Oral Cladribine B-cell Study

Multiple Sclerosis Clinical Trial

Official title:

Oral Cladribine B-cell Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06415864
• Other study ID #: 262436
• Status: Completed
• Start date: July 1, 2019
• Est. completion date: January 31, 2024

Study information

• Verified date: May 2024
• Source: Queen Mary University of London
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: January 31, 2024
• Est. primary completion date: January 31, 2024
• Gender: All
• Age group: N/A and older

Eligibility

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)

Related Conditions & MeSH terms

• Multiple Sclerosis

Locations

Country	Name	City	State
United Kingdom	Barts Health NHS Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
Queen Mary University of London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Compare the data of T and B cells from the CladB study versus Alemtuzumab	To compare B and T cell repertoire with a contemporary control group of alemtuzumab treated pwMS (historical data	2 years
Primary	To study B cells subsets changes	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+).	2 years
Secondary	Changes in OCBs and free immunoglobulin kappa and lambda light chain levels (FLC)	To study the effects of oral cladribine on CSF OCBs and FLC between baseline, 48kws and 96 wks	2 years
Secondary	Measure of CXCL-13 and urine markers of inflammation (neopterin)	To study the effects of oral cladribine on CSF markers of inflammation, in particular CXCL-13 and neopterin between baseline, 48kws and 96 wks	2 years
Secondary	Measure of Neurofilament light chain (NFL)	To study the effects of oral cladribine on CSF NFL between baseline, 48kws and 96 wks	2 years
Secondary	Measure of soluble CD138	o study the effects of oral cladribine on CSF sCD138 between baseline, 48kws and 96 wks	2 years
Secondary	Measure of cytokines and chemokines	o study the effects of oral cladribine on CSF cytokines and chemokines between baseline, 48kws and 96 wks	2 years