## Protocol Section
### Identification Module
**NCT ID:** NCT06415864

**Brief Title:** Oral Cladribine B-cell Study

**Official Title:** Oral Cladribine B-cell Study

#### Organization Study ID Info
**ID:** 262436
#### Organization
**Class:** OTHER
**Full Name:** Queen Mary University of London
### Status Module
#### Completion Date
**Date:** 2024-01-31

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-16

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-14

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2024-01-31

**Type:** ACTUAL

#### Start Date
**Date:** 2019-07-01

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-16
**Type:** ACTUAL
**Study First Submit Date:** 2024-04-03
**Study First Submit QC Date:** 2024-05-14
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Queen Mary University of London

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**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.

### Conditions Module

**Conditions:**

- Multiple Sclerosis

**Keywords:**

- MS

### Design Module

#### Design Info

**Observational Model:** COHORT

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 10

**Type:** ACTUAL

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**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

**Label:** Cladribine (Mavenclad, Merck Serono Ltd)

### Outcomes Module

#### Other Outcomes

**Description:** To compare B and T cell repertoire with a contemporary control group of alemtuzumab treated pwMS (historical data

**Measure:** Compare the data of T and B cells from the CladB study versus Alemtuzumab

**Time Frame:** 2 years

#### Primary Outcomes

**Description:** 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+).

**Measure:** To study B cells subsets changes

**Time Frame:** 2 years

#### Secondary Outcomes

**Description:** To study the effects of oral cladribine on CSF OCBs and FLC between baseline, 48kws and 96 wks

**Measure:** Changes in OCBs and free immunoglobulin kappa and lambda light chain levels (FLC)

**Time Frame:** 2 years

**Description:** To study the effects of oral cladribine on CSF markers of inflammation, in particular CXCL-13 and neopterin between baseline, 48kws and 96 wks

**Measure:** Measure of CXCL-13 and urine markers of inflammation (neopterin)

**Time Frame:** 2 years

**Description:** To study the effects of oral cladribine on CSF NFL between baseline, 48kws and 96 wks

**Measure:** Measure of Neurofilament light chain (NFL)

**Time Frame:** 2 years

**Description:** o study the effects of oral cladribine on CSF sCD138 between baseline, 48kws and 96 wks

**Measure:** Measure of soluble CD138

**Time Frame:** 2 years

**Description:** o study the effects of oral cladribine on CSF cytokines and chemokines between baseline, 48kws and 96 wks

**Measure:** Measure of cytokines and chemokines

**Time Frame:** 2 years

### Eligibility Module

**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)

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- CHILD

- ADULT

- OLDER_ADULT

**Study Population:** Relapsing-remitting MS

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** London

**Country:** United Kingdom

**Facility:** Barts Health NHS Trust

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000020278

- Term: Demyelinating Autoimmune Diseases, CNS

- ID: D000020274

- Term: Autoimmune Diseases of the Nervous System

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000003711

- Term: Demyelinating Diseases

- ID: D000001327

- Term: Autoimmune Diseases

- ID: D000007154

- Term: Immune System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC20

- Name: Immune System Diseases

### Condition Browse Module - Browse Leaves

- ID: M15415

- Name: Sclerosis

- Relevance: LOW

- As Found: Unknown

- ID: M12060

- Name: Multiple Sclerosis

- Relevance: HIGH

- As Found: Multiple Sclerosis

- ID: M4629

- Name: Autoimmune Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M22098

- Name: Demyelinating Autoimmune Diseases, CNS

- Relevance: LOW

- As Found: Unknown

- ID: M22094

- Name: Autoimmune Diseases of the Nervous System

- Relevance: LOW

- As Found: Unknown

- ID: M6909

- Name: Demyelinating Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000009103

- Term: Multiple Sclerosis

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M19625

- Name: Cladribine

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
