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Completed

NCT Number: NCT06415864

Oral Cladribine B-cell Study

To study the impact of cladribine on peripheral and intrathecal B-cell, plasma cells, T cells and Tregs

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Key information

Conditions

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

Sex eligibility

All sexes

Study type

Observational

Primary location

Barts Health NHS Trust

London, United Kingdom

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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)

Exclusion criteria

  • 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)

Treatment and study plan

Primary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

Secondary outcomes

  1. Changes in CSF of κ Free Light Chain (KFLC) From Baseline to Week 48 and Week 96

    Time frame: Baseline to 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.

  2. Change in CSF Oligoclonal Band (OCB) Positivity From Baseline to Week 48 and Week 96

    Time frame: Baseline to 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

  3. Changes in CSF of λ Free Light Chain (LFLC) Index From Baseline to Week 48 and Week 96

    Time frame: Baseline to 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.

  4. Change in CSF CXCL-13 Levels From Baseline to Week 96

    Time frame: 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.

  5. Change in Urine Neopterin Levels From Baseline to Week 96

    Time frame: 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

  6. Change in CSF Neurofilament Light Chain (NfL) Levels From Baseline to Week 96

    Time frame: Baseline to 96 weeks

    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

  7. Change in CSF Soluble CD138 Levels From Baseline to Week 96

    Time frame: 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.

  8. Changes in CSF Cytokine and Chemokine Levels From Baseline to Week 96

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Queen Mary University of London

Other

Registry information

Important dates

Study start
2019
Primary completion
2024
Study completion
2024
First posted
May 16, 2024
Registry last updated
Feb 4, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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