Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Authorised, recruitment pending
Participants planned
250
Countries
1
Sites
27
Multiple sclerosis
To demonstrate the non-inferiority of de-escalation strategy from anti-CD20 therapy to platform therapies versus anti-CD20 maintenance in relapsing remitting MS patients on the % of patients without clinical and/or MRI disease activity between D0 and M36.
Key facts
- Sponsor
- Centre Hospitalier Universitaire De Montpellier
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Nervous System Diseases [C10]
- Decision date (initial)
- 2025-04-28
- Transition trial
- No
- Low-intervention
- Yes
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- DGOS
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy, Therapy
To demonstrate the non-inferiority of de-escalation strategy from anti-CD20 therapy to platform therapies versus anti-CD20 maintenance in relapsing remitting MS patients on the % of patients without clinical and/or MRI disease activity between D0 and M36.
Secondary objectives 17
- To compare percentage of patients without relapse on both groups (de-escalation vs maintenance) from D0 to M36
- To compare percentage of patients without confirmed disability progression (EDSS increase) on both groups (de-escalation vs maintenance) from D0 to M36
- To compare percentage of patients without new/enlarged T2 lesions on both groups (de-escalation vs maintenance) from D0 to M36
- To compare number of adverse events and severe adverse events on both groups (de-escalation vs maintenance) from D0 to M36
- To compare infections and serious infections on both groups (de-escalation vs maintenance) from D0 to M36
- To compare change of B-cells count and serum immunoglobulin levels (IgG, A, M) on both groups (de-escalation vs maintenance) from D0 to M36
- To compare annualized relapse rate on both groups (de-escalation vs maintenance) from D0 to M36
- To compare time to first relapse on both groups (de-escalation vs maintenance) from D0 to M36
- To compare time to disability progression on both groups (de-escalation vs maintenance) from D0 to M36
- To compare brain volume change on both groups (de-escalation vs maintenance) from D0 to M36
- To compare change of serum Neurofilament light chains on both groups (de-escalation vs maintenance) from D0 to M36
- To compare immunoglobulin (IgG, A, M) levels changes on both groups (de-escalation vs maintenance) from D0 to M36
- To compare B-cells repopulation (CD19+/CD20+ B-cells) on both groups (de-escalation vs maintenance) from D0 to M36
- To compare CD27+ memory B-cells repopulation on both groups (de-escalation vs maintenance) from D0 to M36
- To compare patients’ quality of life on both groups (de-escalation vs maintenance) from D0 to M36
- To compare patients’ experience of the quality of care on both groups (de-escalation vs maintenance) from D0 to M36
- To compare medico-economic impact on both groups (de-escalation vs maintenance) from D0 to M36
Conditions and MedDRA coding
Multiple sclerosis
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.1 | PT | 10063399 | Relapsing-remitting multiple sclerosis | 100000004852 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Randomization group Patients will be randomised into two parallel groups (1:1)
|
Randomised Controlled | Single | [{"id":121703,"code":2,"name":"Investigator"}] | Experimental group: Patients randomized in the experimental group will be treated with platform therapies (Dimethyl Fumarate, Diroximel fumarate, Teriflunomide, Glatiramer Acetate, Beta-interferons) according to treatments’ authorization from the day of randomization to M36. Control group: Patients randomized in the control group will be treated every 6 months (or, up to one year, at the same interval dosing) for patients with anti-CD20 (ocrelizumab, rituximab) or every 4 weeks for patients with subcutaneous anti-CD20 (ofatumumab) from the day of randomization to M36. |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 4
- Patients ≥40 years at inclusion
- Patients with relapsing remitting multiple sclerosis at inclusion (according to 2017 McDonald criteria) treated with anti-CD20 for at least the last 3 years. For patients treated with IV ocrelizumab or rituximab at extended interval dosing, a maximum interval of 12 months between perfusions during the year before inclusion visit is required
- No evidence of disease activity for the last 3 years on anti-CD20 (No relapse AND no new/enlarged MRI lesion)
- Brain MRI performed according to OFSEP protocol within a maximum of 6 months before randomization
Exclusion criteria 20
- Secondary or primary progressive MS at inclusion
- Previous experience of treatment failure in patients treated with natalizumab, fingolimod, rituximab, ocrelizumab, mitoxantrone, alemtuzumab or cladribine
- Treatment with high dose corticosteroids during the 30 days preceding inclusion
- Contraindication to MRI
- Severely immunocompromised state
- Current severe active infection
- Known active malignancy
- Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease
- Severe hepatic impairment (Child-Pugh class C)
- Significantly impaired bone marrow function or significant anaemia, leukopenia, neutropenia or thrombocytopenia
- Severe renal impairment undergoing dialysis
- Severe hypoproteinaemia
- Current severe depression and/or suicidal ideation
- Suspected or confirmed progressive multifocal leukoencephalopathy (PML)
- Any condition that, in the opinion of the investigator, would interfere with the interpretation of patient safety or place the patient at high risk for treatment-related complications
- Participation in another therapeutic trial in the last 6 months
- Protected population according to articles of the French Public Health Code (e.g. patients under law protection, prisoners, pregnant, parturient or lactating women, and patients under guardianship/curatorship)
- All women of childbearing age not using effective contraception during the study
- Subjects not covered by public health insurance
- Failure to obtain written informed consent after a reflection period
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The % of patients without disease activity between D0 and M36. Disease activity is defined as 1) the presence of at least one clinical relapse between inclusion and M36 AND/OR 2) Brain MRI activity defined as at least 1 new/enlarged T2/FLAIR lesion on MRI scans between baseline MRI and M36.
Secondary endpoints 13
- Relapses
- Disability
- New/enlarged T2/FLAIR lesions
- Adverse event and severe adverse events
- Infections and serious infections
- B-cells counts
- Serum immunoglobulin levels (IgG, A, M)
- Brain volume
- Neurofilaments light chain values
- EQ5D-5L score
- MUSICARE score
- Incremental cost-utility ratio at year 3
- Annual budget impact from the SNDS (Système National des Données de Santé hosted by French Health Insurance)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 9
SUB188604 · Substance
- Active substance
- Diroximel Fumarate
- Pharmaceutical form
- GASTRO-RESISTANT CAPSULE, HARD
- Route of administration
- ORAL
- Max daily dose
- 924 mg milligram(s)
- Max total dose
- 1011780 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB25218 · Substance
- Active substance
- Teriflunomide
- Pharmaceutical form
- FILM COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 14 mg milligram(s)
- Max total dose
- 15330 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB13608MIG · Substance
- Active substance
- Dimethyl Fumarate
- Pharmaceutical form
- GASTRO-RESISTANT CAPSULE, HARD
- Route of administration
- ORAL
- Max daily dose
- 240 mg milligram(s)
- Max total dose
- 262800 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB13608MIG · Substance
- Active substance
- Dimethyl Fumarate
- Pharmaceutical form
- GASTRO-RESISTANT CAPSULE, HARD
- Route of administration
- ORAL
- Max daily dose
- 480 mg milligram(s)
- Max total dose
- 525600 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB12440MIG · Substance
- Active substance
- Interferon BETA-1A
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 132
- Max total dose
- 144540
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB12440MIG · Substance
- Active substance
- Interferon BETA-1A
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAMUSCULAR INJECTION
- Max daily dose
- 30 µg microgram(s)
- Max total dose
- 4680 µg microgram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB121165 · Substance
- Active substance
- Peginterferon BETA-1A
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 125 µg microgram(s)
- Max total dose
- 9750 µg microgram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB13971MIG · Substance
- Active substance
- Glatiramer Acetate
- Pharmaceutical form
- SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 20 mg/ml milligram(s)/millilitre
- Max total dose
- 21900 mg/ml milligram(s)/millilitre
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB13971MIG · Substance
- Active substance
- Glatiramer Acetate
- Pharmaceutical form
- SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 120 mg milligram(s)
- Max total dose
- 18720 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 3
SUB25221 · Substance
- Active substance
- Ofatumumab
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 20 mg milligram(s)
- Max total dose
- 720 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB12570MIG · Substance
- Active substance
- Rituximab
- Pharmaceutical form
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 1000 mg milligram(s)
- Max total dose
- 6000 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB121707 · Substance
- Active substance
- Ocrelizumab
- Pharmaceutical form
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 600 mg milligram(s)
- Max total dose
- 3600 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Centre Hospitalier Universitaire De Montpellier
- Sponsor organisation
- Centre Hospitalier Universitaire De Montpellier
- Address
- 191 Avenue Du Doyen Gaston Giraud
- City
- Montpellier Cedex 5
- Postcode
- 34295
- Country
- France
Scientific contact point
- Organisation
- Centre Hospitalier Universitaire De Montpellier
- Contact name
- AYRIGNAC Xavier
Public contact point
- Organisation
- Centre Hospitalier Universitaire De Montpellier
- Contact name
- AYRIGNAC Xavier
Locations
1 EU/EEA country · 27 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Authorised, recruitment pending | 250 | 27 |
| Rest of world | — | 0 | — |
Investigational sites
Centre Hospitalier Universitaire De Montpellier
Neurologie, 80 Avenue Augustin Fliche, 34295, Montpellier Cedex 5
Centre Hospitalier Intercommunal De Poissy Saint Germain
Neurologie, Residence Les Maisonnees, 10 Rue Du Champ Gaillard, Poissy
Hospital Foch
Neurologie, 40 Rue Worth, 92150, Suresnes
Centre Hospitalier Universitaire De Nantes
Neurologie, 5 Allee De L Ile Gloriette, Cs 69301, Nantes Cedex 1
Centre Hospitalier Universitaire Grenoble Alpes
Neurologie, Boulevard De La Chantourne, 38700, La Tronche
Centre Hospitalier Universitaire Rouen
Neurologie, 1 Rue De Germont, Bp 96031, Rouen Cedex
Centre Hospitalier Universitaire De Bordeaux
Neurologie, Place Amelie Raba Leon, 33000, Bordeaux
Centre Hospitalier Universitaire De Nice
Neurologie, 30 Voie Romaine, 06000, Nice
Centre Hospitalier De Pau
Neurologie, 4 Boulevard Hauterive, Cs 17595, Pau Cedex
Centre Hospitalier Universitaire De Lille
Neurologie, Avenue Du Professeur Emile Laine, 59037, Lille Cedex
University Hospital Of Clermont-Ferrand
Neurologie, 58 Rue Montalembert, 63003, Clermont Ferrand Cedex 1
Assistance Publique Hopitaux De Paris
Neurologie, 51 Av Du Mal De Lattre De Tassigny, 94000, Creteil
Centre Hospitalier Regional Universitaire De Tours
Neurologie, 2 Boulevard Tonnelle, 37000, Tours
Centre Hospitalier Regional De Marseille
Neurologie, 264 Rue Saint Pierre, 13005, Marseille
Centre Hospitalier Universitaire De Nimes
Neurologie, Place Du Professeur Robert Debre, 30900, Nimes
Besancon University Hospital Center
Neurologie, 3 Boulevard Alexander Fleming, Cs 81816, Besancon Cedex
Centre Hospitalier De Libourne Robert Boulin
Neurologie, 112 Rue De La Marne, Bp 199, Libourne Cedex
Centre Hospitalier Universitaire De Toulouse
Neurologie, 1 Place Du Docteur Joseph Baylac, 31300, Toulouse
Les Hopitaux Universitaires De Strasbourg
Neurologie, 1 Avenue Moliere, Bp 49, Strasbourg Cedex 2
Centre Hospitalier Universitaire De Caen Normandie
Neurologie, Avenue De La Cote De Nacre, Cs 30001, Caen Cedex 9
Hopital Europeen Marseille
Neurologie, 6 Rue Desiree Clary, 13003, Marseille
Centre Hospitalier Universitaire De Dijon
Neurologie, 14 Rue Paul Gaffarel, 21000, Dijon
CHRU De Nancy
Neurologie, 29 Avenue Du Mal De Lattre De Tassigny, 54000, Nancy
Centre Hospitalier Notre Dame De La Misericorde
Neurologie, Route A Madunuccia, 20090, Ajaccio
Centre Hospitalier De La Cote Basque
Neurologie, 13 Avenue Interne Jacques Loeb, 64100, Bayonne
Groupement Des Hopitaux De L'Institut Catholique De Lille
Neurologie, Boulevard De Belfort, P. O. Box 387, Lille Cedex
Centre Hospitalier Universitaire De Rennes
Neurologie, 2 Rue Henri Le Guilloux, 35000, Rennes
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 17 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | 2024-513292-40-00_Protocol_FP | 1.4 |
| Recruitment arrangements (for publication) | 2024-513292-40-00_Recruitment arrangements | 1 |
| Subject information and informed consent form (for publication) | 2024-513292-40-00_Informed Consent Form | 1.1 |
| Subject information and informed consent form (for publication) | 2024-513292-40-00_Patient Diary | 1 |
| Subject information and informed consent form (for publication) | 2024-513292-40-00_Subject Information Sheet | 1.1 |
| Summary of Product Characteristics (SmPC) (for publication) | 2024-513292-40-00_SmPC_Aubagio_Teriflunomide | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | 2024-513292-40-00_SmPC_Avonex_Interferon beta 1a | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | 2024-513292-40-00_SmPC_Copaxone 20_Glatiramere | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | 2024-513292-40-00_SmPC_Copaxone 40_Glatiramere | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | 2024-513292-40-00_SmPC_Kesimpta_Ofatumumab | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | 2024-513292-40-00_SmPC_Mabthera_Rituximab | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | 2024-513292-40-00_SmPC_Ocrevus_Ocrelizumab | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | 2024-513292-40-00_SmPC_Plegridy_Peginterferon beta 1a | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | 2024-513292-40-00_SmPC_Rebif_Interferon beta 1a | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | 2024-513292-40-00_SmPC_Tecfidera_Dimethyl fumarate | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | 2024-513292-40-00_SmPC_Vumerity_Diroximel fumarate | 2 |
| Synopsis of the protocol (for publication) | 2024-513292-40-00_Synopsis | 1.2 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-12-13 | France | Acceptable 2025-04-22
|
2025-04-28 |