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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis (MS) - Relapsing-remitting
• Intervention / Treatment: Other: Monthly pNfL monitoring

• Study Type: Interventional
• Enrollment (Estimated): 84
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Eric Thouvenot; Phone Number: 04 66 68 32 61; Email: eric.thouvenot@chu-nimes.fr

Study Locations

• France
  • Nice, France
    • Recruiting
    • CHU de Nice
    • Contact: Christine LEBRUN FRENAY, Pr.; Email: lebrun-frenay.c@chu-nice.fr
  • Nîmes, France
    • Recruiting
    • CHU de Nîmes
    • Contact: Anissa Megzari; Phone Number: 04.66.68.42.36; Email: drc@chu-nimes.fr

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patient with RRMS according to 2017 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).
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard care
Experimental: pNfL monitoring group	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to evidence of disease activity between groups	As assessed by new relapse and/or occurrence of NELs and/or CELs on a follow-up MRI scan	week 48
Time to evidence of disease activity between groups	As assessed by new relapse and/or occurrence of NELs and/or CELs on a follow-up MRI scan	week 96

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of CELs between groups	percent of active (contrast-enhancing) lesion	week 48
Proportion of CELs between groups	percent of active (contrast-enhancing) lesion	week 96
Rate of clinical relapses between groups	percentage patients experiencing relapse	week 48
Rate of clinical relapses between groups	percentage patients experiencing relapse	week 96
Time to switch to high efficacy treatments	Days	week 48
Time to switch to high efficacy treatments	Days	week 96
Proportion of patients switching to high efficacy treatments between groups	Percentage	week 48
Proportion of patients switching to high efficacy treatments between groups	Percentage	week 96
Change in pNfL levels in patients experiencing relapse with active MRI in experimental group	pg/mL; measured using Lumipulse® G NfL Blood	Upon experiencing relapse (maximum week 96)
Change in pNfL levels in patients experiencing acute clinical event in experimental group	pg/mL; measured using Lumipulse® G NfL Blood	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	pg/mL; measured using Lumipulse® G NfL Blood	Upon experiencing radiological disease activity (maximum week 96)
Change in pNfL levels in patients switching to high efficacy treatments	pg/mL; measured using Lumipulse® G NfL Blood	Upon evidence of disease activity (maximum week 96)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Level of disability	EDSS (Extanded Disability Status Scale) score, range: 0.0-10	Baseline (Day 0)
Information processing speed impairment	CSCT (Computerized Speed Cognitive Test): score and standard deviation	Baseline (Day 0)
Manual dexterity	NHPT (Nine Hole Peg Test): time (seconds)	Baseline (Day 0)
Walking function	T25FW (Timed 25-Foot Walk); time (seconds)	Baseline (Day 0)
Patient-reported change in status	PGIC (Patient Global Impression of Change scale): score (7 points Likert scale)	Baseline (Day 0)
Patient-reported quality of life	EQ-5D-5L score (0-100)	Baseline (Day 0)
To estimate the best threshold of pNfL increase (last measure as compared to the mean of 2 previous measures) with best accuracy to detect evidence of disease activity	pNfL levels in pg/mL	week 96
Time to evidence of disease activity using optimized threshold in experimental group	Months	week 96
Correlation between basal pNfL fluctuations in patients with no evidence of disease activity and brain health questionnaire score	Brain-Q	week 96
Description of adverse events	Descriptive	week 96
Level of disability	EDSS (Extanded Disability Status Scale) score, range: 0.0-10	Week 48
Level of disability	EDSS (Extanded Disability Status Scale) score, range: 0.0-10	week 96
Information processing speed impairment	CSCT (Computerized Speed Cognitive Test): score and standard deviation	week 48
Information processing speed impairment	CSCT (Computerized Speed Cognitive Test): score and standard deviation	week 96
Manual dexterity	NHPT (Nine Hole Peg Test): time (seconds)	week 48
Manual dexterity	NHPT (Nine Hole Peg Test): time (seconds)	week 96
Walking function	T25FW (Timed 25-Foot Walk); time (seconds)	week 48
Walking function	T25FW (Timed 25-Foot Walk); time (seconds)	week 96
Patient-reported change in status	PGIC (Patient Global Impression of Change scale): score (7 points Likert scale)	Week 48
Patient-reported change in status	PGIC (Patient Global Impression of Change scale): score (7 points Likert scale)	week 96
Patient-reported quality of life	EQ-5D-5L score (0-100)	week 48
Patient-reported quality of life	EQ-5D-5L score (0-100)	week 96

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Investigators: Principal Investigator: Eric Thouvenot, Centre Hospitalier Universitaire de Nīmes

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2025
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: December 5, 2025
• First Submitted That Met QC Criteria: December 5, 2025
• First Posted (Actual): December 18, 2025

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Biomarker
• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting
• Other Study ID Numbers: FINEX/2025/ET-01

Drug and device information, study documents

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