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

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)

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).

Study Overview

• Status: Completed
• Conditions: Relapsing-remitting Multiple Sclerosis
• Intervention / Treatment: Drug: fingolimod

• Study Type: Interventional
• Enrollment (Actual): 133
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Altenholz-Stift, Germany, 24161
    • Novartis Investigative Site
  • Aschaffenburg, Germany, 63739
    • Novartis Investigative Site
  • Berlin, Germany, 10713
    • Novartis Investigative Site
  • Berlin, Germany, 12163
    • Novartis Investigative Site
  • Berlin, Germany, 13347
    • Novartis Investigative Site
  • Boblingen, Germany, 71032
    • Novartis Investigative Site
  • Celle, Germany, 29223
    • Novartis Investigative Site
  • Dortmund, Germany, 44137
    • Novartis Investigative Site
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Erbach, Germany, 64711
    • Novartis Investigative Site
  • Frankfurt, Germany, 60313
    • Novartis Investigative Site
  • Göttingen, Germany, 37073
    • Novartis Investigative Site
  • Jena, Germany, 07740
    • Novartis Investigative Site
  • Kiel, Germany, 24105
    • Novartis Investigative Site
  • Klingenmünster, Germany, 76889
    • Novartis Investigative Site
  • Lappersdorf, Germany, 93138
    • Novartis Investigative Site
  • Leverkusen, Germany, 51375
    • Novartis Investigative Site
  • Mönchengladbach, Germany, 41239
    • Novartis Investigative Site
  • München, Germany, 81829
    • Novartis Investigative Site
  • Neuburg an der Donau, Germany, 86633
    • Novartis Investigative Site
  • Siegen, Germany, 57076
    • Novartis Investigative Site
  • Singen, Germany, 78224
    • Novartis Investigative Site
  • Troisdorf, Germany, 53844
    • Novartis Investigative Site
  • Ulm, Germany, 89073
    • Novartis Investigative Site
  • Unterhaching, Germany, 82008
    • Novartis Investigative Site
  • Baden-Wuerttemberg
    • Ostfildern, Baden-Wuerttemberg, Germany, 73760
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Written informed consent before any assessment was performed.
2. Randomized in study CFTY720DDE01 and received at least one dose of study drug (fingolimod) and completed the study.
3. Continuous intake of fingolimod after end of study CFTY720DDE01 with a maximum treatment interruption of 3 months in total before entering this study.
4. Parallel participation at study CFTY720DDE02 (Pangaea NIS) was allowed.

Exclusion criteriat:

1. 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.
2. 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.
3. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: fingolimod; 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

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2016
• Primary Completion (Actual): November 14, 2016
• Study Completion (Actual): November 14, 2016

Study Registration Dates

• First Submitted: March 21, 2016
• First Submitted That Met QC Criteria: March 21, 2016
• First Posted (Estimate): March 25, 2016

Study Record Updates

• Last Update Posted (Actual): February 8, 2019
• Last Update Submitted That Met QC Criteria: September 6, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Biomarker; Multiple sclerosis; fingolimod; Relapsing-remitting multiple sclerosis
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Sphingosine 1 Phosphate Receptor Modulators; Fingolimod Hydrochloride
• Other Study ID Numbers: CFTY720DDE01E1