NCT02325440Unknown4 期
A 32-week, Monocentric, Exploratory, Single Arm Study to Assess Immune Function and MRI Disease Activity in Patients With RRMS Transferred From Previous Treatment With Natalizumab to Gilenya® (Fingolimod)
University Hospital Muenster1 个研究点 分布在 1 个国家目标入组 15 人开始时间: 2014年3月最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Temporal changes in the expression of CD49d
研究概览
简要总结
A trial in patients with relapsing remitting multiple sclerosis (RRMS)
Main objectives:
- To evaluate changes in the reconstitution of immune surveillance over time upon switching from natalizumab to fingolimod assessed by a change in the expression of CD49d.
- To evaluate changes in the migratory capacity of immune cells/peripheral blood mononuclear cells (PBMCs) upon switching from natalizumab to fingolimod in an in-vitro model of the blood-brain-barrier (BBB).
- To evaluate changes in paraclinical disease activity over time upon switching from natalizumab to fingolimod assessed by MRI (changes in Gd+, T2w lesions and DTI).
- To evaluate changes in T1w / FLAIR lesions upon switching from natalizumab to fingolimod.
详细描述
Patients are screened and must sign informed consent at visit 1. At the 2nd visit, all patients receive a baseline infusion of Natalizumab, which is followed by an 8 week washout Phase. After the washout Phase all patients receive fingolimod for 32 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent must be obtained before any assessment is performed.
- •Male and female subjects aged 18-65 yrs.
- •Subjects with RRMS, defined by 2010 rev. McDonald criteria.
- •Patients with an (EDSS) score of 0-6.0 inclusive.
- •Patients on treatment with natalizumab for ≥ 12 months prior to screening where treatment discontinuation is considered for any of the following reasons:
- •treatment duration for more than 2 years
- •positive JC virus (JCV) antibody status
- •adverse effects including hypersensitivity reactions
- •presence of anti-natalizumab neutralizing antibodies
- •any other valid medical reason
排除标准
- •Patients with a history of chronic disease of the immune system other than MS, which requires systemic immunosuppressive treatment, or a known immunodeficiency syndrome.
- •Patients with Crohn´s disease or ulcerative colitis.
- •Patients who have been treated with:
- •systemic corticosteroids or immunoglobulins within 1 month prior to baseline.
- •immunosuppressive medications such as azathioprine, cyclophosphamide or methotrexate within 3 months prior to baseline.
- •monoclonal antibodies (excluding natalizumab) within 3 months prior to baseline.
- •cladribine or mitoxantrone at any time.
- •History of malignancy of any organ system (other than cutaneous basal cell carcinoma).
- •Uncontrolled diabetes mellitus (HbA1c >7%).
- •Diagnosis of macular edema during Screening Phase.
- •Severe active infections, active chronic infection.
- •Negative for varicella-zoster virus immunoglobulin G antibodies prior to baseline.
- •Patients that received any live or live-attenuated vaccine (including varicella-zoster virus or measles) within 1 month prior to baseline.
- •Patients who have received total lymphoid irradiation or bone marrow transplantation.
- •Patients with any medically unstable condition, as assessed by the investigator.
- •Patients with certain cardiovascular conditions and/or findings in the screening ECG.
- •Patients with certain lung diseases.
- •Patients with certain hepatic conditions.
- •Patients with a screening white blood cell (WBC) count <3,500/mm3 or lymphocyte count <800/mm
- •Patients with certain neurologic/psychiatric disorders:
- •Patients unable to undergo MRI scans, including claustrophobia or history of hypersensitivity to gadolinium-diethylenetriaminepentacetate (Gd-DTPA).
- •Patients who have received an investigational drug or therapy within 180 days or 5 half-lives before baseline, whichever is longer.
- •Pregnant or nursing (lactating) women, confirmed by a positive human chorionic gonadotropin laboratory.
- •Women of child-bearing potential unless they are using effective contraception during the study and for 5 half-lives after stopping treatment. In case of use of oral contraception women should have been stable on the same medication for a minimum of 3 months before baseline.
- •History of hypersensitivity to the study drugs or to drugs of similar chemical classes.
- •Prior participation in a trial with fingolimod.
研究组 & 干预措施
Natalizumab - Washout - Fingolimod
Experimental
One experimental arm: Patients receive one final dose of natalizumab 300mg followed by an 8-week washout Phase and subsequent 32-week treatment Phase with fingolimod 0.5mg o.i.d.
干预措施: Fingolimod (Drug)
Natalizumab - Washout - Fingolimod
Experimental
One experimental arm: Patients receive one final dose of natalizumab 300mg followed by an 8-week washout Phase and subsequent 32-week treatment Phase with fingolimod 0.5mg o.i.d.
干预措施: Natalizumab (Drug)
结局指标
主要结局
Temporal changes in the expression of CD49d
时间窗: weeks: 12, 16, 20, 24, 28, 32
First Co-Primary Objective; Flow-cytometric analysis of temporal changes in the expression of CD49d of PBMCs; unit of measure: mean fluorescence intensity (MFI)
Migratory capacity of immune cells
时间窗: weeks: 12, 32
Second Co-Primary Objective; in-vitro model of the blood-brain-barrier (BBB) with subsequent flow-cytometric analysis and bead based quantification assessing temporal changes in the migratory capacity of immune cells; unit of measure: fluorescence intensity
次要结局
- MRI disease activity over time by T1w / FLAIR(weeks: 0, 8, 12, 16, 24, 32)
- MRI disease activity over time by GD+, T2w and DTI(weeks: 0, 8, 12, 16, 24, 32)
研究者
研究点 (1)
Loading locations...
相似试验
终止
4 期
Combination of Antidepressants and Fingolimod Relapsing-remitting Multiple Sclerosis (RRMS) Patients With DepressionDepressionRelapsing-remitting Multiple SclerosisNCT01436643Novartis Pharmaceuticals54
已完成
不适用
Assessing Relapse in Multiple Sclerosis (ARMS) QuestionnaireMultiple SclerosisNCT01547351Mallinckrodt103
已完成
不适用
Pharmacokinetic, Immunological and Biochemical Sample Collection and Analysis of a Tysabri Patient CohortRelapseMultiple SclerosisNCT01070719John F. Foley, MD270
招募中
不适用
Multiple Sclerosis Self Monitoring StudyMultiple SclerosisNCT06125301Amsterdam UMC, location VUmc225
已完成
3 期
An Extension Protocol for Multiple Sclerosis Patients Who Participated in Genzyme-Sponsored Studies of AlemtuzumabMultiple Sclerosis, Relapsing-RemittingNCT00930553Genzyme, a Sanofi Company1,314