Clinical trial NCT05828901: Predicting Disease Activity and Rebound Risk in MS Patients Treated With Sphingosine-1-phosphate Receptor Modulators (S1PRM)
Official title: Predicting Disease Activity and Rebound Risk in MS Patients Treated With Sphingosine-1-phosphate Receptor Modulators (S1PRM)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Multiple Sclerosis
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
First posted: 2023-04-25
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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.


Eligibility criteria: Inclusion Criteria "On treatment":

* Adult patients with RRMS (McDonald criteria 2017) fulfilling the Swiss medic label for ozanimod
* Written informed consent

Inclusion Criteria "Off treatment":

* Adult patients with RRMS (McDonald criteria 2017) who stop ozanimod as indicated in clinical routine.
* Written informed consent

Exclusion Criteria "On treatment" and "Off treatment":

* 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.

Primary outcomes:
measure: "On treatment" MRI disease activity
timeFrame: Between 3 - 6 months after start of any new MS immunotherapy in our center compared to the previous scan
measure: "Off treatment" MRI disease activity
timeFrame: Between 3 - 6 months after start of any new MS drug in our center
Secondary outcomes:
measure: "On treatment" Relapse rate
timeFrame: In the first year of ozanimod treatment
measure: "Off treatment" Relapse rate and severity
timeFrame: In the first 6 months after ozanimod cessation
measure: "On treatment" Disability progression
timeFrame: In the first year of ozanimod treatment
measure: "Off treatment" Severity
timeFrame: In the first 6 months after ozanimod cessation
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: Neurology department
Study officials:
affiliation: Insel Gruppe AG, University Hospital Bern
name: Robert Hoepner, PD Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: