Oral Cladribine B-cell Study

NCT ID: NCT06415864

Last Updated: 2024-05-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

10 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-07-01

Study Completion Date

2024-01-31

Brief Summary

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

Detailed Description

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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.

Conditions

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Multiple Sclerosis

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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

No interventions assigned to this group

Eligibility Criteria

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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)
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Queen Mary University of London

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Barts Health NHS Trust

London, , United Kingdom

Site Status

Countries

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United Kingdom

Other Identifiers

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262436

Identifier Type: -

Identifier Source: org_study_id

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