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)
Overview
- Phase
- Phase 4
- Intervention
- Fingolimod
- Conditions
- Relapsing Remitting Multiple Sclerosis
- Sponsor
- University Hospital Muenster
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- Temporal changes in the expression of CD49d
- Last Updated
- 11 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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.
Arms & Interventions
Natalizumab - Washout - 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.
Intervention: Fingolimod
Natalizumab - Washout - 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.
Intervention: Natalizumab
Outcomes
Primary Outcomes
Temporal changes in the expression of CD49d
Time Frame: 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
Time Frame: 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 Outcomes
- 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)