Clinical trial NCT03257358: A Study of Immune Phenotype Biomarkers in Patients With Relapsing Multiple Sclerosis (RMS) After Treatment With 0.5mg Fingolimod
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]
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Relapsing Multiple Sclerosis
Keywords: Relapsing Multiple Sclerosis
RMS
Relapsing Multiple Sclerosis (RMS)
Multiple Sclerosis
MS
Multiple Sclerosis (MS)
Fingolimod
FLUENT
Immune Phenotype
adult
FTY720
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-08-22
Enrollment: 382
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two-cohort, non-randomized, open-label multicenter
Primary purpose: BASIC_SCIENCE

Brief summary: 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..

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline to Month 6 in CD4+ Naive T Cells (CCR7+ CD45RA+)
timeFrame: Baseline to Month 6
measure: Change From Baseline to Month 6 in CD4+ Central Memory T Cells (CCR7+CD45RA-CD45RO+)
timeFrame: Baseline to Month 6
measure: Change From Baseline to Month 6 in CD4+ Effector Memory T Cells (CCR7-CD45RA-CD45RO+)
timeFrame: Baseline to Month 6
measure: Change From Baseline to Month 6 in CD4+ Th1 Cells (CXCR3+)
timeFrame: Baseline to Month 6
measure: Change From Baseline to Month 6 in CD4+ Th2 Cells (CCR4+)
timeFrame: Baseline to Month 6
measure: Change From Baseline to Month 6 in CD4+ Th17 Cells (CCR6+)
timeFrame: Baseline to Month 6
measure: Change From Baseline to Month 6 in CD8+ Naive T Cells (CCR7+CD45RA+)
timeFrame: Baseline to Month 6
measure: Change From Baseline to Month 6 in CD8+ Central Memory T Cells (CCR7+CD45RA-CD45RO+)
timeFrame: Baseline to Month 6
measure: Change From Baseline to Month 6 in CD8+ Effector Memory T Cells (CCR7-CD45RA-CD45RO+)
timeFrame: Baseline to Month 6
measure: Change From Baseline to Month 6 in Naive B Lymphocytes (CD19+CD27-)
timeFrame: Baseline to Month 6
measure: Change From Baseline to Month 6 in Memory B Lymphocytes (CD19+CD27+)
timeFrame: Baseline to Month 6
measure: Change From Baseline to Month 6 in Regulatory B Lymphocytes (CD19+CD24+CD38+)
timeFrame: Baseline to Month 6
measure: Change From Baseline to Month 6 in Monocytes (CD14+)
timeFrame: Baseline to Month 6
measure: Change From Baseline to Month 6 in Neutrophils (CD16+)
timeFrame: Baseline to Month 6
measure: Change From Baseline to Month 6 in NK Cells (CD56+)
timeFrame: Baseline to Month 6
measure: Change From Baseline to Month 6 in Total CD4+ Absolute Cell Count
timeFrame: Baseline to Month 6
measure: Change From Baseline to Month 6 in Total CD4+ Differential Cell Count
timeFrame: Baseline to Month 6
measure: Change From Baseline to Month 6 in Total CD8+ Absolute Cell Count
timeFrame: Baseline to Month 6
measure: Change From Baseline to Month 6 in Total CD8+ Differential Cell Counts (%)
timeFrame: Baseline to Month 6
measure: Change From Baseline to Month 6 in Total CD19+ Absolute Cell Count
timeFrame: Baseline to Month 6
measure: Change From Baseline to Month 6 in Total CD19+ Differential Cell Count (%)
timeFrame: Baseline to Month 6
Secondary outcomes:
measure: Change From Baseline to Month 12 in CD4+ Naive T Cells (CCR7+CD45RA+)
timeFrame: Baseline to Month 12
measure: Change From Baseline to Month 12 in CD4+ Central Memory T Cells (CCR7+CD45RA-CD45RO+)
timeFrame: Baseline to Month 12
measure: Change From Baseline to Month 12 in CD4+ Effector Memory T Cells (CCR7-CD45RA-CD45RO+)
timeFrame: Baseline to Month 12
measure: Change From Baseline to Month 12 in CD4+ Th1 Cells (CXCR3+)
timeFrame: Baseline to Month 12
measure: Change From Baseline to Month 12 in CD4+ Th2 Cells (CCR4+)
timeFrame: Baseline to Month 12
measure: Change From Baseline to Month 12 in CD4+ Th17 Cells (CCR6+)
timeFrame: Baseline to Month 12
measure: Change From Baseline to Month 12 in CD8+ Naive T Cells (CCR7+CD45RA+)
timeFrame: Baseline to Month 12
measure: Change From Baseline to Month 12 in CD8+ Central Memory T Cells (CCR7+CD45RA-CD45RO+)
timeFrame: Baseline to Month 12
measure: Change From Baseline to Month 12 in CD8+ Effector Memory T Cells (CCR7-CD45RA-CD45RO+)
timeFrame: Baseline to Month 12
measure: Change From Baseline to Month 12 in Naive B Lymphocytes (CD19+CD27-)
timeFrame: Baseline to Month 12
measure: Change From Baseline to Month 12 in Memory B Lymphocytes (CD19+CD27+)
timeFrame: Baseline to Month 12
measure: Change From Baseline to Month 12 in Regulatory B Lymphocytes (CD19+CD24+CD38+)
timeFrame: Baseline to Month 12
measure: Change From Baseline to Month 12 in Monocytes (CD14+)
timeFrame: Baseline to Month 12
measure: Change From Baseline to Month 12 in Neutrophils (CD16+)
timeFrame: Baseline to Month 12
measure: Change From Baseline to Month 12 in NK Cells (CD56+)
timeFrame: Baseline to Month 12
measure: Change From Baseline to Month 12 in Total CD4+ Absolute Cell Count
timeFrame: Baseline to Month 12
measure: Change From Baseline to Month 12 in Total CD4+ Differential Cell Count (%)
timeFrame: Baseline to Month 12
measure: Change From Baseline to Month 12 in Total CD8+ Absolute Cell Count
timeFrame: Baseline to Month 12
measure: Change From Baseline to Month 12 in Total CD8+ Differential Cell Counts (%)
timeFrame: Baseline to Month 12
measure: Change From Baseline to Month 12 in Total CD19+ Absolute Cell Count
timeFrame: Baseline to Month 12
measure: Change From Baseline to Month 12 in Total CD19+ Differential Cell Count (%)
timeFrame: Baseline to Month 12
measure: Multiple Sclerosis (MS) Relapses During Treatment
timeFrame: Baseline to Month 12
measure: Number of Participants Who Received Steroid Treatment for MS Relapses During Treatment
timeFrame: Baseline to Month 12
measure: Change From Baseline in Patient Determined Disease Steps (PDDS)
timeFrame: Baseline to Month 12
measure: Change From Baseline in T2 Lesion Burden
timeFrame: Baseline to Month 12
measure: Change From Baseline for New Gd-Enhancing T1 Lesion Count
timeFrame: Baseline to Month 12
measure: Change From Baseline to Months 6 and 12 in the Anti-JCV Antibody Index (Index/Value)
timeFrame: Baseline to Month 6 and 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Cullman
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Tucson
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Berkeley
country: United States
facility: Novartis Investigative Site
state: California
city: Sacramento
country: United States
facility: Novartis Investigative Site
state: California
city: Colorado Springs
country: United States
facility: Novartis Investigative Site
state: Colorado
city: Louisville
country: United States
facility: Novartis Investigative Site
state: Colorado
city: Boca Raton
country: United States
facility: Novartis Investigative Site
state: Florida
city: Boca Raton
country: United States
facility: Novartis Investigative Site
state: Florida
city: Jacksonville
country: United States
facility: Novartis Investigative Site
state: Florida
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Ocala
country: United States
facility: Novartis Investigative Site
state: Florida
city: Port Charlotte
country: United States
facility: Novartis Investigative Site
state: Florida
city: Sarasota
country: United States
facility: Novartis Investigative Site
state: Florida
city: Sunrise
country: United States
facility: Novartis Investigative Site
state: Florida
city: Vero Beach
country: United States
facility: Novartis Investigative Site
state: Florida
city: Savannah
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Suwanee
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Flossmoor
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Kansas City
country: United States
facility: Novartis Investigative Site
state: Kansas
city: Louisville
country: United States
facility: Novartis Investigative Site
state: Kentucky
city: Louisville
country: United States
facility: Novartis Investigative Site
state: Kentucky
city: Lutherville
country: United States
facility: Novartis Investigative Site
state: Maryland
city: Foxboro
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Lexington
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Wellesley
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Owosso
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Golden Valley
country: United States
facility: Novartis Investigative Site
state: Minnesota
city: Kansas City
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Saint Louis
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Las Vegas
country: United States
facility: Novartis Investigative Site
state: Nevada
city: Fair Lawn
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Livingston
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Patchogue
country: United States
facility: Novartis Investigative Site
state: New York
city: Plainview
country: United States
facility: Novartis Investigative Site
state: New York
city: Asheville
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Charlotte
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Mooresville
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Raleigh
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Cleveland
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Dayton
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Toledo
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Westerville
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Oklahoma City
country: United States
facility: Novartis Investigative Site
state: Oklahoma
city: Oklahoma City
country: United States
facility: Novartis Investigative Site
state: Oklahoma
city: Portland
country: United States
facility: Novartis Investigative Site
state: Oregon
city: Philadelphia
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Greer
country: United States
facility: Novartis Investigative Site
state: South Carolina
city: Mount Pleasant
country: United States
facility: Novartis Investigative Site
state: South Carolina
city: Port Royal
country: United States
facility: Novartis Investigative Site
state: South Carolina
city: Knoxville
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Nashville
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Dallas
country: United States
facility: Novartis Investigative Site
state: Texas
city: San Antonio
country: United States
facility: Novartis Investigative Site
state: Texas
city: Falls Church
country: United States
facility: Novartis Investigative Site
state: Virginia
city: Vienna
country: United States
facility: Novartis Investigative Site
state: Virginia
city: Kirkland
country: United States
facility: Novartis Investigative Site
state: Washington
city: Seattle
country: United States
facility: Novartis Investigative Site
state: Washington
city: Spokane
country: United States
facility: Novartis Investigative Site
state: Washington
city: Tacoma
country: United States
facility: Novartis Investigative Site
state: Washington
city: Huntington
country: United States
facility: Novartis Investigative Site
state: West Virginia
city: Green Bay
country: United States
facility: Novartis Investigative Site
state: Wisconsin
city: Milwaukee
country: United States
facility: Novartis Investigative Site
state: Wisconsin
city: Neenah
country: United States
facility: Novartis Investigative Site
state: Wisconsin
Study officials:
References: