Monthly Monitoring of Plasma NfL in Treated Relapsing-remitting Multiple Sclerosis to Detect Persistent Infraclinical Disease Activity

Official title

Monthly Monitoring of Plasma NfL in Treated RRMS to Detect Persistent Infraclinical Disease Activity

Overview

Reference MRI scan is recommended 6 months after treatment onset in patients with multiple sclerosis (MS), and follow-up scans at 12 months later to monitor subclinical activity. When monitoring treatment response in patients treated with disease modifying treatments (DMTs), the measurement of new or enlarging T2/FLAIR hyperintense lesions (NELs) is the preferred MRI method supplemented by contrast-enhancing lesions (CELs) for monitoring treatment response. However, some studies have suggested the deposition of gadolinium-based contrast agents in the basal ganglia and dentate nucleus of patients who underwent serial MRI acquisitions. Although significant clinical consequences of these deposits have not been demonstrated, further studies are required to better understand the potential long-term biological and clinical effects of gadolinium administration. To circumvent this potential risk, several recommendations suggested avoiding unnecessary use of gadolinium for follow-up scans. New sequences are also developed to replace gadolinium injection for the detection of active lesions. Moreover, MRI remains costly and time-consuming. In addition, systematic yearly MRI monitoring is not adapted to detect silent active lesions. This can delay identification of treatment failure and increase the risk of relapses and disability worsening, especially in the context of escalation therapy. Therefore, biological markers could allow more frequent analysis of disease activity and detect treatment failure earlier than classical clinical and MRI monitoring. Their use would greatly help clinicians to switch for high efficacy treatments (HET) and avoid potential relapses. Measurement of a structural axonal protein, neurofilament, in serum or plasma has shown promise as a marker of neuroaxonal injury and a measure of treatment response. In MS, cerebrospinal fluid (CSF) neurofilament-light chain (NfL) is also increased and is positively associated with MRI lesion load and disability scores and is a marker of treatment response. WThe study authors hypothesize that monthly plasma neurofilament-light chain (pNfL) monitoring can sensitively highlight subclinical (radiological disease activity) RDA by performing early MRI scans to confirm EDA and lead to timely treatment escalation. The main objective of this study is to compare the time to EDA in both arms (monthly pNfL monitoring vs. standard care with regular MRI scans), in patients with EDA.

Interventions

• Other Monthly pNfL monitoring
  Monthly pNfL monitoring from blood samples. In case of \>50% pNfL increase as compared to the mean of the 2 previous measures, an unscheduled visit with brain and spinal cord MRI will be scheduled

Primary outcome measures

• Time to evidence of disease activity between groups [Time frame: week 48]
• Time to evidence of disease activity between groups [Time frame: week 96]

Secondary outcome measures (12)

• Proportion of CELs between groups [Time frame: week 48]
• Proportion of CELs between groups [Time frame: week 96]
• Rate of clinical relapses between groups [Time frame: week 48]
• Rate of clinical relapses between groups [Time frame: week 96]
• Time to switch to high efficacy treatments [Time frame: week 48]
• Time to switch to high efficacy treatments [Time frame: week 96]
• Proportion of patients switching to high efficacy treatments between groups [Time frame: week 48]
• Proportion of patients switching to high efficacy treatments between groups [Time frame: week 96]
• Change in pNfL levels in patients experiencing relapse with active MRI in experimental group [Time frame: Upon experiencing relapse (maximum week 96)]
• Change in pNfL levels in patients experiencing acute clinical event in experimental group [Time frame: Upon experiencing an acute clinical event (maximum week 96)]
• Change in pNfL levels in patients experiencing radiological disease activity without clinical symptoms in experimental group [Time frame: Upon experiencing radiological disease activity (maximum week 96)]
• Change in pNfL levels in patients switching to high efficacy treatments [Time frame: Upon evidence of disease activity (maximum week 96)]

Eligibility criteria

Inclusion criteria

• Patient with RRMS according to 2024 McDonald's criteria.
• Less than 10 years from disease onset.
• Active RRMS (EDA) observed during the last 24 months: relapse and/or NELs and/or CELs as compared to a previous MRI performed within 24 months (± 3 months).
• Current MET (IFN, GA, TE, fumarates) for less than 24 months.
• Standard MRI follow-up scan performed less than 90 days before inclusion.
• Clinically stable disease for at least 30 days.
• Patients included in observational studies and cohorts (OFSEP, PROMISE …) will be eligible for inclusion in MoMo-NfL.
• For women with reproductive potential: negative pregnancy test at the time of inclusion and use of an effective method to avoid pregnancy for the duration of the trial.
• Patients able to adhere to the study visit schedule.
• Patient must have signed and given the consent.
• Patient affiliated or beneficiary of a health insurance plan.

Exclusion criteria

• Pregnant or breastfeeding woman.
• Patient unable to perform brain and/or spinal cord MRI scans.
• Patient not willing to perform monthly blood punctures.
• Patient treated with HET (S1P agonists, natalizumab, ocrelizumab, ofatumumab, rituximab, alemtuzumab, cladribine, mitoxantrone).
• Patient with a relapse within 6 months before inclusion.
• Patient with CELs within 3 months before inclusion.
• Patient with progressive MS.
• Patient unable to sign the consent.
• It is impossible to correctly inform the patient.
• Patient already participating in therapeutic research or in an exclusion period. The exclusion period corresponds to five half-lives (t1/2) of the experimental drug.
• Patient under judicial protection, or is an adult under guardianship.
• Female patients who are pregnant or breastfeeding or of reproductive potential who are not willing to employ effective birth control for the duration of the trial.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Other

Study locations

France · 2 centers

• CHU de Nice — Nice
• CHU de Nîmes — Nîmes

Identifiers

NCT: NCT07292480 · FINEX/2025/ET-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗