine and indometacine
- 11. Necessary use of an aminosalicylate derivates
- 12. Necessary use of any another immunosuppressive therapy, different than azathioprine, or steroids
- 13. Necessary use of cytotoxic therapy
- 14. 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.
- 15. Female subjects who have a positive blood pregnancy test result, are pregnant or are currently breast feeding
- 16. Inability to comply with study requirements
- 17. Person under legal protection or deprived of liberty
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The primary endpoint is the time to first relapse, comparing azathioprine-treated vs placebo-treated patients during a randomized control period of a maximum of three years.
Secondary endpoints 5
- Number and type of adverse events, including serious adverse events, related to azathioprine and/or steroids.
- • Global disability at M36 assessed by EDSS (Expanded Disability Status Scale) • Worsening from baseline to M36 of the EDSS • Ambulation status at M36 assessed by the Ambulation Score based on a measurement of the distance the patient is able to walk. • Worsening from baseline to M36 of the Ambulation Score.
- • Best-corrected high contrast visual acuity at M36 measured using the standard Snellen chart or equivalent. • Worsening from baseline to M36 of visual disability assessed by change of the best- corrected high-contrast visual acuity using the standard Snellen chart or equivalent. • Best-corrected low-contrast visual acuity at M36 using the Sloan Charts at 2.5%, in each eye. • Worsening from baseline to M36 of low-contrast visual acuity using the Sloan Charts at 2.5%, in each eye. • Inner retina
- Quality of life will be assessed using the EuroQOL EQ-5D-3L at M36
- Compliance to treatment will be described in both arms by the percentage of untaken tablets (left in the blisters) regarding each patient’s time of participation in the study.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
SCP276432 · ATC
- Active substance
- Azathioprine
- Route of administration
- ORAL USE
- Max daily dose
- 100 mg milligram(s)
- Max total dose
- 200 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AX01 — AZATHIOPRINE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- il n'est pas utilisé dans l'indication
Placebo 1
Hydrogénophosphate de calcium dihydraté : Fournisseur Brenntag
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Auxiliary 2
SCP132446 · ATC
- Active substance
- Prednisolone
- Substance synonyms
- (8S,9S,10S,11S,13S,14S,17R)-11,17-DIHYDROXY-17-(2-HYDROXYACETYL)-10,13-DIMETHYL-7,8,9,11,12,14,15,16-OCTAHYDRO-6H-CYCLOPENTA[A]PHENANTHREN-3-ONE, GLPG0303, DELTA-HYDROCORTISONE, 1,2-DEHYDROHYDROCORTISONE, METACORTANDRALONE
- Route of administration
- ORAL USE
- Max daily dose
- 40 mg milligram(s)
- Max total dose
- 600 mg milligram(s)
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- H02AB07 — PREDNISONE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Il n'est pas utilisé dans l'indication
SCP29190199 · ATC
- Active substance
- Hydrocortisone
- Substance synonyms
- CORTISOL
- Route of administration
- ORAL USE
- Max daily dose
- 20 mg milligram(s)
- Max total dose
- 40 mg milligram(s)
- Max treatment duration
- 1 Month(s)
- Authorisation status
- Authorised
- ATC code
- H02AB09 — HYDROCORTISONE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- il n'est pas utilisé dans l' indication
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Hospices Civils De Lyon
- Sponsor organisation
- Hospices Civils De Lyon
- Address
- 3 Quai Des Celestins, Bp 2251 Bp 2251
- City
- Lyon Cedex 02
- Postcode
- 69229
- Country
- France
Scientific contact point
- Organisation
- Hospices Civils De Lyon
- Contact name
- Pr Marignier
Public contact point
- Organisation
- Hospices Civils De Lyon
- Contact name
- Pr Marignier
Locations
1 EU/EEA country · 17 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Ongoing, recruiting | 126 | 17 |
| Rest of world | — | 0 | — |
Investigational sites
Assistance Publique Hopitaux De Paris
Department of Neurology, Num Voie 47 A 83, 47 Boulevard De L Hopital, Paris
Hôpital de Hautepierre
Department of Neurology, 1 avenue Moliere, 67200, Strasbourg
Timone University Hospital
Department of Neurology, 265 Rue Saint Pierre, 13005, Marseille
Hopital Fondation Adolphe De Rothschild
Department of Neurology, 25 Rue Manin, 75019, Paris
Centre Hospitalier Universitaire De Nantes
Department of Neurology, Boulevard Du Professeur Jacques Monod, 44800, Saint Herblain
Hopital Purpan
Department of Neurology, Place Du Docteur Joseph Baylac, 31000, Toulouse
Hospices Civils De Lyon
Department of Neuro Ophthalmology, 59 Boulevard Pinel, 69677, Bron Cedex
CHRU Lille - Hopital Roger Salengro
Department of Neurology, Avenue Du Professeur Emile Laine, 59037, Lille Cedex
Centre Hospitalier Universitaire De Nimes
Department of Neurology, 4 Place Du Professeur Robert Debre, 30029, Nimes Cedex 9
CHRU De Nancy
Department of Neurology, Co N°34, 29 Avenue Du Mal De Lattre De Tassigny, Nancy Cedex
Hospital Pasteur
Department of Neurology, 30 Voie Romaine, Cs 61069, Nice Cedex 1
CHU De Rennes
Department of Neurology, 2 Rue Henri Le Guilloux, 35033, Rennes Cedex 9
Quinze-Vingts National Ophthalmology Hospital
Medecine Interne, 28 Rue De Charenton, 75012, Paris
CHU De Rouen
Department of Neurology, 1 Rue De Germont, 76031, Rouen Cedex
Hospices Civils De Lyon
Service de Neurologie sclérose en plaques, pathologies de la myéline et neuro-inflammation, 59 Boulevard Pinel, 69677, Bron Cedex
Centre Hospitalier Universitaire De Bordeaux
Department of Neurology, 1 Place Amelie Raba Leon, Cs 91286, Bordeaux Cedex
Centre Hospitalier Universitaire De Montpellier
Department of Neurology, 80 Avenue Augustin Fliche, 34295, Montpellier Cedex 5
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| France | 2023-03-01 | 2023-12-12 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 10 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2022-500520-30-00 redacted | 5 |
| Recruitment arrangements (for publication) | Document additionnel | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1 |
| Subject information and informed consent form (for publication) | 2022-500520-30-00 ICF v4 | 4 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF description | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF description | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF description v3 | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF description v5 | 5 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Azathioprine_TEVA | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis 2022-500520-30-00 redacted | 6 |
Application history
4 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2022-06-28 | France | Acceptable 2022-10-10
|
2022-10-10 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2022-11-08 | France | Acceptable | 2022-12-02 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-05-17 | France | Acceptable 2024-06-18
|
2024-07-09 |
| 4 | SUBSTANTIAL MODIFICATION | SM-4 | 2024-10-08 | France | Acceptable 2024-11-12
|
2024-12-09 |