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]
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 382
- 试验地点
- 1
- 主要终点
- Change From Baseline to Month 6 in CD4+ Naive T Cells (CCR7+ CD45RA+)
研究概览
简要总结
A study of immune phenotype biomarkers in patients with Relapsing Multiple Sclerosis (RMS) after treatment with 0.5mg fingolimod
详细描述
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..
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- 未提供
研究组 & 干预措施
Cohort 1
RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
干预措施: Fingolimod (Drug)
Cohort 2
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
干预措施: Fingolimod (Drug)
结局指标
主要结局
Change From Baseline to Month 6 in CD4+ Naive T Cells (CCR7+ CD45RA+)
时间窗: 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+)
时间窗: 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+)
时间窗: 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+)
时间窗: 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+)
时间窗: 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+)
时间窗: 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+)
时间窗: 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+)
时间窗: 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+)
时间窗: 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+)
时间窗: 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+)
时间窗: 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-)
时间窗: 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+)
时间窗: 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+)
时间窗: 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+)
时间窗: 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
时间窗: 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
时间窗: 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 (%)
时间窗: 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
时间窗: 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
时间窗: 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 (%)
时间窗: 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.
次要结局
- Change From Baseline to Months 6 and 12 in the Anti-JCV Antibody Index (Index/Value)(Baseline to Month 6 and 12)
- Change From Baseline to Month 12 in CD4+ Naive T Cells (CCR7+CD45RA+)(Baseline to Month 12)
- Change From Baseline to Month 12 in CD4+ Th17 Cells (CCR6+)(Baseline to Month 12)
- Change From Baseline to Month 12 in CD8+ Naive T Cells (CCR7+CD45RA+)(Baseline to Month 12)
- Change From Baseline to Month 12 in CD8+ Effector Memory T Cells (CCR7-CD45RA-CD45RO+)(Baseline to Month 12)
- Change From Baseline to Month 12 in Naive B Lymphocytes (CD19+CD27-)(Baseline to Month 12)
- Change From Baseline to Month 12 in Memory B Lymphocytes (CD19+CD27+)(Baseline to Month 12)
- Change From Baseline to Month 12 in Regulatory B Lymphocytes (CD19+CD24+CD38+)(Baseline to Month 12)
- Change From Baseline to Month 12 in Monocytes (CD14+)(Baseline to Month 12)
- Change From Baseline to Month 12 in CD4+ Effector Memory T Cells (CCR7-CD45RA-CD45RO+)(Baseline to Month 12)
- Change From Baseline to Month 12 in Neutrophils (CD16+)(Baseline to Month 12)
- Change From Baseline to Month 12 in NK Cells (CD56+)(Baseline to Month 12)
- Change From Baseline to Month 12 in Total CD4+ Absolute Cell Count(Baseline to Month 12)
- Change From Baseline to Month 12 in Total CD8+ Absolute Cell Count(Baseline to Month 12)
- Change From Baseline to Month 12 in Total CD19+ Absolute Cell Count(Baseline to Month 12)
- Number of Participants Who Received Steroid Treatment for MS Relapses During Treatment(Baseline to Month 12)
- Change From Baseline in Patient Determined Disease Steps (PDDS)(Baseline to Month 12)
- Change From Baseline to Month 12 in CD4+ Central Memory T Cells (CCR7+CD45RA-CD45RO+)(Baseline to Month 12)
- Change From Baseline to Month 12 in CD4+ Th1 Cells (CXCR3+)(Baseline to Month 12)
- Change From Baseline to Month 12 in CD4+ Th2 Cells (CCR4+)(Baseline to Month 12)
- Change From Baseline to Month 12 in CD8+ Central Memory T Cells (CCR7+CD45RA-CD45RO+)(Baseline to Month 12)
- Change From Baseline to Month 12 in Total CD4+ Differential Cell Count (%)(Baseline to Month 12)
- Change From Baseline to Month 12 in Total CD8+ Differential Cell Counts (%)(Baseline to Month 12)
- Multiple Sclerosis (MS) Relapses During Treatment(Baseline to Month 12)
- Change From Baseline in T2 Lesion Burden(Baseline to Month 12)
- Change From Baseline to Month 12 in Total CD19+ Differential Cell Count (%)(Baseline to Month 12)
- Change From Baseline for New Gd-Enhancing T1 Lesion Count(Baseline to Month 12)