Follow up Study of Patients on Fingolimod Who Were Enrolled in the Original Biobank Study (CFTY720DDE01)

Study Overview
=================
Brief Summary
-----------------
The purpose of this single visit extension study is to explore immune status in RRMS patients treated for at least 48 months with fingolimod. Long-term changes in T cell counts will be compared to short-term changes in immune status (baseline to month 6) after treatment start with fingolimod as assessed in the original Biobank study (CFTY720DDE01).

Official Title
-----------------
Long-term Follow up of Patients With Relapsing-remitting Multiple Sclerosis Enrolled in the Multicenter, Single-arm, Open-label Biobank Study (CFTY720DDE01), to Investigate Changes in Biomarkers After 48 Months of Treatment With 0.5 mg Fingolimod (FTY720)

Conditions
-----------------
Relapsing-remitting Multiple Sclerosis

Intervention / Treatment
-----------------
* Drug: fingolimod


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent before any assessment was performed. Randomized in study CFTY720DDE01 and received at least one dose of study drug (fingolimod) and completed the study. Continuous intake of fingolimod after end of study CFTY720DDE01 with a maximum treatment interruption of 3 months in total before entering this study. Parallel participation at study CFTY720DDE02 (Pangaea NIS) was allowed. Exclusion criteriat: Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human Chorionic Gonadotropin (hCG) laboratory test. Patients with onset of an acute relapse had to postpone their evaluation until deemed stable from relapse by treating physician, but at least for 1 month since end of relapse. Patients that received immunomodulating or immunosuppressive MS treatments other than fingolimod since completion of study CFTY720DDE01 as for example: Natalizumab,Alemtuzumab, Dimethyl fumarate, Teriflunomide, intravenous Immunoglobulins,Mitoxantrone, Methotrexate, Azathioprine or experimental immunomodulating-immunosuppressive therapies.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: fingolimod<br>Patients did not receive any protocol specified treatment during this follow-up study. Patients remained on their current treatment regime (fingolimod), as determined by their regular treating physician (i.e. 0.5 mg fingolimod daily, single-arm). | Drug: fingolimod<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in T Cells Status (Decrease or Increase) at Month 48 (FAS) | Aim of trial was to was to show reduction of CD4+ and CD8+ naïve T cells (CCR7+CD45RA+), central memory T cells (CCR7+CD45RA-), central memory Th17 cells (CD4+ CCR4+ and CCR6+), and an elevation of 2 types of effector memory T cells TEM (CCR7- CD45RA-) and TEMRA (CCR7- CD45RA+) in peripheral venous blood. Changes from baseline to month 48 in biomarkers were analyzed for all patients in the FAS. | Baseline up to approximately 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Disability Progression as Measured by Expanded Disability Status Scale (EDSS) (FAS) | EDSS is a scale for assessing neurologic impairment in MS. It is a two-part system including (1) a series of scores in each of eight functional systems, and (2) the EDSS steps (ranging from 0 (normal) to 10 (death due to MS). The definition of disability progression was based on increases in EDSS from baseline and depended on the EDSS baseline value: Disability progression was defined as a 1.5 increase in EDSS from baseline in subjects with a baseline EDSS score between 0.0 and 0.5, as a 1.0 increase in EDSS from baseline in subjects with a baseline EDSS score between 1.0 and 5.0 inclusive and 0.5 increase from baseline in subjects with EDSS score > 5.0. | Baseline up to approximately 48 months | 
| Change From Baseline in Disability Progression Assessed With the Expanded Disability Status Scale (EDSS) at Month 6 and Month 48 (FAS) | EDSS is a scale for assessing neurologic impairment in MS. It is a two-part system including (1) a series of scores in each of eight functional systems, and (2) the EDSS steps (ranging from 0 (normal) to 10 (death due to MS). The definition of disability progression was based on increases in EDSS from baseline and depended on the EDSS baseline value: Disability progression was defined as a 1.5 increase in EDSS from baseline in subjects with a baseline EDSS score between 0.0 and 0.5, as a 1.0 increase in EDSS from baseline in subjects with a baseline EDSS score between 1.0 and 5.0 inclusive and 0.5 increase from baseline in subjects with EDSS score > 5.0. | Baseline, month 6 up to approximately 48 months | 
| Change in Immune Status of B Cells, Monocytes and Natural Killer Cells (NK) Cells (FAS) | Changes in immune status of B cells (CD19+, CD20+, CD69+), monocytes (CD14+) and NK cells (CD56+) were analyzed as a percentage of parent cell population (CD4+, CD8+ or total lymphocytes) by flow cytometry | Baseline up to approximately 48 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
fingolimod, Biomarker, Multiple sclerosis, Relapsing-remitting multiple sclerosis