Clinical trial • Phase III • Neurology

OFATUMUMAB for Multiple sclerosis | Relapsing-remitting multiple sclerosis

Phase III trial of OFATUMUMAB for Multiple sclerosis | Relapsing-remitting multiple sclerosis.

Overview

Trial Therapeutic Area
Neurology
Trial Disease
Multiple sclerosis | Relapsing-remitting multiple sclerosis
Trial Stage
Phase III
Drug Modality
Monoclonal antibody | Small molecule | Peptide/protein/enzyme

Key dates

Initial CTIS Submission Date
13-12-2024
First CTIS Authorization Date
28-04-2025

Trial design

Randomised, control group: anti-cd20 maintenance (ocrelizumab, rituximab given every 6 months or up to one year at the same interval dosing for extended-interval iv dosing; ofatumumab subcutaneous every 4 weeks) from randomization to m36. experimental group: platform therapies (dimethyl fumarate, diroximel fumarate, teriflunomide, glatiramer acetate, beta-interferons) from randomization to m36. Phase III trial across 27 sites in France.

Randomised
Yes
Comparator
Control group: anti-CD20 maintenance (ocrelizumab, rituximab given every 6 months or up to one year at the same interval dosing for extended-interval IV dosing; ofatumumab subcutaneous every 4 weeks) from randomization to M36. Experimental group: platform therapies (Dimethyl Fumarate, Diroximel fumarate, Teriflunomide, Glatiramer Acetate, Beta-interferons) from randomization to M36.
Target Sample Size
250
Trial Duration For Participant
1095

Eligibility

Recruits 250 Protected populations are explicitly excluded: "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)". In addition, "Failure to obtain written informed consent after a reflection period" is an exclusion, indicating written informed consent is required; no assent procedures for minors are described (trial population is adults ≥40)..

Pregnancy Exclusion
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)
Vulnerable Population
Protected populations are explicitly excluded: "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)". In addition, "Failure to obtain written informed consent after a reflection period" is an exclusion, indicating written informed consent is required; no assent procedures for minors are described (trial population is adults ≥40).

Inclusion criteria

  • {"criterion_text":"- Patients ≥40 years at inclusion\n- 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\n- No evidence of disease activity for the last 3 years on anti-CD20 (No relapse AND no new/enlarged MRI lesion)\n- Brain MRI performed according to OFSEP protocol within a maximum of 6 months before randomization"}

Exclusion criteria

  • {"criterion_text":"- Secondary or primary progressive MS at inclusion\n- Significantly impaired bone marrow function or significant anaemia, leukopenia, neutropenia or thrombocytopenia\n- Severe renal impairment undergoing dialysis\n- Severe hypoproteinaemia\n- Current severe depression and/or suicidal ideation\n- Suspected or confirmed progressive multifocal leukoencephalopathy (PML)\n- 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\n- Participation in another therapeutic trial in the last 6 months\n- 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)\n- All women of childbearing age not using effective contraception during the study\n- Subjects not covered by public health insurance\n- Previous experience of treatment failure in patients treated with natalizumab, fingolimod, rituximab, ocrelizumab, mitoxantrone, alemtuzumab or cladribine\n- Failure to obtain written informed consent after a reflection period\n- Treatment with high dose corticosteroids during the 30 days preceding inclusion\n- Contraindication to MRI\n- Severely immunocompromised state\n- Current severe active infection\n- Known active malignancy\n- Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease\n- Severe hepatic impairment (Child-Pugh class C)"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"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

  • {"endpoint_text":"- Relapses","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Disability","definition_or_measurement_approach":""}
  • {"endpoint_text":"- New/enlarged T2/FLAIR lesions","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Adverse event and severe adverse events","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Infections and serious infections","definition_or_measurement_approach":""}
  • {"endpoint_text":"- B-cells counts","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Serum immunoglobulin levels (IgG, A, M)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Brain volume","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Neurofilaments light chain values","definition_or_measurement_approach":""}
  • {"endpoint_text":"- EQ5D-5L score","definition_or_measurement_approach":""}
  • {"endpoint_text":"- MUSICARE score","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Incremental cost-utility ratio at year 3","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Annual budget impact from the SNDS (Système National des Données de Santé hosted by French Health Insurance)","definition_or_measurement_approach":""}

Recruitment

Planned Sample Size
250
Recruitment Window Months
60
Consent Approach
Written informed consent is required; failure to obtain written informed consent after a reflection period is an exclusion. Subject information and informed consent documents are provided (Subject Information Sheet; Informed Consent Form). Participants are adults (≥40); no assent for minors is described. Languages of documents not specified in the available records.

Geography

Total Number Of Sites
27
Total Number Of Participants
250

France

Earliest CTIS Part Ii Submission Date
10-03-2025
Latest Decision Or Authorization Date
28-04-2025
Processing Time Days
49
Number Of Sites
27
Number Of Participants
250

Sites

Site Name
Centre Hospitalier De Libourne Robert Boulin
Department Name
Neurologie
Contact Person Name
Philippe CASENAVE
Site Name
Besancon University Hospital Center
Department Name
Neurologie
Contact Person Name
Eric BERGER
Contact Person Email
eberger@chu-besancon.fr
Site Name
Centre Hospitalier Regional De Marseille
Department Name
Neurologie
Contact Person Name
Bertrand AUDOIN
Contact Person Email
Bertrand.audoin@ap-hm.fr
Site Name
Hospital Foch
Department Name
Neurologie
Contact Person Name
Maia TCHIKVILADZE
Contact Person Email
m.tchikviladze@hopital-foch.fr
Site Name
Centre Hospitalier Universitaire Rouen
Department Name
Neurologie
Contact Person Name
Bertrand BOURRE
Contact Person Email
bertrand.bourre@chu-rouen.fr
Site Name
Centre Hospitalier Universitaire De Montpellier
Department Name
Neurologie
Contact Person Name
Xavier AYRIGNAC
Contact Person Email
x-ayrignac@chu-montpellier.fr
Site Name
Les Hopitaux Universitaires De Strasbourg
Department Name
Neurologie
Contact Person Name
Jérôme DE SEZE
Site Name
Centre Hospitalier Universitaire De Dijon
Department Name
Neurologie
Contact Person Name
Thibault MOREAU
Contact Person Email
thibault.moreau@chu-dijon.fr
Site Name
Centre Hospitalier Notre Dame De La Misericorde
Department Name
Neurologie
Contact Person Name
Pierre DUROZARD
Contact Person Email
pierre.durozard@ch-ajaccio.fr
Site Name
Centre Hospitalier Universitaire De Nice
Department Name
Neurologie
Contact Person Name
Mikael COHEN
Contact Person Email
cohen.m@chu-nice.fr
Site Name
CHRU De Nancy
Department Name
Neurologie
Contact Person Name
Guillaume MATHEY
Contact Person Email
g.mathey@chru-nancy.fr
Site Name
Centre Hospitalier Intercommunal De Poissy Saint Germain
Department Name
Neurologie
Contact Person Name
Olivier HEINZLEF
Site Name
Centre Hospitalier De La Cote Basque
Department Name
Neurologie
Contact Person Name
Patricia BERNADY
Contact Person Email
pbernady@ch-cotebasque.fr
Site Name
Centre Hospitalier Universitaire De Bordeaux
Department Name
Neurologie
Contact Person Name
Amélie RUET
Contact Person Email
aurelie.ruet@chu-bordeaux.f
Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Neurologie
Contact Person Name
Hélène ZÉPHIR
Contact Person Email
helene.zephir@chru-lille.fr
Site Name
Centre Hospitalier Universitaire De Rennes
Department Name
Neurologie
Contact Person Name
Laure MICHEL
Contact Person Email
laure.michel@chu-rennes.fr
Site Name
University Hospital Of Clermont-Ferrand
Department Name
Neurologie
Contact Person Name
Pierre CLAVELOU
Site Name
Centre Hospitalier Universitaire De Nantes
Department Name
Neurologie
Contact Person Name
Sandrine WIERTLEWSKI
Site Name
Centre Hospitalier Universitaire De Caen Normandie
Department Name
Neurologie
Contact Person Name
Pierre BRANGER
Contact Person Email
branger-p@chu-caen.fr
Site Name
Centre Hospitalier De Pau
Department Name
Neurologie
Contact Person Name
Camille DAHAN
Contact Person Email
camille.dahan@chu-pau.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Neurologie
Contact Person Name
Alain CREANGE
Contact Person Email
alain.creange@aphp.fr
Site Name
Hopital Europeen Marseille
Department Name
Neurologie
Contact Person Name
Laurent SUCHET
Contact Person Email
l.suchet@hopital-europeen.fr
Site Name
Centre Hospitalier Universitaire Grenoble Alpes
Department Name
Neurologie
Contact Person Name
Mathieu VAILLANT
Contact Person Email
MVaillant@chu-grenoble.fr
Site Name
Centre Hospitalier Universitaire De Nimes
Department Name
Neurologie
Contact Person Name
Eric THOUVENOT
Contact Person Email
Eric.thouvenot@chu-nimes.fr
Site Name
Centre Hospitalier Universitaire De Toulouse
Department Name
Neurologie
Contact Person Name
Jonathan CIRON
Contact Person Email
ciron.j@chu-toulouse.fr
Site Name
Centre Hospitalier Regional Universitaire De Tours
Department Name
Neurologie
Contact Person Name
Inès DOGHRI
Contact Person Email
i.doghri@chu-tours.fr
Site Name
Groupement Des Hopitaux De L'Institut Catholique De Lille
Department Name
Neurologie
Contact Person Name
Arnaud KWIATKOWSKI
Contact Person Email
kwiatkowski.arnaud@ghicl.net

Sponsor

Primary sponsor

Full Name
Centre Hospitalier Universitaire De Montpellier
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
France

Investigational products

Investigational Product Name
OFATUMUMAB
Active Substance
OFATUMUMAB
Modality
Monoclonal antibody
Routes Of Administration
Subcutaneous injection
Route
Subcutaneous injection
Authorisation Status
Authorised
Maximum Dose
20 mg
Investigational Product Name
DIMETHYL FUMARATE
Active Substance
DIMETHYL FUMARATE
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Authorisation Status
Authorised
Maximum Dose
240 mg
Investigational Product Name
OCRELIZUMAB
Active Substance
OCRELIZUMAB
Modality
Monoclonal antibody
Routes Of Administration
Intravenous infusion
Route
Intravenous infusion
Authorisation Status
Authorised
Maximum Dose
600 mg
Investigational Product Name
PEGINTERFERON BETA-1A
Active Substance
PEGINTERFERON BETA-1A
Modality
Peptide/protein/enzyme
Routes Of Administration
Subcutaneous injection
Route
Subcutaneous injection
Authorisation Status
Authorised
Maximum Dose
125 µg
Investigational Product Name
TERIFLUNOMIDE
Active Substance
TERIFLUNOMIDE
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Authorisation Status
Authorised
Maximum Dose
14 mg
Investigational Product Name
GLATIRAMER ACETATE
Active Substance
GLATIRAMER ACETATE
Modality
Peptide/protein/enzyme
Routes Of Administration
Subcutaneous injection
Route
Subcutaneous injection
Authorisation Status
Authorised
Maximum Dose
120 mg
Investigational Product Name
DIROXIMEL FUMARATE
Active Substance
DIROXIMEL FUMARATE
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Authorisation Status
Authorised
Maximum Dose
924 mg
Investigational Product Name
INTERFERON BETA-1A
Active Substance
INTERFERON BETA-1A
Modality
Peptide/protein/enzyme
Routes Of Administration
Subcutaneous injection | Intramuscular injection
Route
Subcutaneous injection / Intramuscular injection
Authorisation Status
Authorised
Maximum Dose
132 µg
Investigational Product Name
RITUXIMAB
Active Substance
RITUXIMAB
Modality
Monoclonal antibody
Routes Of Administration
Intravenous infusion
Route
Intravenous infusion
Authorisation Status
Authorised
Maximum Dose
1000 mg

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