Relapsing-remitting Multiple SclerosisREBELLION-MSNCT06586177
Understanding the 'Durable Effect' Concept of B-cell Modulating Therapies
An observational study of Relapsing-remitting Multiple Sclerosis, run by Heinrich-Heine University, Duesseldorf at 1 site in Germany.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Relapsing-remitting Multiple Sclerosis
- What is being tested?
- Anti-CD20 antibody
- How many people
- 100 participants
- Where
- 1 siteGermany
- Study dates
- 27 Oct 2021to 31 Dec 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Adult
Study population: The study population will include RRMS patients receiving B cell modulating therapies.
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Germany1 site, 1 recruiting
- Recruiting
Heinrich-Heine University, Duesseldorf
Düsseldorf, 40225
Saskia Räuber, MD, +492118117889, SaskiaJanina.Raeuber@med.uni-duesseldorf.de
Alice Willison, MD, +492118117889, AliceGrizzel.Willison@med.uni-duesseldorf.de
About this study
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.
Read the 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
- Being tested
- Anti-CD20 antibody
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-CD20 antibodyDrug
Study participants receive an anti-CD20 antibody according to the summary of product characteristics.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Anti-CD20 antibody |
What is being measured
The primary outcome is the main question the study is designed to answer.
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].
Measured: Baseline up to 48 months
Change from baseline in protein profile of the peripheral blood
Protein expression will be measured longitudinally using proteomics.
Measured: 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.
Measured: Baseline up to 48 months
Secondary outcomes (12)
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.
Measured: Baseline up to 48 months
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.
Measured: Baseline up to 48 months
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.
Measured: Baseline up to 48 months
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).
Measured: Baseline up to 48 months
Change from baseline in visual acuity (HCV and LCV)
High-contrast visual acuity (HCV) and low-contrast visual acuity (LCV) are measured longitudinally in both eyes.
Measured: Baseline up to 48 months
Change from baseline in Fatigue Scale for Motor and Cognitive Functions (FSMC)
Fatigue is rated using the self-administered 20-item FSMC questionnaire that includes ten questions related to motor fatigue and ten questions related to cognitive fatigue. A Likert-type 5-point scale produces a score between 1 and 5 for each scored question. Minimum value is 20 (no fatigue at all) and maximum value is 100 (severe fatigue). Higher scores indicate higher fatigue.
Measured: Baseline up to 48 months
Change from baseline in Multiple Sclerosis Functional Composite (MSFC) Score
MSFC has 3 components: 1. Timed 25-foot walk (T25FW), 2. 9-hole peg test (9HPT) [dominant and nondominant hands], and 3. Paced Auditory Serial Addition Test (PASAT).
The MSFC Z-score is calculated by creating Z-scores for each component of the MSFC and averaging them to create an overall composite score.
MSFC Z-score = (Z25-foot-walk + Z9HPT+ ZPASAT)/3. A Z-score represented the number of standard deviations participant\'s test result was higher (Z \> 0) or lower (Z \< 0) than the average test result (Z = 0) from the reference population. Higher scores indicate better outcomes.
Measured: Baseline up to 48 months
Change from baseline in Symbol Digit Modalities Test (SDMT)
The Symbol Digit Modalities Test (SDMT) assesses information processing speed and attention. It involves matching symbols to numbers according to a given key within a specified time limit.
Z-Scores are calculated. A Z-score represented the number of standard deviations participant\'s test result was higher (Z \>0) or lower (Z \<0) than the average test result (Z = 0) from the reference population. Higher scores indicate better outcomes.
Measured: Baseline up to 48 months
Change from baseline in Verbal Memory Learning Test (VMLT)
Verbal Memory Learning Test (VMLT) is an examination of verbal learning and memory by presenting a list of words to the participant multiple times and then asking them to recall as many words as possible after each presentation.
A Z-score represented the number of standard deviations participant\'s test result was higher (Z \>0) or lower (Z \<0) than the average test result (Z = 0) from the reference population. Higher scores indicate better outcomes.
Measured: Baseline up to 48 months
Change from baseline in Brief Visuospatial Memory Test (BVMT)
Brief Visuospatial Memory Test (BVMT) assesses visuospatial learning and memory. Participants are asked to recall a series of abstract designs after multiple presentations. A Z-score represented the number of standard deviations participant\'s test result was higher (Z \>0) or lower (Z \<0) than the average test result (Z = 0) from the reference population. Higher scores indicate better outcomes.
Measured: Baseline up to 48 months
Change from baseline in Montreal Cognitive Assessment (MoCA)
Montreal Cognitive Assessment (MoCA) ranges from 0 - 30, the higher the number the better the cognitive function.
Measured: Baseline up to 48 months
Change from baseline in BDI-FS/BDI II
Beck Depressions-Inventar (Fast-Score) (BDI-FS/BDI II) assesses depressive symptoms. Higher scores indicate more severe signs of depression.
Measured: Baseline up to 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2024
- Study start27 Oct 2021
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Relapsing-remitting Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Heinrich-Heine University, DuesseldorfThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Heinrich-Heine University, Duesseldorf
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Principal investigator, Univ.-Prof. Dr. med. Dr rer. nat. Sven Meuth, Heinrich-Heine University, Duesseldorf
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06586177
- Sponsor's protocol ID
- 2021-1475
- Acronym
- REBELLION-MS
- Status last verified
- Sep 2025
- First submitted
- 4 Jul 2024
- Last updated
- 18 Sep 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 40214505
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Understanding the 'Durable Effect' Concept of B-cell Modulating Therapies
- ClinicalTrials.gov ID
- NCT06586177
- Acronym / sponsor ID
- REBELLION-MS / 2021-1475
- Conditions
- Relapsing-remitting Multiple Sclerosis
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Heinrich-Heine University, DuesseldorfUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- 27 Oct 2021 (actual)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 19 Sep 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 (C1; basic cohort) | – | Drug: Anti-CD20 antibodyParticipants 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. |
| Cohort 2 (C2; in-depth cohort) | – | Drug: Anti-CD20 antibodyIn 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Age groups
- Adult
- Study population
- The study population will include RRMS patients receiving B cell modulating therapies.
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anti-CD20 antibodyStudy participants receive an anti-CD20 antibody according to the summary of product characteristics. | Drug | Cohort 1 (C1; basic cohort), Cohort 2 (C2; in-depth cohort) |
Primary outcome
Change from baseline in the peripheral immune cell profile
Time frame: Baseline up to 48 months
Immune cell subpopulations will be analyzed longitudinally by multidimensional flow cytometry [% of all living cells and mean fluorescent intensity of different cell surface markers].
Change from baseline in protein profile of the peripheral blood
Time frame: Baseline up to 48 months
Protein expression will be measured longitudinally using proteomics.
Change from baseline in TCR/BCR profile
Time frame: Baseline up to 48 months
T cell and B cell receptor profile will be measured longitudinally using BCR- and TCR-sequencing.
12 secondary outcomes
Change from baseline in Expanded Disability Status Scale (EDSS) Score
Time frame: Baseline up to 48 months
Change from baseline in Short Form Health Survey (SF-36)
Time frame: Baseline up to 48 months
Change from baseline on Magnetic Resonance Imaging (MRI)
Time frame: Baseline up to 48 months
Change from baseline in Retinal Nerve Fiber Layer thickness (RNFL)
Time frame: Baseline up to 48 months
Change from baseline in visual acuity (HCV and LCV)
Time frame: Baseline up to 48 months
Change from baseline in Fatigue Scale for Motor and Cognitive Functions (FSMC)
Time frame: Baseline up to 48 months
Change from baseline in Multiple Sclerosis Functional Composite (MSFC) Score
Time frame: Baseline up to 48 months
Change from baseline in Symbol Digit Modalities Test (SDMT)
Time frame: Baseline up to 48 months
Change from baseline in Verbal Memory Learning Test (VMLT)
Time frame: Baseline up to 48 months
Change from baseline in Brief Visuospatial Memory Test (BVMT)
Time frame: Baseline up to 48 months
Change from baseline in Montreal Cognitive Assessment (MoCA)
Time frame: Baseline up to 48 months
Change from baseline in BDI-FS/BDI II
Time frame: Baseline up to 48 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2025.
- Derived from this study: PubMed 40214505Willison 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Relapsing-remitting Multiple Sclerosis, run by Heinrich-Heine University, Duesseldorf at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Saskia Räuber, MD (+492118117889, SaskiaJanina.Raeuber@med.uni-duesseldorf.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in the peripheral immune cell profile (time frame: Baseline up to 48 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06586177, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2025.