Predicting Disease Activity and Rebound Risk in MS Patients Treated With Sphingosine-1-phosphate Receptor Modulators (S1PRM)

NCT05828901 | Recruiting

• 1 other identifier: IM047-1034
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Sphingosine 1-Phosphate (S1P) receptor modulators (S1PRMs) are part of the evolving treatment landscape of Multiple Sclerosis (MS) immunotherapies. They target the G-protein coupled S1P receptor, among other localizations expressed at the surface of lymphocytes. Binding as a functional antagonist leads to internalization of the receptor and therefore lymphocyte sequestration in the secondary lymphoid organs. The first S1PRM approved was fingolimod. More recently newer generation S1PRMs like ozanimod have been approved, which possess differences in receptor affinities, pharmacokinetics and indications (including Secondary Progressive MS or Ulcerative Colitis). Several retrospective analyses have shown that, upon cessation of fingolimod, pronounced relapse of the MS-disease called "rebound disease activity" may occur. Indeed, these relapses, sometimes with considerable severity, take place in up to 10% of patients. The risk of rebound disease of the newer generation S1PRM are not well defined. Although of utmost importance, predictive biomarkers of treatment efficacy in general and in special circumstances, e.g. an impending rebound when S1PRM cessation is planned, are scarce. In this prospective, exploratory observational study, we aim to investigate the predictive potential of the lymphocytic S1PR1 and 5 expression prior to treatment initiation with the newer generation S1PRM ozanimod on the future disease activity ("on treatment" part). Additionally, in a post-treatment part ("off treatment"), the incidence of rebound disease and the predictive potential of the lymphocytic S1PR1 and 5 expression will be examined in patients, where ozanimod has to be stopped due to clinical reasons. T and B cells from patient blood samples obtained prior to treatment start/cessation and 3 - 6 months after start/cessation will be isolated and S1PR1 and 5 staining intensity will be assessed by flow cytometry (FACS). Clinical assessments (relapse assessment, EDSS, medical history etc.) will be performed at every visit and MRI evaluation, following our standard clinical and MRI MS protocol. MRI disease activity will serve as the primary endpoint for both study groups. The relationship between the flow cytometric staining intensity and the defined endpoints will be assessed statistically by using comparative statistical approaches and multivariable regression analysis where needed for both time points. The data collected will correlate the expression pattern of S1P receptors by T and B lymphocytes to the proxy of paraclinical activity as predictive biomarkers for disease activity on treatment and after treatment discontinuation.

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (2)

• "On treatment" MRI disease activity

  Enhancing T1 lesions or new/enlarging T2 lesions - in the re-baseline MRI (change from baseline), defined as first MRI after treatment start performed during routine clinical care

  Between 3 - 6 months after start of any new MS immunotherapy in our center compared to the previous scan

• "Off treatment" MRI disease activity

  Enhancing T1 lesions or new/enlarging T2 lesions - in the re-baseline MRI of the subsequent immunotherapy after cessation of ozanimod, performed during routine clinical care

  Between 3 - 6 months after start of any new MS drug in our center

Secondary Outcomes (4)

• "On treatment" Relapse rate

  In the first year of ozanimod treatment

• "Off treatment" Relapse rate and severity

  In the first 6 months after ozanimod cessation

• "On treatment" Disability progression

  In the first year of ozanimod treatment

• "Off treatment" Severity

  In the first 6 months after ozanimod cessation

Study Arms (2)

Relapsing Remitting Multiple Sclerosis starting Ozanimod

Other: S1PR analysis on immune cells

Relapsing Remitting Multiple Sclerosis stopping Ozanimod

Other: S1PR analysis on immune cells

Interventions

S1PR analysis on immune cells OTHER

S1P receptor 1 and 5 expression will be measured on immune cells

Relapsing Remitting Multiple Sclerosis starting Ozanimod; Relapsing Remitting Multiple Sclerosis stopping Ozanimod

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patients with the diagnosis of relapsing remitting MS (RRMS), treated at the Bern University Hospital, who start or stop ozanimod treatment as indicated per clinical routine

You may qualify if:

• Adult patients with RRMS (McDonald criteria 2017) fulfilling the Swiss medic label for ozanimod
• Written informed consent
• Adult patients with RRMS (McDonald criteria 2017) who stop ozanimod as indicated in clinical routine.
• Written informed consent

You may not qualify if:

• All vulnerable persons defined by Swiss law including, but not limited to pregnant women, prisoners etc.
• Hypersensitivity and allergy against ozanimod or tablet ingredients.
• People not understanding the ICF due to mental disabilities.
• People with insufficient German or French language skills.

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (1)

Neurology department

Bern, 3010, Switzerland

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

EDTA tube, PAXgene tube, serum

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Robert Hoepner, PD Dr. med.

  Insel Gruppe AG, University Hospital Bern

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Robert Hoepner, PD Dr. med.

CONTACT

+41316329465; robert.hoepner@insel.ch

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2023
• First Posted: April 25, 2023
• Study Start: March 27, 2023
• Primary Completion: March 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: November 14, 2024

Record last verified: 2024-11

Locations

CH (1)