Understanding the 'Durable Effect' Concept of B-cell Modulating Therapies
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18-60
SponsorHeinrich-Heine University, Duesseldorf
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial population
The study population will include RRMS patients receiving B cell modulating therapies.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Anti-CD20 antibody
DrugStudy participants receive an anti-CD20 antibody according to the summary of product characteristics.
Treatment groups
100 Participants
are divided into 2 treatment groupsGroup A: Cohort 1 (C1; basic cohort)1 intervention
Group B: Cohort 2 (C2; in-depth cohort)1 intervention
Trial outcomes
Primary outcomes
1
Change from baseline in the peripheral immune cell profile
Immune cell subpopulations will be analyzed longitudinally by multidimensional flow cytometry \[% of all living cells and mean fluorescent intensity of different cell surface markers\].
Time frame
Baseline up to 48 months2
Change from baseline in protein profile of the peripheral blood
Protein expression will be measured longitudinally using proteomics.
Time frame
Baseline up to 48 months3
Change from baseline in TCR/BCR profile
T cell and B cell receptor profile will be measured longitudinally using BCR- and TCR-sequencing.
Time frame
Baseline up to 48 monthsSecondary outcomes
1
Change from baseline in Expanded Disability Status Scale (EDSS) Score
The EDSS is used to quantify disability due to symptoms of MS and to track changes in disability status over time. Scores range from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). Higher scores indicate a greater level of disability.
Time frame
Baseline up to 48 months2
Change from baseline in Short Form Health Survey (SF-36)
The SF-36 questionnaire is used to measure health-related quality of life summarized into two overarching scales: physical health and mental health. It contains 36 questions including eight subscales that capture various aspects of health and well-being. For each of these subscales, multiple questions are asked, each rated on a scale from 0 to 100, with higher scores indicating better health and higher levels of well-being.
Time frame
Baseline up to 48 months3
Change from baseline on Magnetic Resonance Imaging (MRI)
Cerebral MRI (cMRI) and spinal MRI (sMRI) performed as part of the clinical routine workup will be analyzed and quantified for the number of lesions, new lesions, and active lesions.
Time frame
Baseline up to 48 months4
Change from baseline in Retinal Nerve Fiber Layer thickness (RNFL)
Retinal Nerve Fiber Layer thickness (RNFL) will be measured longitudinally by Optical Coherence Tomography (OCT).
Time frame
Baseline up to 48 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Heinrich-Heine University, Duesseldorf
Lead sponsor
Novartis
Collaborator
Source ClinicalTrials.gov