Study to Assess Immune Function and MRI Disease Activity in RRMS Patients When Switching From Natalizumab to Gilenya
- Conditions
- Relapsing Remitting Multiple Sclerosis
- Interventions
- Registration Number
- NCT02325440
- Lead Sponsor
- University Hospital Muenster
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 15
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Written informed consent must be obtained before any assessment is performed.
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Male and female subjects aged 18-65 yrs.
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Subjects with RRMS, defined by 2010 rev. McDonald criteria.
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Patients with an (EDSS) score of 0-6.0 inclusive.
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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
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Patients with a history of chronic disease of the immune system other than MS, which requires systemic immunosuppressive treatment, or a known immunodeficiency syndrome.
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Patients with Crohn´s disease or ulcerative colitis.
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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.
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History of malignancy of any organ system (other than cutaneous basal cell carcinoma).
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Uncontrolled diabetes mellitus (HbA1c >7%).
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Diagnosis of macular edema during Screening Phase.
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Severe active infections, active chronic infection.
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Negative for varicella-zoster virus immunoglobulin G antibodies prior to baseline.
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Patients that received any live or live-attenuated vaccine (including varicella-zoster virus or measles) within 1 month prior to baseline.
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Patients who have received total lymphoid irradiation or bone marrow transplantation.
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Patients with any medically unstable condition, as assessed by the investigator.
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Patients with certain cardiovascular conditions and/or findings in the screening ECG.
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Patients with certain lung diseases.
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Patients with certain hepatic conditions.
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Patients with a screening white blood cell (WBC) count <3,500/mm3 or lymphocyte count <800/mm3.
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Patients with certain neurologic/psychiatric disorders:
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Patients unable to undergo MRI scans, including claustrophobia or history of hypersensitivity to gadolinium-diethylenetriaminepentacetate (Gd-DTPA).
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Patients who have received an investigational drug or therapy within 180 days or 5 half-lives before baseline, whichever is longer.
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Pregnant or nursing (lactating) women, confirmed by a positive human chorionic gonadotropin laboratory.
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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.
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History of hypersensitivity to the study drugs or to drugs of similar chemical classes.
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Prior participation in a trial with fingolimod.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Natalizumab - Washout - Fingolimod Natalizumab 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. Natalizumab - Washout - Fingolimod Fingolimod 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.
- Primary Outcome Measures
Name Time Method Temporal changes in the expression of CD49d 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 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
- Secondary Outcome Measures
Name Time Method MRI disease activity over time by T1w / FLAIR weeks: 0, 8, 12, 16, 24, 32 Number of active (new or newly enlarging) lesions are assessed over time by MRI (T1w / FLAIR (Fluid Attenuated Inversion Recovery)
MRI disease activity over time by GD+, T2w and DTI weeks: 0, 8, 12, 16, 24, 32 Number of active (new or newly enlarging) lesions are assessed over time by MRI (changes in Gadolinium (GD+), T2w lesions and DTI (Diffusion Tensor Imaging))
Trial Locations
- Locations (1)
Universitaetsklinikum Muenster, Department of Neurology
🇩🇪Muenster, Germany