Relapsing Multiple SclerosisPhase 4FLUENTNCT03257358
A Study of Immune Phenotype Biomarkers in Patients With Relapsing Multiple Sclerosis (RMS) After Treatment With 0.5mg Fingolimod
A Phase 4 study testing Fingolimod in people with Relapsing Multiple Sclerosis, run by Novartis Pharmaceuticals at 66 sites in United States.
Trial summary
A study of immune phenotype biomarkers in patients with Relapsing Multiple Sclerosis (RMS) after treatment with 0.5mg fingolimod Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsing Multiple Sclerosis
- What is being tested?
- Fingolimod
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 382 participants
- Where
- 66 sitesUnited States
- Study dates
- 19 Sep 2017to 28 Jun 2019
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
66 sites in 1 country.
66 sites in 1 country
United States66 sites
Novartis Investigative Site
Ann Arbor, Michigan, 48109
Novartis Investigative Site
Asheville, North Carolina, 28806
Novartis Investigative Site
Berkeley, California, 94705
Novartis Investigative Site
Birmingham, Alabama, 35209
Novartis Investigative Site
Boca Raton, Florida, 33482
Novartis Investigative Site
Boca Raton, Florida, 33487
Novartis Investigative Site
Charlotte, North Carolina, 28207
Novartis Investigative Site
Cleveland, Ohio, 44195
Novartis Investigative Site
Colorado Springs, Colorado, 80907
Novartis Investigative Site
Cullman, Alabama, 35058
Novartis Investigative Site
Dallas, Texas, 75246
Novartis Investigative Site
Dayton, Ohio, 45408
Novartis Investigative Site
Fair Lawn, New Jersey, 07410
Novartis Investigative Site
Falls Church, Virginia, 22043
Novartis Investigative Site
Flossmoor, Illinois, 60422
Novartis Investigative Site
Foxborough, Massachusetts, 02035
Novartis Investigative Site
Golden Valley, Minnesota, 55422
Novartis Investigative Site
Green Bay, Wisconsin, 54311
Novartis Investigative Site
Greer, South Carolina, 29650
Novartis Investigative Site
Huntington, West Virginia, 25701
Novartis Investigative Site
Jacksonville, Florida, 32209
Novartis Investigative Site
Kansas City, Kansas, 66160
Novartis Investigative Site
Kansas City, Missouri, 64111
Novartis Investigative Site
Kirkland, Washington, 98034
Novartis Investigative Site
Knoxville, Tennessee, 37922
Novartis Investigative Site
Las Vegas, Nevada, 89106
Novartis Investigative Site
Lexington, Massachusetts, 02421
Novartis Investigative Site
Livingston, New Jersey, 07039
Novartis Investigative Site
Louisville, Colorado, 80027
Novartis Investigative Site
Louisville, Kentucky, 40202
Novartis Investigative Site
Louisville, Kentucky, 40207
Novartis Investigative Site
Lutherville, Maryland, 21093
Novartis Investigative Site
Miami, Florida, 33136
Novartis Investigative Site
Milwaukee, Wisconsin, 53215
Novartis Investigative Site
Mooresville, North Carolina, 28117
Novartis Investigative Site
Mt. Pleasant, South Carolina, 29464
Novartis Investigative Site
Nashville, Tennessee, 37215
Novartis Investigative Site
Neenah, Wisconsin, 54956
Novartis Investigative Site
Ocala, Florida, 34471
Novartis Investigative Site
Oklahoma City, Oklahoma, 73102
Novartis Investigative Site
Oklahoma City, Oklahoma, 73104
Novartis Investigative Site
Owosso, Michigan, 48867
Novartis Investigative Site
Patchogue, New York, 11772
Novartis Investigative Site
Philadelphia, Pennsylvania, 19140
Novartis Investigative Site
Plainview, New York, 11803
Novartis Investigative Site
Port Charlotte, Florida, 33952
Novartis Investigative Site
Port Royal, South Carolina, 29935
Novartis Investigative Site
Portland, Oregon, 97225
Novartis Investigative Site
Raleigh, North Carolina, 27607
Novartis Investigative Site
Sacramento, California, 95817
Novartis Investigative Site
San Antonio, Texas, 78258
Novartis Investigative Site
Sarasota, Florida, 34243
Novartis Investigative Site
Savannah, Georgia, 31406
Novartis Investigative Site
Seattle, Washington, 98122
Novartis Investigative Site
Spokane, Washington, 99202
Novartis Investigative Site
St Louis, Missouri, 63131
Novartis Investigative Site
Sunrise, Florida, 33351
Novartis Investigative Site
Suwanee, Georgia, 30024
Novartis Investigative Site
Tacoma, Washington, 98405
Novartis Investigative Site
Toledo, Ohio, 43623
Novartis Investigative Site
Tucson, Arizona, 85718
Novartis Investigative Site
Vero Beach, Florida, 32960
Novartis Investigative Site
Vienna, Virginia, 22182
Novartis Investigative Site
Wellesley, Massachusetts, 02481
Novartis Investigative Site
Westerville, Ohio, 43081
Novartis Investigative Site
Winston-Salem, North Carolina, 27103
About this study
Official 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]
A study of immune phenotype biomarkers in patients with Relapsing Multiple Sclerosis (RMS) after treatment with 0.5mg fingolimod
Read the 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..
- Conditions
- Relapsing Multiple Sclerosis
- Being tested
- Fingolimod
- Keywords
- Relapsing Multiple Sclerosis, RMS, Relapsing Multiple Sclerosis (RMS), Multiple Sclerosis, MS, Multiple Sclerosis (MS), Fingolimod, FLUENT, Immune Phenotype, adult, FTY720
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FingolimodDrug
Commercially available 0.5mg hard capsules, taken orally once per day
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Other | RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day Receives: Drug: Fingolimod |
| Cohort 2 | Other | RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years Receives: Drug: Fingolimod |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline to Month 6 in CD4+ Naive T Cells (CCR7+ CD45RA+)
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.
Measured: Baseline to Month 6
Change From Baseline to Month 6 in CD4+ Central Memory T Cells (CCR7+CD45RA-CD45RO+)
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.
Measured: Baseline to Month 6
Change From Baseline to Month 6 in CD4+ Effector Memory T Cells (CCR7-CD45RA-CD45RO+)
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.
Measured: Baseline to Month 6
Change From Baseline to Month 6 in CD4+ Th1 Cells (CXCR3+)
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.
Measured: Baseline to Month 6
Change From Baseline to Month 6 in CD4+ Th2 Cells (CCR4+)
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.
Measured: Baseline to Month 6
Change From Baseline to Month 6 in CD4+ Th17 Cells (CCR6+)
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.
Measured: Baseline to Month 6
Change From Baseline to Month 6 in CD8+ Naive T Cells (CCR7+CD45RA+)
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.
Measured: Baseline to Month 6
Change From Baseline to Month 6 in CD8+ Central Memory T Cells (CCR7+CD45RA-CD45RO+)
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.
Measured: Baseline to Month 6
Change From Baseline to Month 6 in CD8+ Effector Memory T Cells (CCR7-CD45RA-CD45RO+)
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.
Measured: Baseline to Month 6
Change From Baseline to Month 6 in Naive B Lymphocytes (CD19+CD27-)
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.
Measured: Baseline to Month 6
Change From Baseline to Month 6 in Memory B Lymphocytes (CD19+CD27+)
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.
Measured: Baseline to Month 6
Change From Baseline to Month 6 in Regulatory B Lymphocytes (CD19+CD24+CD38+)
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.
Measured: Baseline to Month 6
Change From Baseline to Month 6 in Monocytes (CD14+)
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.
Measured: Baseline to Month 6
Change From Baseline to Month 6 in Neutrophils (CD16+)
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.
Measured: Baseline to Month 6
Change From Baseline to Month 6 in NK Cells (CD56+)
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.
Measured: Baseline to Month 6
Change From Baseline to Month 6 in Total CD4+ Absolute Cell Count
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.
Measured: Baseline to Month 6
Change From Baseline to Month 6 in Total CD4+ Differential Cell Count
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.
Measured: Baseline to Month 6
Change From Baseline to Month 6 in Total CD8+ Absolute Cell Count
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.
Measured: Baseline to Month 6
Change From Baseline to Month 6 in Total CD8+ Differential Cell Counts (%)
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.
Measured: Baseline to Month 6
Change From Baseline to Month 6 in Total CD19+ Absolute Cell Count
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.
Measured: Baseline to Month 6
Change From Baseline to Month 6 in Total CD19+ Differential Cell Count (%)
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.
Measured: Baseline to Month 6
Secondary outcomes (27)
Change From Baseline to Month 12 in CD4+ Naive T Cells (CCR7+CD45RA+)
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.
Measured: Baseline to Month 12
Change From Baseline to Month 12 in CD4+ Central Memory T Cells (CCR7+CD45RA-CD45RO+)
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.
Measured: Baseline to Month 12
Change From Baseline to Month 12 in CD4+ Effector Memory T Cells (CCR7-CD45RA-CD45RO+)
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.
Measured: Baseline to Month 12
Change From Baseline to Month 12 in CD4+ Th1 Cells (CXCR3+)
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.
Measured: Baseline to Month 12
Change From Baseline to Month 12 in CD4+ Th2 Cells (CCR4+)
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.
Measured: Baseline to Month 12
Change From Baseline to Month 12 in CD4+ Th17 Cells (CCR6+)
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.
Measured: Baseline to Month 12
Change From Baseline to Month 12 in CD8+ Naive T Cells (CCR7+CD45RA+)
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.
Measured: Baseline to Month 12
Change From Baseline to Month 12 in CD8+ Central Memory T Cells (CCR7+CD45RA-CD45RO+)
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.
Measured: Baseline to Month 12
Change From Baseline to Month 12 in CD8+ Effector Memory T Cells (CCR7-CD45RA-CD45RO+)
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.
Measured: Baseline to Month 12
Change From Baseline to Month 12 in Naive B Lymphocytes (CD19+CD27-)
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.
Measured: Baseline to Month 12
Change From Baseline to Month 12 in Memory B Lymphocytes (CD19+CD27+)
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.
Measured: Baseline to Month 12
Change From Baseline to Month 12 in Regulatory B Lymphocytes (CD19+CD24+CD38+)
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.
Measured: Baseline to Month 12
Change From Baseline to Month 12 in Monocytes (CD14+)
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.
Measured: Baseline to Month 12
Change From Baseline to Month 12 in Neutrophils (CD16+)
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.
Measured: Baseline to Month 12
Change From Baseline to Month 12 in NK Cells (CD56+)
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.
Measured: Baseline to Month 12
Change From Baseline to Month 12 in Total CD4+ Absolute Cell Count
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.
Measured: Baseline to Month 12
Change From Baseline to Month 12 in Total CD4+ Differential Cell Count (%)
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.
Measured: Baseline to Month 12
Change From Baseline to Month 12 in Total CD8+ Absolute Cell Count
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.
Measured: Baseline to Month 12
Change From Baseline to Month 12 in Total CD8+ Differential Cell Counts (%)
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.
Measured: Baseline to Month 12
Change From Baseline to Month 12 in Total CD19+ Absolute Cell Count
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.
Measured: Baseline to Month 12
Change From Baseline to Month 12 in Total CD19+ Differential Cell Count (%)
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.
Measured: Baseline to Month 12
Multiple Sclerosis (MS) Relapses During Treatment
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.
Measured: Baseline to Month 12
Number of Participants Who Received Steroid Treatment for MS Relapses During Treatment
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.
Measured: Baseline to Month 12
Change From Baseline in Patient Determined Disease Steps (PDDS)
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.
Measured: Baseline to Month 12
Change From Baseline in T2 Lesion Burden
Measured: Baseline to Month 12
Change From Baseline for New Gd-Enhancing T1 Lesion Count
Measured: Baseline to Month 12
Change From Baseline to Months 6 and 12 in the Anti-JCV Antibody Index (Index/Value)
Measured: Baseline to Month 6 and 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2017
- Study start19 Sep 2017
- Primary completion5 Mar 2019
- Study completion28 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Relapsing Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Two-cohort, non-randomized, open-label multicenter
- Masking
- None (open label)
- Enrolment
- 382 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03257358
- Sponsor's protocol ID
- CFTY720DUS40
- Acronym
- FLUENT
- Status last verified
- Oct 2021
- First submitted
- 18 Aug 2017
- Last updated
- 7 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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]
- ClinicalTrials.gov ID
- NCT03257358
- Acronym / sponsor ID
- FLUENT / CFTY720DUS40
- Conditions
- Relapsing Multiple Sclerosis
- Keywords
- Relapsing Multiple Sclerosis, RMS, Relapsing Multiple Sclerosis (RMS), Multiple Sclerosis, MS, Multiple Sclerosis (MS), Fingolimod, FLUENT
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 382 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 19 Sep 2017 (actual)
- Primary completion
- 5 Mar 2019 (actual)
- Study completion
- 28 Jun 2019 (actual)
- First posted
- 22 Aug 2017 (actual)
- Results
- Posted 21 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A study of immune phenotype biomarkers in patients with Relapsing Multiple Sclerosis (RMS) after treatment with 0.5mg fingolimod
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..
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Two-cohort, non-randomized, open-label multicenter
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Other | Drug: FingolimodRMS patients who were newly prescribed commercially available fingolimod 0.5mg per day |
| Cohort 2 | Other | Drug: FingolimodRMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FingolimodCommercially available 0.5mg hard capsules, taken orally once per day | Drug | Cohort 1, Cohort 2 |
Primary outcome
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.
27 secondary outcomes
Change From Baseline to Month 12 in CD4+ Naive T Cells (CCR7+CD45RA+)
Time frame: Baseline to Month 12
Change From Baseline to Month 12 in CD4+ Central Memory T Cells (CCR7+CD45RA-CD45RO+)
Time frame: Baseline to Month 12
Change From Baseline to Month 12 in CD4+ Effector Memory T Cells (CCR7-CD45RA-CD45RO+)
Time frame: Baseline to Month 12
Change From Baseline to Month 12 in CD4+ Th1 Cells (CXCR3+)
Time frame: Baseline to Month 12
Change From Baseline to Month 12 in CD4+ Th2 Cells (CCR4+)
Time frame: Baseline to Month 12
Change From Baseline to Month 12 in CD4+ Th17 Cells (CCR6+)
Time frame: Baseline to Month 12
Change From Baseline to Month 12 in CD8+ Naive T Cells (CCR7+CD45RA+)
Time frame: Baseline to Month 12
Change From Baseline to Month 12 in CD8+ Central Memory T Cells (CCR7+CD45RA-CD45RO+)
Time frame: Baseline to Month 12
Change From Baseline to Month 12 in CD8+ Effector Memory T Cells (CCR7-CD45RA-CD45RO+)
Time frame: Baseline to Month 12
Change From Baseline to Month 12 in Naive B Lymphocytes (CD19+CD27-)
Time frame: Baseline to Month 12
Change From Baseline to Month 12 in Memory B Lymphocytes (CD19+CD27+)
Time frame: Baseline to Month 12
Change From Baseline to Month 12 in Regulatory B Lymphocytes (CD19+CD24+CD38+)
Time frame: Baseline to Month 12
Change From Baseline to Month 12 in Monocytes (CD14+)
Time frame: Baseline to Month 12
Change From Baseline to Month 12 in Neutrophils (CD16+)
Time frame: Baseline to Month 12
Change From Baseline to Month 12 in NK Cells (CD56+)
Time frame: Baseline to Month 12
Change From Baseline to Month 12 in Total CD4+ Absolute Cell Count
Time frame: Baseline to Month 12
Change From Baseline to Month 12 in Total CD4+ Differential Cell Count (%)
Time frame: Baseline to Month 12
Change From Baseline to Month 12 in Total CD8+ Absolute Cell Count
Time frame: Baseline to Month 12
Change From Baseline to Month 12 in Total CD8+ Differential Cell Counts (%)
Time frame: Baseline to Month 12
Change From Baseline to Month 12 in Total CD19+ Absolute Cell Count
Time frame: Baseline to Month 12
Change From Baseline to Month 12 in Total CD19+ Differential Cell Count (%)
Time frame: Baseline to Month 12
Multiple Sclerosis (MS) Relapses During Treatment
Time frame: Baseline to Month 12
Number of Participants Who Received Steroid Treatment for MS Relapses During Treatment
Time frame: Baseline to Month 12
Change From Baseline in Patient Determined Disease Steps (PDDS)
Time frame: Baseline to Month 12
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- A Plain Language Trial Summary is available on novartisclinicaltrials.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
66 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Fingolimod in people with Relapsing Multiple Sclerosis, run by Novartis Pharmaceuticals at 66 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 66 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline to Month 6 in CD4+ Naive T Cells (CCR7+ CD45RA+) (time frame: Baseline to Month 6). The study lists 21 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2021.