MultiSCRIPT-Cycle 1: Personalized Medicine in Multiple Sclerosis - Pragmatic Platform Trial Embedded Within the SMSC

A Multicenter, Randomized Pragmatic Platform Trial Embedded Within the Swiss Multiple Sclerosis Cohort (SMSC) on Neurofilament Light Chain Monitoring Added to Usual Care to Inform Personalized Treatment Decisions in Multiple Sclerosis

This is a randomized pragmatic clinical trial fully embedded in the Swiss Multiple Sclerosis Cohort to assess whether sNfL biomarker monitoring improves patient-relevant outcomes and care of patients with relapsing-remitting (RR)MS by either increasing the proportion of patients with no evidence of disease activity (EDA) or by improving patients' health-related quality of life.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Sclerosis, Relapsing-Remitting
• Intervention / Treatment: Diagnostic test: serum Neurofilament Filament Light chain (sNfL) monitoring

Detailed Description

The course of multiple sclerosis (MS) is highly heterogenous with a large variability in symptoms, severity and response to treatment. A large majority of persons with MS are treated with disease modifying therapies (DMTs). DMTs can dramatically reduce even almost suppress relapses and occurrence of new lesions in magnetic resonance imaging (MRI) by weakening the immune system but which in turn may cause side effects such as opportunistic infections with prolonged treatment duration and intensity of the immunosuppression.

A more personalized approach to MS therapy is urgently needed to treat patients as little as possible but as much as necessary and at the right time. Such tailored strategies cannot be made without detailed information on treatment response and disease activity. Levels sNfL, which is released in the blood following neuroaxonal damage, has been shown to be associated with future MS disease activity, disability worsening, MRI activity and treatment response. sNfL might therefore be helpful for a patient-tailored treatment adaptation (e.g., escalation or de-escalation) ensuring disease stability, fewer adverse events and better quality of life. While sNfL is increasingly used as a marker of treatment response, its use in routine care is not yet widely established.

The SMSC is an observational study across 8 Swiss leading MS centers including >1600 participants with MS with a median follow-up of >5.7 years. The MultiSCRIPT project aims to use this real-world data infrastructure to systematically evaluate patient-relevant benefits resulting from innovations in MS patient care.

MultiSCRIPT goes beyond a unique trial but aims to be a sustainable learning system in which accumulating data from successive pragmatic randomized trials (i.e., learning cycles) enable the continuous generation of new hypotheses on how treatment and care strategies can be further personalized to treat patients as little as possible but as much as necessary at the right time. By being nested within the already existing and ongoing SMSC, this research infrastructure embedded in clinical care offers an unique opportunity to efficiently conduct a nationwide real-life evaluation of new care strategies, at low costs, and fostering evaluation and direct translation of effective innovations into usual care to improve patient outcome and quality of life. MultiSCRIPT-Cycle 1 is the first learning cycle.

• Study Type: Interventional
• Enrollment (Actual): 920
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Aarau, Switzerland, CH-5001
    • Kantonsspital Aarau
  • Bern, Switzerland
    • Inselspital Bern
  • Geneva, Switzerland
    • Hôpitaux Universitaires de Genève
  • Lausanne, Switzerland
    • Centre Hospitalier Universitaire Vaudois
  • Lugano, Switzerland
    • Ospedale Regionale di Lugano, Sede Civico
  • Saint-Gall, Switzerland
    • Kantonsspital St.Gallen
  • Zürich, Switzerland
    • Universitatsspital Zurich
  • Basel Stadt
    • Basel, Basel Stadt, Switzerland, CH-4031
      • University Hospital Basel

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Diagnosis of RRMS according to the most recent McDonald criteria (2017) for at least one year
• Have already consented to take part in the SMSC
• Age 18 years old or older
• Able and willing to consent

Exclusion Criteria:

• Inclusion or planned inclusion in another clinical trial that determines the drug therapy for MS for the purpose of research as these patients are most likely not following the SMSC usual care.

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
Experimental: sNfL monitoring; 6-monthly blood draw to measure sNfL	Diagnostic test: serum Neurofilament Filament Light chain (sNfL) monitoring; the intervention consist of a blood draw and providing the sNfL information to the treating physician
No Intervention: Usual care; SMSC usual care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EDA3 (evidence of disease activity)	number of participant with a relapse or disability worsening (measured by Expanded Disability Status Scale (EDSS)) or disease activity on MRI imaging (new/enlarging T2 weighted lesions or T1 weighted contrast enhancing lesion on cranial or spinal cord MRI)	24-months
Multiple Sclerosis Quality of Life (MSQOL)-54 Instrument	The summary scores are the physical health composite summary and the mental health composite summary. A higher score indicates improved quality of life	24-months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Multiple Sclerosis Quality of Life (MSQOL)-54 Instrument	The summary scores are the physical health composite summary and the mental health composite summary. A higher score indicates improved quality of life	12-months
EDA3 (evidence of disease activity)	number of participant with a relapse or disability worsening (measured by Expanded Disability Status Scale (EDSS)) or disease activity on MRI imaging (new/enlarging T2 weighted lesions or T1 weighted contrast enhancing lesion on cranial or spinal cord MRI)	12-months
EQ-5D-5L	The EQ-5D-5L descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression and includes an overall visual analog scale	12- and 24-months
Short form 36 (SF-36)	contained in the MSQoL-54 questionnaire. The lower the score the more disability.	12- and 24-months
relapses	according to McDonald criteria	12- and 24-months
disability worsening	measured by Expanded Disability Status Scale (EDSS). The EDSS ranges from 0 to 10. The greater the level of disability, the higher is the score.	12- and 24-months
New/enlarging T2w lesions	MRI imaging	12- and 24-months
T1w contrast enhancing lesions	MRI imaging	12- and 24-months
Amount of immunosuppressive/immunomodulatory drug treatment		12- and 24-months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serious adverse events related to blood draw		up to 42-months
Mortality		up to 42-months
Adverse events related to immunosuppression		up to 42-months
Occurrence of relapses in patients previously stable	according to McDonald criteria	up to 42-months
Disability worsening in patients previously stable	measured by Expanded Disability Status Scale (EDSS). The EDSS ranges from 0 to 10. The greater the level of disability, the higher is the score.	up to 42-months

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Özgür Yaldizli, MD, University Hospital, Basel, Switzerland

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: October 10, 2023
• First Submitted That Met QC Criteria: October 17, 2023
• First Posted (Actual): October 23, 2023

Study Record Updates

• Last Update Posted (Actual): May 11, 2025
• Last Update Submitted That Met QC Criteria: May 9, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting
• Other Study ID Numbers: MultiSCRIPT-Cycle 1

Drug and device information, study documents

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