Understanding the 'Durable Effect' Concept of B-cell Modulating Therapies

NCT ID: NCT06586177

Last Updated: 2025-09-18

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-10-27
• Study Completion Date: 2028-12-31

Brief Summary

This prospective, observational clinical study aims to longitudinally assess peripheral immune cell profiles of patients with relapsing-remitting multiple sclerosis (RRMS) receiving anti-CD20 therapy with ofatumumab (OFA), ocrelizumab (OCR), ublituximab (UBX), and rituximab (RTX). Throughout the study, clinical data - including relapse events, patient scores, and neuropsychological parameters - will be collected, along with results from imaging techniques such as Optical Coherence Tomography (OCT) and Magnetic Resonance Imaging (MRI). This clinical data will be combined with immunological analyses, including multidimensional flow cytometry (mFC), bulk RNA sequencing (bulk-Seq), T and B cell receptor sequencing (TCR/BCR-Seq), proteomics, and immunoglobulin analysis. This approach aims to enable a detailed characterization of changes in the immune cell repertoire and their impact on the clinical disease course.

Detailed Description

B cell targeted therapies have become a key element in the treatment of multiple sclerosis due to their effectiveness in rapid and long-lasting depletion of B cells in peripheral blood (PB), significantly reducing relapse rates and disability progression. The monoclonal antibodies OFA, OCR, UBX, and RTX target the B cell surface protein CD20, however it is unclear how B cell depletion and subsequent repopulation allows for immune system reconstitution and how other immune cell populations are affected by these therapies. Furthermore, the relevance of immune cell changes - beyond B cell depletion - for clinical disease stability remains insufficiently understood.

By collecting comprehensive and structured prospective clinical data alongside immunological analyses, this study aims for a better understanding of immunological changes in RRMS patients receiving anti-CD20 therapies and the implications of those alterations in immune cell profiles on the clinical disease course. REBELLION-MS plans for two patient cohorts: cohort 1 (C1; basic cohort) and cohort 2 (C2; in-depth cohort). Participants in C1 will be seen every 6 months up until month 24, then every 12 months. The following parameters will be collected: demographic data, disease characteristics incl. Expanded Disability Status Scale (EDSS) and magnetic resonance imaging (MRI) data, serum samples, and Peripheral Blood Mononuclear Cells (PBMCs). Furthermore, Short Form-36 (SF-36) and Fatigue Scale for Motor and Cognitive Functions (FSMC) are documented. Participants of C2 will receive additional evaluations: clinical evaluation incl. EDSS and sampling of serum and PBMCs at months 1 and 3, Multiple sclerosis functional composite (MFSC) every 6 months, and optical coherence tomography (OCT) as well as neuropsychological assessment (NPT) every 12 months. Serum samples and PBMCs will be analyzed by mFC, bulk-Seq, TCR/BCR-Seq, and proteomics, among other methods.

Conditions

Relapsing-remitting Multiple Sclerosis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Cohort 1 (C1; basic cohort)

Participants will be seen every 6 months up until month 24, then every 12 months. The following parameters will be collected: demographic data, disease characteristics incl. EDSS and MRI data, serum samples, and PBMCs. Furthermore, SF-36 and FSMC are documented.

Anti-CD20 antibody

Intervention Type: DRUG

Study participants receive an anti-CD20 antibody according to the summary of product characteristics.

Cohort 2 (C2; in-depth cohort)

In addition to the parameters collected for C1, participants of C2 will receive: clinical evaluation incl. EDSS and sampling of serum and PBMCs at months 1 and 3, MFSC every 6 months, and OCT as well as NPT every 12 months.

Anti-CD20 antibody

Intervention Type: DRUG

Study participants receive an anti-CD20 antibody according to the summary of product characteristics.

Interventions

Anti-CD20 antibody

Study participants receive an anti-CD20 antibody according to the summary of product characteristics.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Diagnosed relapsing-remitting multiple sclerosis (RRMS) according to 2017 revised McDonald criteria
• Current treatment with B cell modulating therapies or initiation/transition to B cell modulating therapies according to the "Summary of Product Characteristics (SmPC)"
• EDSS score of 0.0 to 7.0

Exclusion Criteria

• Previous treatment with alemtuzumab, cladribine, cyclophosphamide, mitoxantrone, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, total body irradiation or bone marrow transplantation
• Medical, psychiatric, cognitive, or other conditions that, in the opinion of the investigator, impair the patient's ability to understand the patient information and give informed consent
• Patients receiving immunosuppressive treatment for conditions other than MS or long-term corticosteroid treatment
• Patients with confirmed infection by the Human Immunodeficiency Virus or Hepatitis C Virus

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

Heinrich-Heine University, Duesseldorf

OTHER

Sponsor Role: lead

Responsible Party

Univ.-Prof. Dr. med. Dr rer. nat. Sven Meuth

Chairman

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Heinrich-Heine University, Duesseldorf

Düsseldorf, , Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Saskia Räuber, MD

Role: CONTACT

SaskiaJanina.Raeuber@med.uni-duesseldorf.de

+492118117889

Alice Willison, MD

Role: CONTACT

AliceGrizzel.Willison@med.uni-duesseldorf.de

+492118117889

Facility Contacts

Saskia Räuber, MD

Role: primary

SaskiaJanina.Raeuber@med.uni-duesseldorf.de

+492118117889

Alice Willison, MD

Role: backup

AliceGrizzel.Willison@med.uni-duesseldorf.de

+492118117889

References

Willison AG, Hagler R, Weise M, Elben S, Huntemann N, Masanneck L, Pfeuffer S, Lichtenberg S, Golombeck KS, Preuth LM, Rolfes L, Ozturk M, Ruck T, Melzer N, Korsen M, Hauser SL, Hartung HP, Lang PA, Pawlitzki M, Rauber S, Meuth SG. Effects of Anti-CD20 Antibody Therapy on Immune Cell Dynamics in Relapsing-Remitting Multiple Sclerosis. Cells. 2025 Apr 6;14(7):552. doi: 10.3390/cells14070552.

Reference Type: DERIVED

PMID: 40214505 (View on PubMed)

Other Identifiers

2021-1475

Identifier Type: -

Identifier Source: org_study_id