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NCT Number: NCT03257358

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

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

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Key information

Conditions

Relapsing Multiple Sclerosis Autoimmune Diseases Autoimmune Diseases of the Nervous System Demyelinating Autoimmune Diseases, CNS Demyelinating Diseases Immune System Diseases Multiple Sclerosis Nervous System Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Novartis Investigative Site, Birmingham, Alabama, United States

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About this study

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..

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Fingolimod

Drug

Commercially available 0.5mg hard capsules, taken orally once per day

Primary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  21. 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 outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  21. 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.

  22. 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.

  23. 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.

  24. 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.

  25. Change From Baseline in T2 Lesion Burden

    Time frame: Baseline to Month 12

  26. Change From Baseline for New Gd-Enhancing T1 Lesion Count

    Time frame: Baseline to Month 12

  27. Change From Baseline to Months 6 and 12 in the Anti-JCV Antibody Index (Index/Value)

    Time frame: Baseline to Month 6 and 12

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

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]

Acronym: FLUENT

Important dates

Study start
2017
Primary completion
2019
Study completion
2019
First posted
Aug 22, 2017
Registry last updated
Oct 7, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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