Multiple SclerosisNCT06415864
Oral Cladribine B-cell Study
An observational study of Multiple Sclerosis, run by Queen Mary University of London at 1 site in United Kingdom.
Trial summary
To study the impact of cladribine on peripheral and intrathecal B-cell, plasma cells, T cells and Tregs Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Multiple Sclerosis
- Type of treatment
- Pill or oral medicine
- How many people
- 10 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Jul 2019to 31 Jan 2024
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Relapsing-remitting MS
Who may be able to join
- Patients with MS who are being treated with oral cladribine at Barts Health NHS Trust will be approached to participate in this study.
- Patients must be willing and able to undergo lumbar punctures
- Patients who are OCB positive in their CSF (previous diagnostic lumbar puncture)
Who cannot join
- Ineligible for oral cladribine under NHS England prescribing guidelines and those participating in MAGNIFY-MS study (cladribine tablets in active MS)
- Unsuitable to have a lumbar puncture, for example spinal deformity, tethered cord syndrome or the use of aspirin or anticoagulants, and those unable to comply with study requirements, including frequency of visits and lumbar punctures.
- Presence of comorbidities in which the administration of cladribine is contraindicated.
- Abnormal baseline investigations (WBC<3 x 10*9/l, lymphocytes <1.0 x 10*9/l, neutrophil count <1.5 x 10*9/l, platelet count <100 x 10*9, haemoglobin <110g/l, LFT>/3x upper limit of normal of site reference ranges, potassium <2.8mmol/l or >5.5mmol/l, sodium <125 mmol/l, creatinine >130 umol/l)
Trial locations and contacts
1 site in 1 country.
About this study
To study the impact of cladribine on peripheral and intrathecal B-cell, plasma cells, T cells and Tregs
Read the detailed description
Primary: To quantify the temporal changes of memory B cells (CD19+/CD27+/IgD-/+), plasmablasts (CD19-/CD138+/CD38+) and T cells (CD4/CD45RA-/+, CCR7-/+, CD8+/CD45RA-/+/CCR7-/+), Tregs (CD4/CD8)/CD25+/CD127-/Fox3 P+) in the peripheral venous blood of pwMS with RRMS over 96w of treatment with oral cladribine.
These will be compared to the populations of non-memory or class-switched B cells (immature/transitional B cells CD10+/CD38+/CD19+, immature regulatory B cells CD10+/CD38+/CD19+/CD24+/IL-10+, mature B cells CD10-/CD38+/CD19+).
Secondary:
- To study the effects of oral cladribine on:
- CSF OCBs and free immunoglobulin kappa and lambda light chain levels (FLC).
- CSF markers of inflammation, in particular CXCL-13 and urine markers of inflammation (neopterin).
- CSF markers of neuroaxonal damage, in particular free neurofilament light chains.
- On the peripheral repertoire B-cells (immunoglobulin) and T-cells (T cell receptor) and plasma cells (soluble receptors).
- To compare CSF OCB positivity and CSF light chain levels with a contemporary control group of alemtuzumab treated pwMS (historical data).
Tertiary:
- To compare B and T cell repertoire with a contemporary control group of alemtuzumab treated pwMS (historical data).
- To evaluate the effect of changes in the immune cell profile on clinical measures of disability, MRI activity and PROMS.
- Conditions
- Multiple Sclerosis
- Keywords
- MS
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Cladribine (Mavenclad, Merck Serono Ltd) | In the summary of product characteristics the recommended cumulative dose is 3.5 mg/kg body weight over 2 years, taken as 1 treatment course of 1.75 mg/kg per year. Each treatment course consists of 2 treatment weeks, 1 at the beginning of the first month and 1 at the beginning of the second month of the respective treatment year. Each treatment week consists of 4 or 5 days on which a patient takes 10 mg or 20 mg (1 or 2 tablets) as a single daily dose, depending on body weight |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in Class-switched Memory B Cells From Baseline to Week 96 nh
Percent change from baseline to Week 96 in class-switched memory B cells (CD19+/CD27+/IgD-) in participants with RRMS treated with oral cladribine.
Measured: Baseline to week 96
Percent Change in Non Class-switched Memory B Cells From Baseline to Week 96
Percent change from baseline to Week 96 in non class-switched memory B cells (CD19+/CD27+/IgD+) in participants with RRMS treated with oral cladribine.
Measured: Baseline to week 96
Percent Change in Plasmablast From Baseline to Week 96
Percent change from baseline to Week 96 in plasmablasts (CD19+/CD27+/CD38+) in participants with RRMS treated with oral cladribine.
Measured: Baseline to week 96
Percent Change in Transitional B Cells From Baseline to Week 96
Percent change from baseline to Week 96 in transitional B cells (CD19+ IgD+ CD10+ CD27-) in participants with RRMS treated with oral cladribine.
Measured: Baseline to week 96
Percent Change in Regulatory B Cells From Baseline to Week 96
Percent change from baseline to Week 96 in regulatory B cells (CD19+/CD24+/CD38+) in participants with RRMS treated with oral cladribine.
Measured: Baseline to week 96
Percent Change in CD4+ Central Memory T Cells From Baseline to Week 96
Percent change from baseline to Week 96 in CD4+ central memory T cells (CD45RA- CCR7+) in participants with RRMS treated with oral cladribine.
Measured: Baseline to week 96
Percent Change in CD4+ Naive T Cells From Baseline to Week 96
Percent change from baseline to Week 96 in CD4+ naive T cells (CD45RA+ CCR7+) in participants with RRMS treated with oral cladribine.
Measured: Baseline to week 96
Percent Change in CD4+ TEMRA Cells From Baseline to Week 96
Percent change from baseline to Week 96 in CD4+ TEMRA cells (CD45RA+ CCR7-) in participants with RRMS treated with oral cladribine.
Measured: Baseline to week 96
Percent Change in CD4+ Effector Memory T Cells From Baseline to Week 96
Percent change from baseline to Week 96 in CD4+ effector memory T cells (CD45RA- CCR7-) in participants with RRMS treated with oral cladribine.
Measured: Baseline to week 96
Percent Change in CD8+ Central Memory T Cells From Baseline to Week 96
Percent change from baseline to Week 96 in CD8+ central memory T cells (CD45RA- CCR7+) in participants with RRMS treated with oral cladribine.
Measured: Baseline to week 96
Percent Change in CD8+ Naive T Cells From Baseline to Week 96
Percent change from baseline to Week 96 in CD8+ naive T cells (CD45RA+ CCR7+) in participants with RRMS treated with oral cladribine.
Measured: Baseline to week 96
Percent Change in CD8+ TEMRA Cells From Baseline to Week 96
Percent change from baseline to Week 96 in CD8+ TEMRA cells (CD45RA+ CCR7-) in participants with RRMS treated with oral cladribine.
Measured: Baseline to week 96
Percent Change in CD8+ TEM Cells From Baseline to Week 96
Percent change from baseline to Week 96 in CD8+ effector memory T cells (CD45RA- CCR7-) in participants with RRMS treated with oral cladribine.
Measured: Baseline to week 96
Percent Change in Regulatory T Cells From Baseline to Week 96
Percent change from baseline to Week 96 in regulatory T cells (CD4+ CD25+ FOXP3+) in participants with RRMS treated with oral cladribine.
Measured: Baseline to week 96
Secondary outcomes (8)
Changes in CSF of κ Free Light Chain (KFLC) From Baseline to Week 48 and Week 96
The CSF κ Free Light Chain (KFLC) Index and λ Free Light Chain (LFLC) Index were measured at baseline, Week 48, and Week 96. KFLC and LFLC concentrations in cerebrospinal fluid and serum were obtained using Optilite. The KFLC Index and LFLC Index were calculated as (CSF FLC / serum FLC) ÷ (CSF albumin / serum albumin). These indices provide quantitative measures of intrathecal free light chain synthesis. Values are continuous laboratory measurements and do not use a score or scale.
Measured: Baseline to week 96
Change in CSF Oligoclonal Band (OCB) Positivity From Baseline to Week 48 and Week 96
CSF and matched serum samples were analysed for IgG oligoclonal bands using isoelectric focusing followed by immunoblotting. OCB positivity was defined as ≥1 IgG band present in CSF but absent in serum (CSF-restricted bands). Reported values include the number of OCB-positive and OCB-negative participants at each time point (baseline, Week 48, Week 96). Higher values indicate increased intrathecal IgG synthesis
Measured: Baseline to week 96
Changes in CSF of λ Free Light Chain (LFLC) Index From Baseline to Week 48 and Week 96
The CSF κ Free Light Chain (KFLC) Index and λ Free Light Chain (LFLC) Index were measured at baseline, Week 48, and Week 96. KFLC and LFLC concentrations in cerebrospinal fluid and serum were obtained using Optilite. The KFLC Index and LFLC Index were calculated as (CSF FLC / serum FLC) ÷ (CSF albumin / serum albumin). These indices provide quantitative measures of intrathecal free light chain synthesis. Values are continuous laboratory measurements and do not use a score or scale.
Measured: Baseline to week 96
Change in CSF CXCL-13 Levels From Baseline to Week 96
CXCL-13 concentrations in cerebrospinal fluid (CSF) were measured at baseline, Week 48, and Week 96 using immunoassay methods. Values are continuous laboratory measurements and are reported numerically (mean and standard deviation). No scoring system or clinical scale applies.
Measured: Baseline to week 96
Change in Urine Neopterin Levels From Baseline to Week 96
Urine neopterin concentrations were measured at baseline, Week 48, and Week 96 using immunoassay methods. Values are continuous laboratory measurements and are reported numerically (mean and standard deviation). No scoring system or clinical scale applied
Measured: Baseline to week 96
Change in CSF Neurofilament Light Chain (NfL) Levels From Baseline to Week 96
CSF neurofilament light chain (NfL) concentrations were measured at baseline, Week 48, and Week 96 using immunoassay methods. NfL is reported as a continuous laboratory value. Results are presented as numerical measurements (mean and standard deviation). No clinical scoring system or scale applies
Measured: Baseline to 96 weeks
Change in CSF Soluble CD138 Levels From Baseline to Week 96
Soluble CD138 concentrations in cerebrospinal fluid (CSF) were measured at baseline, Week 48, and Week 96 using immunoassay methods. Values are continuous laboratory measurements and are reported numerically (mean and standard deviation). No clinical scoring system or scale applies.
Measured: Baseline to week 96
Changes in CSF Cytokine and Chemokine Levels From Baseline to Week 96
Cerebrospinal fluid (CSF) cytokines and chemokines were measured at baseline, Week 48, and Week 96 using immunoassays. Analytes included IFN-γ, IL-10, IL-12p70, IL-13, IL-1β, IL-2, IL-4, IL-5, IL-8, and TNF-α. Values are continuous laboratory measurements and are reported numerically (mean and standard deviation). No clinical scoring system or scale applies. Results for each analyte are presented in separate rows of the results table.
Measured: Baseline to week 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2024
- Study start1 Jul 2019
- Primary completion31 Jan 2024
- Study completion31 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- 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
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Queen Mary University of London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06415864
- Sponsor's protocol ID
- 262436
- Status last verified
- Feb 2026
- First submitted
- 3 Apr 2024
- Last updated
- 4 Feb 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Oral Cladribine B-cell Study
- ClinicalTrials.gov ID
- NCT06415864
- Acronym / sponsor ID
- 262436
- Conditions
- Multiple Sclerosis
- Keywords
- MS
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Queen Mary University of LondonUniversity, hospital or other
- Study start
- 1 Jul 2019 (actual)
- Primary completion
- 31 Jan 2024 (actual)
- Study completion
- 31 Jan 2024 (actual)
- First posted
- 16 May 2024 (actual)
- Results
- Posted 4 Feb 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To study the impact of cladribine on peripheral and intrathecal B-cell, plasma cells, T cells and Tregs
Detailed description
Primary: To quantify the temporal changes of memory B cells (CD19+/CD27+/IgD-/+), plasmablasts (CD19-/CD138+/CD38+) and T cells (CD4/CD45RA-/+, CCR7-/+, CD8+/CD45RA-/+/CCR7-/+), Tregs (CD4/CD8)/CD25+/CD127-/Fox3 P+) in the peripheral venous blood of pwMS with RRMS over 96w of treatment with oral cladribine.
These will be compared to the populations of non-memory or class-switched B cells (immature/transitional B cells CD10+/CD38+/CD19+, immature regulatory B cells CD10+/CD38+/CD19+/CD24+/IL-10+, mature B cells CD10-/CD38+/CD19+).
Secondary:
- To study the effects of oral cladribine on:
- CSF OCBs and free immunoglobulin kappa and lambda light chain levels (FLC).
- CSF markers of inflammation, in particular CXCL-13 and urine markers of inflammation (neopterin).
- CSF markers of neuroaxonal damage, in particular free neurofilament light chains.
- On the peripheral repertoire B-cells (immunoglobulin) and T-cells (T cell receptor) and plasma cells (soluble receptors).
- To compare CSF OCB positivity and CSF light chain levels with a contemporary control group of alemtuzumab treated pwMS (historical data).
Tertiary:
- To compare B and T cell repertoire with a contemporary control group of alemtuzumab treated pwMS (historical data).
- To evaluate the effect of changes in the immune cell profile on clinical measures of disability, MRI activity and PROMS.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cladribine (Mavenclad, Merck Serono Ltd) | – | –In the summary of product characteristics the recommended cumulative dose is 3.5 mg/kg body weight over 2 years, taken as 1 treatment course of 1.75 mg/kg per year. Each treatment course consists of 2 treatment weeks, 1 at the beginning of the first month and 1 at the beginning of the second month of the respective treatment year. Each treatment week consists of 4 or 5 days on which a patient takes 10 mg or 20 mg (1 or 2 tablets) as a single daily dose, depending on body weight |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Relapsing-remitting MS
Key inclusion criteria (3 listed)
- Patients with MS who are being treated with oral cladribine at Barts Health NHS Trust will be approached to participate in this study.
- Patients must be willing and able to undergo lumbar punctures
- Patients who are OCB positive in their CSF (previous diagnostic lumbar puncture)
Key exclusion criteria (4 listed)
- Ineligible for oral cladribine under NHS England prescribing guidelines and those participating in MAGNIFY-MS study (cladribine tablets in active MS)
- Unsuitable to have a lumbar puncture, for example spinal deformity, tethered cord syndrome or the use of aspirin or anticoagulants, and those unable to comply with study requirements, including frequency of visits and lumbar punctures.
- Presence of comorbidities in which the administration of cladribine is contraindicated.
- Abnormal baseline investigations (WBC<3 x 10*9/l, lymphocytes <1.0 x 10*9/l, neutrophil count <1.5 x 10*9/l, platelet count <100 x 10*9, haemoglobin <110g/l, LFT>/3x upper limit of normal of site reference ranges, potassium <2.8mmol/l or >5.5mmol/l, sodium <125 mmol/l, creatinine >130 umol/l)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Percent Change in Class-switched Memory B Cells From Baseline to Week 96 nh
Time frame: Baseline to week 96
Percent change from baseline to Week 96 in class-switched memory B cells (CD19+/CD27+/IgD-) in participants with RRMS treated with oral cladribine.
Percent Change in Non Class-switched Memory B Cells From Baseline to Week 96
Time frame: Baseline to week 96
Percent change from baseline to Week 96 in non class-switched memory B cells (CD19+/CD27+/IgD+) in participants with RRMS treated with oral cladribine.
Percent Change in Plasmablast From Baseline to Week 96
Time frame: Baseline to week 96
Percent change from baseline to Week 96 in plasmablasts (CD19+/CD27+/CD38+) in participants with RRMS treated with oral cladribine.
Percent Change in Transitional B Cells From Baseline to Week 96
Time frame: Baseline to week 96
Percent change from baseline to Week 96 in transitional B cells (CD19+ IgD+ CD10+ CD27-) in participants with RRMS treated with oral cladribine.
Percent Change in Regulatory B Cells From Baseline to Week 96
Time frame: Baseline to week 96
Percent change from baseline to Week 96 in regulatory B cells (CD19+/CD24+/CD38+) in participants with RRMS treated with oral cladribine.
Percent Change in CD4+ Central Memory T Cells From Baseline to Week 96
Time frame: Baseline to week 96
Percent change from baseline to Week 96 in CD4+ central memory T cells (CD45RA- CCR7+) in participants with RRMS treated with oral cladribine.
Percent Change in CD4+ Naive T Cells From Baseline to Week 96
Time frame: Baseline to week 96
Percent change from baseline to Week 96 in CD4+ naive T cells (CD45RA+ CCR7+) in participants with RRMS treated with oral cladribine.
Percent Change in CD4+ TEMRA Cells From Baseline to Week 96
Time frame: Baseline to week 96
Percent change from baseline to Week 96 in CD4+ TEMRA cells (CD45RA+ CCR7-) in participants with RRMS treated with oral cladribine.
Percent Change in CD4+ Effector Memory T Cells From Baseline to Week 96
Time frame: Baseline to week 96
Percent change from baseline to Week 96 in CD4+ effector memory T cells (CD45RA- CCR7-) in participants with RRMS treated with oral cladribine.
Percent Change in CD8+ Central Memory T Cells From Baseline to Week 96
Time frame: Baseline to week 96
Percent change from baseline to Week 96 in CD8+ central memory T cells (CD45RA- CCR7+) in participants with RRMS treated with oral cladribine.
Percent Change in CD8+ Naive T Cells From Baseline to Week 96
Time frame: Baseline to week 96
Percent change from baseline to Week 96 in CD8+ naive T cells (CD45RA+ CCR7+) in participants with RRMS treated with oral cladribine.
Percent Change in CD8+ TEMRA Cells From Baseline to Week 96
Time frame: Baseline to week 96
Percent change from baseline to Week 96 in CD8+ TEMRA cells (CD45RA+ CCR7-) in participants with RRMS treated with oral cladribine.
Percent Change in CD8+ TEM Cells From Baseline to Week 96
Time frame: Baseline to week 96
Percent change from baseline to Week 96 in CD8+ effector memory T cells (CD45RA- CCR7-) in participants with RRMS treated with oral cladribine.
Percent Change in Regulatory T Cells From Baseline to Week 96
Time frame: Baseline to week 96
Percent change from baseline to Week 96 in regulatory T cells (CD4+ CD25+ FOXP3+) in participants with RRMS treated with oral cladribine.
8 secondary outcomes
Changes in CSF of κ Free Light Chain (KFLC) From Baseline to Week 48 and Week 96
Time frame: Baseline to week 96
Change in CSF Oligoclonal Band (OCB) Positivity From Baseline to Week 48 and Week 96
Time frame: Baseline to week 96
Changes in CSF of λ Free Light Chain (LFLC) Index From Baseline to Week 48 and Week 96
Time frame: Baseline to week 96
Change in CSF CXCL-13 Levels From Baseline to Week 96
Time frame: Baseline to week 96
Change in Urine Neopterin Levels From Baseline to Week 96
Time frame: Baseline to week 96
Change in CSF Neurofilament Light Chain (NfL) Levels From Baseline to Week 96
Time frame: Baseline to 96 weeks
Change in CSF Soluble CD138 Levels From Baseline to Week 96
Time frame: Baseline to week 96
Changes in CSF Cytokine and Chemokine Levels From Baseline to Week 96
Time frame: Baseline to week 96
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
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 Multiple Sclerosis, run by Queen Mary University of London at 1 site in United Kingdom.
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: finished, as of the sponsor's last update on 4 Feb 2026. 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 United Kingdom. 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?
Yes. Results are posted in the registry (first posted 4 Feb 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change in Class-switched Memory B Cells From Baseline to Week 96 nh (time frame: Baseline to week 96). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Feb 2026.