Oral Cladribine B-cell Study

Completed

• Conditions: Multiple Sclerosis

• Registration Number: NCT06415864
• Lead Sponsor: Queen Mary University of London

Brief Summary

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:

1. To study the effects of oral cladribine on:

1. CSF OCBs and free immunoglobulin kappa and lambda light chain levels (FLC).

2. CSF markers of inflammation, in particular CXCL-13 and urine markers of inflammation (neopterin).

3. CSF markers of neuroaxonal damage, in particular free neurofilament light chains.

4. On the peripheral repertoire B-cells (immunoglobulin) and T-cells (T cell receptor) and plasma cells (soluble receptors).

2. To compare CSF OCB positivity and CSF light chain levels with a contemporary control group of alemtuzumab treated pwMS (historical data).

Tertiary:

1. To compare B and T cell repertoire with a contemporary control group of alemtuzumab treated pwMS (historical data).

2. To evaluate the effect of changes in the immune cell profile on clinical measures of disability, MRI activity and PROMS.

Study Timeline

• Study Start: 2019-07-01
• Primary Completion: 2024-01-31
• Study Completion: 2024-01-31
• Study First Submitted: 2024-04-03
• Status Verified: 2024-05
• Study First Submitted QC: 2024-05-14
• Last Update Submitted: 2024-05-14
• Study First Posted: 2024-05-16
• Last Update Posted: 2024-05-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

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)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To study B cells subsets changes	2 years	The temporal changes of memory B cells (CD19+/CD27+/IgD-/+), plasmablasts (CD19-/CD138+/CD38+) T cells (CD4/CD45RA-/+, CCR7-/+, CD8+/CD45RA-/+/CCR7-/+) and Tregs (CD4/CD8)/CD25+/CD127-/Fox3 P+), will be performed in the peripheral venous blood of pwMS with RRMS over 96w of treatment with oral cladribine, using Flow Cytometry.; These populations of cells 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 Outcome Measures

Name	Time	Method
Changes in OCBs and free immunoglobulin kappa and lambda light chain levels (FLC)	2 years	To study the effects of oral cladribine on CSF OCBs and FLC between baseline, 48kws and 96 wks
Measure of cytokines and chemokines	2 years	o study the effects of oral cladribine on CSF cytokines and chemokines between baseline, 48kws and 96 wks
Measure of Neurofilament light chain (NFL)	2 years	To study the effects of oral cladribine on CSF NFL between baseline, 48kws and 96 wks
Measure of soluble CD138	2 years	o study the effects of oral cladribine on CSF sCD138 between baseline, 48kws and 96 wks
Measure of CXCL-13 and urine markers of inflammation (neopterin)	2 years	To study the effects of oral cladribine on CSF markers of inflammation, in particular CXCL-13 and neopterin between baseline, 48kws and 96 wks

Trial Locations

Locations (1)

Barts Health NHS Trust; 🇬🇧 London, United Kingdom