Exploring the intrathecal anti-inflammatory effect of cladribine and its relationship with clinical efficacy

Exploring the intrathecal anti-inflammatory effect of cladribine and its relationship with clinical efficacy - CLAD19

Status

Active, not recruiting

Phases

Phase 4

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2018-004947-21-IT

Enrollment

Registered

2020-04-28

Start date

2019-06-26

Completion date

Unknown

Last updated

2025-01-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

highly active relapsing multiple sclerosis MedDRA version: 21.1 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Interventions

Trade Name: MAVENCLAD 6CPR 10mg Product Name: MAVENCLAD 6CPR 10 mg Pharmaceutical Form: Capsule

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: -Treatment with Cladribine when provided by the local Authority (AOUI Verona), started at least 30 days before the enrolment. -At least 2 cc of CSF and 10 cc of blood acquired before the beginning of the cladribine treatment and stored at -80°C -Male or female subject =18 years affected by highly active RRMS defined by at least two relapses in the previous year -EDSS =5.0 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: -Previous treatment with other DMT -Positive result to HBV, HCV, HIV, Quantiferon, and pregnancy test -Ongoing immunosuppressive therapy (including chronic use of steroid) -Active malignancy or history of malignancy -Evidence or suspicion of PML on Magnetic Resonance Imaging (MRI)

Design outcomes

Primary

Measure	Time frame
Main Objective: Verify whether a decrease of CSF levels of CXCL13 at the end of treatment (T24) with cladribine compared to the levels of CXCL13 before the treatment (T-3 -T-1) with cladribine is related to the achievement of “no evidence of disease activity” (NEDA).;Secondary Objective: Describe and compared the individual change in CSF levels of CXCL13 at the end of cladribine treatment Verify the decrease of CXCL13 in serum of patients treated with cladribine at the end of treatment compared to pre-treatment Describe potential changes in oligoclonal IgG bands in CSF of patients treated with cladribine at the end of treatment compared to pre-treatment Evaluate the transcriptomic profile obtained by the correspondent CSF cell pellet and identify mRNAs or gene sets whose expression is significantly associated to change in CXCL13CSF levels and disease activity after 2 years of cladribine treatment. Describe the correlations between change in the CSF levels of CXCL13 and disability progression, annual relapse rate and new WM Describe the correlations between change in the CSF levels of CXCL13 with advanced MRI parameters (new cortical lesions, n of chronic enlarging T2 lesions, global Cortical Thickness change) after 2 years of cladribine treatment;Primary end point(s): Decrement of CXCL13 expression level in NEDA group of patients with respect to no-NEDA group of patients at the end of the treatment.;Timepoint(s) of evaluation of this end point: 2 years of treatment with Cladribine	—

Measure

Time frame

Main Objective: Verify whether a decrease of CSF levels of CXCL13 at the end of treatment (T24) with cladribine compared to the levels of CXCL13 before the treatment (T-3 -T-1) with cladribine is related to the achievement of “no evidence of disease activity” (NEDA).;Secondary Objective: Describe and compared the individual change in CSF levels of CXCL13 at the end of cladribine treatment Verify the decrease of CXCL13 in serum of patients treated with cladribine at the end of treatment compared to pre-treatment Describe potential changes in oligoclonal IgG bands in CSF of patients treated with cladribine at the end of treatment compared to pre-treatment Evaluate the transcriptomic profile obtained by the correspondent CSF cell pellet and identify mRNAs or gene sets whose expression is significantly associated to change in CXCL13CSF levels and disease activity after 2 years of cladribine treatment. Describe the correlations between change in the CSF levels of CXCL13 and disability progression, annual relapse rate and new WM Describe the correlations between change in the CSF levels of CXCL13 with advanced MRI parameters (new cortical lesions, n of chronic enlarging T2 lesions, global Cortical Thickness change) after 2 years of cladribine treatment;Primary end point(s): Decrement of CXCL13 expression level in NEDA group of patients with respect to no-NEDA group of patients at the end of the treatment.;Timepoint(s) of evaluation of this end point: 2 years of treatment with Cladribine

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Secondary

Measure	Time frame
Secondary end point(s): -CXCL13 change in liquor. -CXCL13 change in serum. -Level of oligoclonal IgG bands (OCB) in CSF between pre-treatment (T-3?T-1) and T24. -Genome-wide sequencing-based expression data (pre-treatment T-3?T-1) of the two groups (NEDA or no-NEDA). -To examine the relationship between each NEDA parameters and CXCL13 expression levels these variables will be used: CXCL13 mean between the group of patients which experience at least one relapse and that without any relapse (in T-3?T-1 and in T24); EDSS change (T0-T24) and CXCL13 expression level change T-3?T-1/T24 ; WM number lesions change (T-3?T-1/T24) and CXCL13 value change T-3?T-1/T24. -Change in global Cth and in the number of chronic enlarging T2 lesions during the 2 years, change in the CSF levels of CXCL13. Finally, an unpaired t-test will be used to compare the CXCL13 mean between the group of patients that experience at least one new cortical lesion and that do not experience new cortical lesions. ;Timepoint(s) of evaluation of this end point: 2years of treatment with cladribine	—

Measure

Time frame

Secondary end point(s): -CXCL13 change in liquor. -CXCL13 change in serum. -Level of oligoclonal IgG bands (OCB) in CSF between pre-treatment (T-3?T-1) and T24. -Genome-wide sequencing-based expression data (pre-treatment T-3?T-1) of the two groups (NEDA or no-NEDA). -To examine the relationship between each NEDA parameters and CXCL13 expression levels these variables will be used: CXCL13 mean between the group of patients which experience at least one relapse and that without any relapse (in T-3?T-1 and in T24); EDSS change (T0-T24) and CXCL13 expression level change T-3?T-1/T24 ; WM number lesions change (T-3?T-1/T24) and CXCL13 value change T-3?T-1/T24. -Change in global Cth and in the number of chronic enlarging T2 lesions during the 2 years, change in the CSF levels of CXCL13. Finally, an unpaired t-test will be used to compare the CXCL13 mean between the group of patients that experience at least one new cortical lesion and that do not experience new cortical lesions. ;Timepoint(s) of evaluation of this end point: 2years of treatment with cladribine

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Countries

Italy

Contacts

Public ContactUnità Ricerca Clinica

AOUI Verona

supporto.noprofit@aovr.veneto.it+390458127043

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026