Clinical trial NCT06415864: Oral Cladribine B-cell Study
Official title: Oral Cladribine B-cell Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Multiple Sclerosis
Keywords: MS
Lead sponsor: Queen Mary University of London
Sponsor class: OTHER
First posted: 2024-05-16
Enrollment: 10
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Relapsing-remitting MS

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.

Eligibility criteria: 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)

Primary outcomes:
measure: To study B cells subsets changes
timeFrame: 2 years
Secondary outcomes:
measure: Changes in OCBs and free immunoglobulin kappa and lambda light chain levels (FLC)
timeFrame: 2 years
measure: Measure of CXCL-13 and urine markers of inflammation (neopterin)
timeFrame: 2 years
measure: Measure of Neurofilament light chain (NFL)
timeFrame: 2 years
measure: Measure of soluble CD138
timeFrame: 2 years
measure: Measure of cytokines and chemokines
timeFrame: 2 years
Other outcomes:
measure: Compare the data of T and B cells from the CladB study versus Alemtuzumab
timeFrame: 2 years
Locations:
city: London
country: United Kingdom
facility: Barts Health NHS Trust
Study officials:
References: