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

NCT06586177 | Recruiting

• 1 other identifier: 2021-1475
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Relapsing-remitting Multiple Sclerosis

Outcome Measures

Primary Outcomes (3)

• Change from baseline in the peripheral immune cell profile

  Immune cell subpopulations will be analyzed longitudinally by multidimensional flow cytometry \[% of all living cells and mean fluorescent intensity of different cell surface markers\].

  Baseline up to 48 months

• Change from baseline in protein profile of the peripheral blood

  Protein expression will be measured longitudinally using proteomics.

  Baseline up to 48 months

• Change from baseline in TCR/BCR profile

  T cell and B cell receptor profile will be measured longitudinally using BCR- and TCR-sequencing.

  Baseline up to 48 months

Secondary Outcomes (12)

• Change from baseline in Expanded Disability Status Scale (EDSS) Score

  Baseline up to 48 months

• Change from baseline in Short Form Health Survey (SF-36)

  Baseline up to 48 months

• Change from baseline on Magnetic Resonance Imaging (MRI)

  Baseline up to 48 months

• Change from baseline in Retinal Nerve Fiber Layer thickness (RNFL)

  Baseline up to 48 months

• Change from baseline in visual acuity (HCV and LCV)

  Baseline up to 48 months

Study Arms (2)

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.

Drug: Anti-CD20 antibody

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.

Drug: Anti-CD20 antibody

Interventions

Anti-CD20 antibody DRUG

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

Cohort 1 (C1; basic cohort); Cohort 2 (C2; in-depth cohort)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The study population will include RRMS patients receiving B cell modulating therapies.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Heinrich-Heine University, Duesseldorf: lead
• Novartis: collaborator

Study Sites (1)

Heinrich-Heine University, Duesseldorf

Düsseldorf, 40225, Germany

RECRUITING

Related Publications (1)

• 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.

  PMID: 40214505 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Central Study Contacts

Saskia Räuber, MD

CONTACT

+492118117889; SaskiaJanina.Raeuber@med.uni-duesseldorf.de

Alice Willison, MD

CONTACT

+492118117889; AliceGrizzel.Willison@med.uni-duesseldorf.de

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chairman

Study Record Dates

• First Submitted: July 4, 2024
• First Posted: September 19, 2024
• Study Start: October 27, 2021
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: September 18, 2025

Record last verified: 2025-09

Locations

DE (1)