A Study of Immune Phenotype Biomarkers in Patients With Relapsing Multiple Sclerosis (RMS) After Treatment With 0.5mg Fingolimod

Overview

A study of immune phenotype biomarkers in patients with Relapsing Multiple Sclerosis (RMS) after treatment with 0.5mg fingolimod

Full Title of Study: “A 12-Month, Prospective, Multicenter, Two-cohort, Nonrandomized, Open-label Study in Adult Patients With Relapsing Multiple Sclerosis (RMS), to Investigate Changes in Immune Phenotype Biomarkers After Treatment With 0.5mg Fingolimod [FLUENT]”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Basic Science
    • Masking: None (Open Label)
  • Study Primary Completion Date: March 5, 2019

Detailed Description

This study used a 2-cohort, nonrandomized, open-label, multicenter design. Cohort 1: The first cohort was to be comprised of approximately 200 patients with RMS, who were newly prescribed commercially available fingolimod 0.5 mg/day. Cohort 2: The second cohort was to be comprised of approximately 200 RMS patients who had been on commercially available fingolimod 0.5 mg/day continuously without interruption of treatment for at least ≥ 2 years. Patients from both cohorts were recruited simultaneously from up to 125 MS centers in the United States. Both cohorts ran concurrently. The study consisted of 2 periods: Screening (up to 4 weeks) and Treatment period from Baseline (end of screening period considered as Day 1) up to 12 months with visits conducted at 3,6 and 12 months with a 14 day follow-up post treatment..

Interventions

  • Drug: Fingolimod
    • Commercially available 0.5mg hard capsules, taken orally once per day

Arms, Groups and Cohorts

  • Other: Cohort 1
    • RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
  • Other: Cohort 2
    • RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years

Clinical Trial Outcome Measures

Primary Measures

  • Change From Baseline to Month 6 in CD4+ Naive T Cells (CCR7+ CD45RA+)
    • Time Frame: Baseline to Month 6
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 6 in CD4+ Central Memory T Cells (CCR7+CD45RA-CD45RO+)
    • Time Frame: Baseline to Month 6
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 6 in CD4+ Effector Memory T Cells (CCR7-CD45RA-CD45RO+)
    • Time Frame: Baseline to Month 6
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 6 in CD4+ Th1 Cells (CXCR3+)
    • Time Frame: Baseline to Month 6
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 6 in CD4+ Th2 Cells (CCR4+)
    • Time Frame: Baseline to Month 6
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 6 in CD4+ Th17 Cells (CCR6+)
    • Time Frame: Baseline to Month 6
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 6 in CD8+ Naive T Cells (CCR7+CD45RA+)
    • Time Frame: Baseline to Month 6
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 6 in CD8+ Central Memory T Cells (CCR7+CD45RA-CD45RO+)
    • Time Frame: Baseline to Month 6
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 6 in CD8+ Effector Memory T Cells (CCR7-CD45RA-CD45RO+)
    • Time Frame: Baseline to Month 6
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 6 in Naive B Lymphocytes (CD19+CD27-)
    • Time Frame: Baseline to Month 6
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 6 in Memory B Lymphocytes (CD19+CD27+)
    • Time Frame: Baseline to Month 6
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 6 in Regulatory B Lymphocytes (CD19+CD24+CD38+)
    • Time Frame: Baseline to Month 6
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 6 in Monocytes (CD14+)
    • Time Frame: Baseline to Month 6
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 6 in Neutrophils (CD16+)
    • Time Frame: Baseline to Month 6
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 6 in NK Cells (CD56+)
    • Time Frame: Baseline to Month 6
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 6 in Total CD4+ Absolute Cell Count
    • Time Frame: Baseline to Month 6
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 6 in Total CD4+ Differential Cell Count
    • Time Frame: Baseline to Month 6
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 6 in Total CD8+ Absolute Cell Count
    • Time Frame: Baseline to Month 6
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 6 in Total CD8+ Differential Cell Counts (%)
    • Time Frame: Baseline to Month 6
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 6 in Total CD19+ Absolute Cell Count
    • Time Frame: Baseline to Month 6
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 6 in Total CD19+ Differential Cell Count (%)
    • Time Frame: Baseline to Month 6
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.

Secondary Measures

  • Change From Baseline to Month 12 in CD4+ Naive T Cells (CCR7+CD45RA+)
    • Time Frame: Baseline to Month 12
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 12 in CD4+ Central Memory T Cells (CCR7+CD45RA-CD45RO+)
    • Time Frame: Baseline to Month 12
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 12 in CD4+ Effector Memory T Cells (CCR7-CD45RA-CD45RO+)
    • Time Frame: Baseline to Month 12
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 12 in CD4+ Th1 Cells (CXCR3+)
    • Time Frame: Baseline to Month 12
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 12 in CD4+ Th2 Cells (CCR4+)
    • Time Frame: Baseline to Month 12
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 12 in CD4+ Th17 Cells (CCR6+)
    • Time Frame: Baseline to Month 12
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 12 in CD8+ Naive T Cells (CCR7+CD45RA+)
    • Time Frame: Baseline to Month 12
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 12 in CD8+ Central Memory T Cells (CCR7+CD45RA-CD45RO+)
    • Time Frame: Baseline to Month 12
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 12 in CD8+ Effector Memory T Cells (CCR7-CD45RA-CD45RO+)
    • Time Frame: Baseline to Month 12
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 12 in Naive B Lymphocytes (CD19+CD27-)
    • Time Frame: Baseline to Month 12
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 12 in Memory B Lymphocytes (CD19+CD27+)
    • Time Frame: Baseline to Month 12
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 12 in Regulatory B Lymphocytes (CD19+CD24+CD38+)
    • Time Frame: Baseline to Month 12
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 12 in Monocytes (CD14+)
    • Time Frame: Baseline to Month 12
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 12 in Neutrophils (CD16+)
    • Time Frame: Baseline to Month 12
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 12 in NK Cells (CD56+)
    • Time Frame: Baseline to Month 12
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 12 in Total CD4+ Absolute Cell Count
    • Time Frame: Baseline to Month 12
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 12 in Total CD4+ Differential Cell Count (%)
    • Time Frame: Baseline to Month 12
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 12 in Total CD8+ Absolute Cell Count
    • Time Frame: Baseline to Month 12
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 12 in Total CD8+ Differential Cell Counts (%)
    • Time Frame: Baseline to Month 12
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 12 in Total CD19+ Absolute Cell Count
    • Time Frame: Baseline to Month 12
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Change From Baseline to Month 12 in Total CD19+ Differential Cell Count (%)
    • Time Frame: Baseline to Month 12
    • Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
  • Multiple Sclerosis (MS) Relapses During Treatment
    • Time Frame: Baseline to Month 12
    • A relapse is defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (<37.5°C) or infection.
  • Number of Participants Who Received Steroid Treatment for MS Relapses During Treatment
    • Time Frame: Baseline to Month 12
    • A relapse is defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (<37.5°C) or infection.
  • Change From Baseline in Patient Determined Disease Steps (PDDS)
    • Time Frame: Baseline to Month 12
    • PDDS scoring ranges 0 to 8. 0 = Normal; 1 = Mild disability; 2 = Moderate disability; 3 = Gait disability; 4 = Early cane; 5 = Late cane; 6 = Bilateral support; 7 = Wheelchair/scooter; 8 = Bedridden.
  • Change From Baseline in T2 Lesion Burden
    • Time Frame: Baseline to Month 12
  • Change From Baseline for New Gd-Enhancing T1 Lesion Count
    • Time Frame: Baseline to Month 12
  • Change From Baseline to Months 6 and 12 in the Anti-JCV Antibody Index (Index/Value)
    • Time Frame: Baseline to Month 6 and 12

Participating in This Clinical Trial

Inclusion Criteria

  • Diagnosis of relapsing forms of Multiple Sclerosis – Patients who started commercially prescribed fingolimod therapy 0.5mg per day OR patients already on commercially prescribed fingolimod 0.5mg per day continuously for ≥ 2 years Exclusion Criteria (per USPI): – Patients who in the last 6 months experienced myocardial infarction, unstable angina, stroke, transient ischemic stroke, decompensated heart failure requiring hospitalization or Class III/IV heart failure – History or presence of Mobitz Type II second-degree or third-degree atrioventricular block or sick sinus syndrome, unless patient had a functioning pacemaker – Baseline QTc interval ≥ 500 msec – Treatment with Class Ia or Class III anti-arrhythmic drugs – Patients who had a hypersensitivity reaction to fingolimod or any of the excipients

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Novartis Pharmaceuticals
  • Provider of Information About this Clinical Study
    • Sponsor

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