Effect of Oral Cladribine Tablets on Immune Synapse Molecules in Relapsing Multiple Sclerosis Patients: A 12‑Month Comparative Study

The primary objective is to evaluate changes in immune synapse molecules in treatment‑naïve relapsing multiple sclerosis patients receiving cladribine tablets compared with healthy volunteers after 12 months of therapy, thereby elucidating the mechanistic effects of the drug on immune cell interaction. Secondary objectives are to:

• assess alterations in immune synapse molecules at 6 months of treatment;
• determine the impact of cladribine on relapse frequency;
• evaluate changes in disease‑related disability;
• characterize modifications in radiological disease activity;
• investigate the association between immune synapse expression and clinical outcomes;
• investigate the association between immune synapse expression and magnetic resonance imaging findings.

The trial enrolled adult participants aged 18 to 50 years, including both females and males. Subjects comprised individuals diagnosed with relapsing‑remitting Multiple Sclerosis who were treatment‑naïve, as well as healthy volunteers without neurological disease. Selection required a confirmed diagnosis of RRMS, a comprehensive diagnostic workup within six months prior to enrolment, and prescription of cladribine according to the approved label in Greece. All participants provided written informed consent. Lifestyle factors such as diet, physical activity, or habits were not specified as selection criteria. The sponsor did not provide information on the total number of participants enrolled.

The study evaluates the effect of cladribine tablets on the immune synapse in adults with relapsing‑remitting multiple sclerosis over a 12‑month treatment period. Eligible participants are treatment‑naïve patients aged 18–50 years who meet defined diagnostic criteria and receive MAVENCLAD 10 mg tablets according to the approved SmPC. After a screening visit to confirm eligibility, baseline assessments are performed, followed by administration of the study drug and scheduled follow‑up visits at 6 and 12 months to collect blood samples, clinical scores (ARR, EDSS, T25FW, 9HPT), and MRI data. A final end‑of‑study visit at month 12 completes the observation. primary endpoint is the change from baseline in expression of co‑stimulatory and adhesion molecules comprising the immune synapse at 12 months; secondary endpoints include analogous 6‑month changes, relapse rate, disability progression, functional test outcomes, lesion counts, NEDA‑3/ME‑DA‑3 status, and correlations with imaging and clinical parameters. Participant involvement lasts approximately one year, with the possibility of early termination for withdrawal of consent, emergence of exclusion criteria, serious adverse events, or inability to adhere to the protocol. The trial is classified as a low‑interventional, controlled study conducted between February 2026 and February 2028.

The investigational product is MAVENCLAD 10 mg tablets containing the active substance cladribine. The tablets are administered orally with a total dose of 20 mg per administration. The study protocol specifies the dosing schedule, and the tablets are taken according to that schedule throughout the treatment period.

Adherence to the dosing regimen is monitored by study staff through pill counts, patient diaries, and scheduled clinic visits. Any deviations from the prescribed schedule are recorded and assessed for impact on study outcomes.

Efficacy will be evaluated by quantifying the change in the expression of the co‑stimulatory and adhesion molecules that constitute the immune synapse within the relevant adaptive and innate immune cell subpopulations. Assessments will be performed at baseline and after 12 months of treatment, and the primary analysis will compare the 12‑month values to baseline.

Secondary efficacy parameters include the same immune synapse expression change at 6 months, the change in annualized relapse rate (ARR) over the first year, the change in Expanded Disability Status Scale score (EDSS), the change in Timed 25‑Foot Walk time (T25FW), and the change in Nine‑Hole Peg Test time (9HPT). Radiological outcomes comprise the number of T1‑weighted lesions (gadolinium‑enhancing and black holes), the number of T2‑weighted lesions (total, new or enlarging), and the number of cortical and subcortical lesions (CUA) at the end of year 1. Additionally, the proportion of patients achieving No Evidence of Disease Activity (NEDA-3) and the proportion achieving Minimal Evidence of Disease Activity (MEDA-3) will be determined. Correlative analyses will explore relationships between changes in immune synapse expression and both clinical outcomes and MRI findings at year 1.

All laboratory measurements will be conducted using validated immunophenotyping assays on peripheral blood samples collected at the specified timepoints. Clinical scales (EDSS, T25FW, 9HPT) and relapse data will be recorded by trained investigators according to standard protocols. MRI assessments will follow established imaging sequences and lesion counting criteria. Data will be analyzed by comparing each endpoint at the designated follow‑up visits to baseline values, employing appropriate statistical methods for longitudinal data.