Cladribine Tablets as an Exit Therapy Strategy (CLADREXIT)

Cladribine Tablets as an Exit Therapy Strategy: Alternative to Continuing Treatment and Plain Treatment Discontinuation in Ageing Stable RMS Patients

The objective of the study is to evaluate the effectiveness of CladT, in terms of disease stability and safety, as the last treatment option in ageing MS patients vs treatment continuation and discontinuation This observational study will use database from local cohorts (from France, Belgium, Switzerland). Patients included must meet the inclusion criteria: RRMS diagnosis for more than 10 years without secondary progression, no evidence of disease activity (no relapse, no new MRI lesion, no EDSS progression) for more than 5 years under a DMT, age≥ 45-year-old.

Analyses will be using dynamic propensity score to match patients who stopped treatment with patients who had the same probability of continuing / stopping current treatments but took CladT as exit therapy. Patients with a minimum of 24 months follow up will be included.

The investigators will ensure that CladT provide disease stability compared to treatment continuation / discontinuation in ageing MS patients by measuring:

• the percentage of patients free of relapse, and time to first relapse, defined as the appearance, recurrence, or aggravation of neurological symptoms for a period of at least 24 hours without fever.
• the percentage of patients free of EDSS progression confirmed for at least 6 months and until the end of patient follow up.
• the percentage of patients free of MRI activity, defined as new or enlarged T2 lesions compared with the previous brain MRI scan or gadolinium enhancing T1 lesions.

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Sclerosis; Relapsing Remitting Multiple Sclerosis; Secondary Progressive Multiple Sclerosis
• Intervention / Treatment: Drug: Cladribine

• Study Type: Observational
• Enrollment (Estimated): 450

Contacts and Locations

Study Locations

• France
  • Strasbourg, France, 67000
    • Service de neurologie - Hôpitaux Universitaires de Strasbourg
    • Contact: Jérôme DE SEZE; Phone Number: + 33 3 88 12 85 43
    • Principal Investigator: Kévin BIGAUT

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This is a multicentric retrospective and controlled cohort with non-inferiority analysis. Patients will be matched 1:1 using propensity score on gender, age, MS duration, time before last relapse, EDSS score, DMTs.

The study will use retrospectively collected data within the date frame from 06/30/25 to 06/30/26.

Approximately 150 patients treated with cladribine will be identified and included in this study in 7 centers: Strasbourg, Lille, Montpellier, Nimes, Liège, Pelt, Lugano.

Description

Inclusion Criteria:

• Patient ≥45-year-old with RRMS
• Disease duration ≥10 years
• No evidence of disease activity ≥5 years under DMT
• EDSS score between 0 and 6.0 included

Exclusion Criteria:

• Progressive form of MS
• Patients without DMT
• EDSS score ≥6.5

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cladribine group	Drug: Cladribine; To evaluate the clinical activity during the 2 years of follow-up in patients switching to cladribine and continuing current DMT
Continuing treatment group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the clinical activity during the 2 years of follow-up in patients switching to cladribine and continuing current DMT	Proportion of patients with relapses* and time to event during the 2 years of follow-up in patients switching to cladribine and continuing current DMT	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the clinical activity during the 2 years of follow-up in patients switching to cladribine and stopping current DMT	Proportion of patients with relapse and time to event during the 2 years of follow-up in patients switching to cladribine and stopping current DMT	2 years
To evaluate the clinical activity during the 3 years of follow-up in patients switching to cladribine and continuing current DMT	Proportion of patients with relapse and time to event during the 2 years of follow-up in patients switching to cladribine and continuing current DMT	2 years
To evaluate the radiological activity during the follow-up in patients switching to cladribine, continuing current DMT and stopping DMT	Proportion of patients with new T2 lesions on brain MRI at 1 and 2 years in patients switching to cladribine, continuing current DMT and stopping DMT	2 years
To evaluate the disability during the follow-up in patients switching to cladribine, continuing current DMT and stopping DMT	Proportion of patients with EDSS worsening** after 2 years in patients switching to cladribine, continuing current DMT and stopping DMT	2 years
To evaluate the risk of serious adverse events in patients switching to cladribine and continuing current DMT	Proportion of patients with any serious adverse events after 2 years in patients switching to cladribine and continuing current DMT	2 years

Collaborators and Investigators

• Sponsor: University Hospital, Strasbourg, France

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2025
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: March 13, 2025
• First Submitted That Met QC Criteria: March 13, 2025
• First Posted (Actual): March 20, 2025

Study Record Updates

• Last Update Posted (Actual): June 2, 2025
• Last Update Submitted That Met QC Criteria: May 27, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Chronic Disease; Disease Attributes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis, Chronic Progressive; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Cladribine
• Other Study ID Numbers: 9628 (Fred Hutch/University of Washington Cancer Consortium)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No