RItuximab Versus Ocrelizumab in Relapsing-remitting Multiple Sclerosis.

NCT ID: NCT05758831

Last Updated: 2024-04-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

386 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-06-01

Study Completion Date

2030-05-01

Brief Summary

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The goal of this randomized clinical trial is to compare relapse remitting multiple sclerosis (RRMS) patients treated by ocrelizumab or by rituximab followed for 2 years. The main question it aims to answer is : • to demonstrate the non-inferiority of rituximab versus ocrelizumab in active relapsing MS patients on the % of patients without disease activity at 2 years.

During the 2 years, the study includes 6 follow-up visits and the completion of various health and quality of life questionnaires. The protocol visits follow the usual schedule of treatment infusions for the disease (at initiation of treatment, 15 days after, and then every 6 months).

Two comparison groups: Researchers will compare rituximab treated patients versus ocrelizumab treated patients to see the % of patients without disease activity at 2 years.

Detailed Description

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Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS). This disease is the leading cause of non-traumatic disability in young adults and France is characterized by a high prevalence (currently 1/1000 inhabitants) of MS.

Clinical trials with B cell depleting therapies have shown efficacy in relapsing-remitting MS (RRMS) and are increasingly perceived as an important addition to the existing panel of Disease-modifying treatments (DMTs). Rituximab, a mouse chimeric anti CD20, is approved for non-Hodgkin's lymphoma, chronic lymphocytic leukemia, certain forms of vasculitis and Rheumatoid Arthritis with first marketing approval in 1998. Rituximab has undergone clinical testing in RRMS in 2008 in a phase II placebo-controlled trial, demonstrating the clinico-radiological efficacy in 104 patients. Despite these promising results and the absence of adverse events, its clinical development was interrupted by the manufacturer (Roche). However, for several years, rituximab has been increasingly prescribed (off-label) in Europe and USA in patients refractory to first-line therapies, with a very good safety and efficacy. Thus, rituximab is prescribed for 40% of RRMS patients treated in Sweden. Roche has then developed a humanized anti-CD20 monoclonal antibody (Ocrelizumab). Two phase III clinical trials (OPERA I and II) have demonstrated its efficacy in active RRMS. Ocrelizumab has just been authorized in France in this indication: RRMS patients with active disease (clinical or radiological). So, it can be prescribed as a first line or second line therapy in active RRMS patients.

According to literature, there are no biological arguments to think that ocrelizumab could be more effective in active RRMS compared to rituximab. Moreover, regarding safety, rituximab has been used for other indications for almost two decades and no serious concern has arisen.

The high cost of this new antibody (x6 to 10) compared to rituximab) makes it wonder about its place inside the anti-CD20 therapeutic strategy compared to rituximab for treating relapsing MS patients.

Hypothesis: Researchers hypothesize that rituximab and ocrelizumab have the same efficacy in active RRMS patients. Indeed, if the non-inferiority of rituximab on the % of patients without disease activity is confirmed by the trial, the potential medico-economic benefit from a societal perspective will be a strong argument to ask for authorization of rituximab in active RRMS.

Conditions

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Multiple Sclerosis Relapsing-remitting Multiple Sclerosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

multicenter, prospective, comparative (non inferiority), randomized, double blinded phase III/IV study
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Randomisation code transmitted to the pharmacy preparing the treatment. Blind labelling of treatments

Study Groups

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Ocrelizumab

Day 0 (300mg), Day 15(300mg), and then 300 mg every 6 months (M6, M12, M18 and M24)

Group Type ACTIVE_COMPARATOR

Perfusion of treatment Ocrelizumab

Intervention Type DRUG

Perfusion of treatment (Ocrevus®)

Rituximab

Day 0 (1000mg), Day 15 (1000 mg), and then 500 mg every 6 months (M6, M12, M18 and M24)

Group Type EXPERIMENTAL

Perfusion of treatment Rituximab

Intervention Type DRUG

Perfusion of treatment (Mabthera®, Truxima®, Rixathon®, Ruxience®)

Interventions

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Perfusion of treatment Rituximab

Perfusion of treatment (Mabthera®, Truxima®, Rixathon®, Ruxience®)

Intervention Type DRUG

Perfusion of treatment Ocrelizumab

Perfusion of treatment (Ocrevus®)

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Patients presenting a relapsing remitting MS according to Mac Donald 2017 criteria, with clinical or radiological criteria of activity (ie at least one relapse AND/OR one new T2 lesion in the last 12 months before inclusion);
* Age between 18 and 55 years
* EDSS ≤ 5
* Brain MRI within 6 months before inclusion
* For women of childbearing potential\*: effective contraception (effective contraception include oral contraception, intrauterine devices and other forms of contraception with failure rate \<1%, for the duration of the study and until 12 months after last dose administered) \* A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.

A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.

* Having signed an informed consent form
* Patients covered with social insurance


* Secondary or primary progressive MS;
* Previous treatment by mitoxantrone, cladribine, alemtuzumab and anti CD20 therapies in the last two years;
* Previous treatment by fingolimod or natalizumab in the last 4 weeks;
* Treatment with high dose corticosteroids during the 30 days preceding the inclusion;
* Occurrence of a relapse less than 30 days before inclusion;
* Pregnancy or breastfeeding;
* Other neurologic or systemic disease;
* Concomitant participation or Participation in another therapeutic trial in the last 6 months;
* Incapacity to understand or sign the consent form;
* Contraindication to MRI;
* Contraindication to anti-CD20 therapies:

* Receipt of a live or live-attenuated vaccine within 6 weeks prior to randomization
* Active malignancy.
* Any ongoing infection
* Severe heart failure (New York Heart Association Class IV) or severe uncontrolled cardiac disease
* Positive test for HIV, hepatitis B or C, or tuberculosis
* Severe immune deficiency:
* Lymphopenia grade 3 (0.2 to 0.5 × 10\^9/L) or higher grades
* Neutropenia grade 3 (0.5 to 1.0 × 10\^9/L) or higher grades

* Known hypersensitivity or other known side effects for any of the study medications, including co-medications such as high glucocorticosteroids
* AST or ALT \>=3ULN
* Platelet (thrombocyte) count \< 100 x 10\^9/L
* Adults legally protected (under judicial protection, guardianship, or supervision), persons deprived of their liberty.
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Rennes University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Hospices Civils de Lyon Hôpital Neurologique Pierre Wertheimer

Lyon, Bron, France

Site Status NOT_YET_RECRUITING

CHRU de Brest - Hôpital la Cavale Blanche

Brest, , France

Site Status NOT_YET_RECRUITING

Centre Hospitalier Universitaire de Caen

Caen, , France

Site Status RECRUITING

Centre Hospitalier de Pontoise - GHT NOVO

Cergy-Pontoise, , France

Site Status NOT_YET_RECRUITING

Hôpital Gabriel Montpieds

Clermont-Ferrand, , France

Site Status NOT_YET_RECRUITING

Centre hospitalier de Gonnesse

Gonesse, , France

Site Status NOT_YET_RECRUITING

Groupe Hospitalier de l'Institut Catholique de Lille

Lille, , France

Site Status NOT_YET_RECRUITING

Centre Hospitalier Universitaire de Limoges

Limoges, , France

Site Status NOT_YET_RECRUITING

AP-HM - Hôpital la Timone

Marseille, , France

Site Status RECRUITING

CHRU de Montpellier - Hôpital Gui de Chauliac

Montpellier, , France

Site Status RECRUITING

Centre Hospitalier Régional de Nancy

Nancy, , France

Site Status RECRUITING

CHU de Nantes -Hôpital Nord Laennec

Nantes, , France

Site Status RECRUITING

CHU de Nice - Hôpital Pasteur 2

Nice, , France

Site Status RECRUITING

CHU de Nîmes - Hôpital Caremeau

Nîmes, , France

Site Status NOT_YET_RECRUITING

AP-HP Höpital la Pitié-Salpétrière

Paris, , France

Site Status NOT_YET_RECRUITING

Groupe Hospitalier Universitaire Henri Mondor

Paris, , France

Site Status NOT_YET_RECRUITING

Hôpital Saint-Germain

Poissy, , France

Site Status NOT_YET_RECRUITING

Centre Hospitalier de Cornouaille

Quimper, , France

Site Status RECRUITING

Centre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou

Rennes, , France

Site Status RECRUITING

CHU de Rouen - Hôpital Charles Nicolle

Rouen, , France

Site Status NOT_YET_RECRUITING

CHRU de Strasbourg - Hôpital Hautpierre

Strasbourg, , France

Site Status RECRUITING

Hôpital Foch

Suresnes, , France

Site Status NOT_YET_RECRUITING

CHU de Toulouse - Bâtiment Pierre Paul Riquet

Toulouse, , France

Site Status NOT_YET_RECRUITING

Countries

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France

Central Contacts

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Laure MICHEL, MD

Role: CONTACT

0299286774

Agnès Gazzola

Role: CONTACT

0299289194

Facility Contacts

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Sandra VUKUSIC, MD

Role: primary

Aurore JOURDAIN, MD

Role: primary

Gilles DEFER, MD

Role: primary

Philippe NICLOT, MD

Role: primary

Pierre CLAVELOU, MD

Role: primary

Eric MANCHON, MD

Role: primary

Julien POUPARD, MD

Role: primary

Laurent MAGY, MD

Role: primary

Bertrand AUDOIN, MD

Role: primary

Pierre LABAUGE, MD

Role: primary

Guillaume MATHEY, MD

Role: primary

David LAPLAUD, MD

Role: primary

Christine LEBRUN-FRENAY, MD

Role: primary

Eric THOUVENOT, MD

Role: primary

Céline LOUAPRE, MD

Role: primary

Alain CREANGE, MD

Role: primary

Olivier HEINZLEF, MD

Role: primary

Marc COUSTANS, MD

Role: primary

Laure MICHEL, MD

Role: primary

Bertrand BOURRE, MD

Role: primary

Jérôme DE SEZE, MD

Role: primary

TCHIKVILADZE Maia, MD

Role: primary

Jonathan CIRON, MD

Role: primary

Other Identifiers

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35RC20_9812_TRIO

Identifier Type: -

Identifier Source: org_study_id

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