Clinical trial NCT06586177: Understanding the 'durable Effect' Concept of B-cell Modulating Therapies
Official title: Understanding the 'durable Effect' Concept of B-cell Modulating Therapies
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Relapsing-remitting Multiple Sclerosis
Lead sponsor: Heinrich-Heine University, Duesseldorf
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2024-09-19
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will include RRMS patients receiving B cell modulating therapies.

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.

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

Primary outcomes:
measure: Change from baseline in the peripheral immune cell profile
timeFrame: Baseline up to 48 months
measure: Change from baseline in protein profile of the peripheral blood
timeFrame: Baseline up to 48 months
measure: Change from baseline in TCR/BCR profile
timeFrame: Baseline up to 48 months
Secondary outcomes:
measure: Change from baseline in Expanded Disability Status Scale (EDSS) Score
timeFrame: Baseline up to 48 months
measure: Change from baseline in Short Form Health Survey (SF-36)
timeFrame: Baseline up to 48 months
measure: Change from baseline on Magnetic Resonance Imaging (MRI)
timeFrame: Baseline up to 48 months
measure: Change from baseline in Retinal Nerve Fiber Layer thickness (RNFL)
timeFrame: Baseline up to 48 months
measure: Change from baseline in visual acuity (HCV and LCV)
timeFrame: Baseline up to 48 months
measure: Change from baseline in Fatigue Scale for Motor and Cognitive Functions (FSMC)
timeFrame: Baseline up to 48 months
measure: Change from baseline in Multiple Sclerosis Functional Composite (MSFC) Score
timeFrame: Baseline up to 48 months
measure: Change from baseline in Symbol Digit Modalities Test (SDMT)
timeFrame: Baseline up to 48 months
measure: Change from baseline in Verbal Memory Learning Test (VMLT)
timeFrame: Baseline up to 48 months
measure: Change from baseline in Brief Visuospatial Memory Test (BVMT)
timeFrame: Baseline up to 48 months
measure: Change from baseline in Montreal Cognitive Assessment (MoCA)
timeFrame: Baseline up to 48 months
measure: Change from baseline in BDI-FS/BDI II
timeFrame: Baseline up to 48 months
Other outcomes:
Locations:
city: Düsseldorf
country: Germany
facility: Heinrich-Heine University, Duesseldorf
Study officials:
References: