Oral Cladribine B-cell Study

Queen Mary University of London

Status: Completed

Conditions: Multiple Sclerosis

Study type: Observational

Funder types: Other

Identifiers

NCT06415864

262436

Details and patient eligibility

About

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

Full 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.

Enrollment: 10 patients

Sex: All

Volunteers: No Healthy Volunteers

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)

Trial design

10 participants in 1 patient group

Cladribine (Mavenclad, Merck Serono Ltd)

Description:

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