ToFingo2: Study to Assess Immune Function and MRI Disease Activity in RRMS Patients When Switching From Natalizumab to Gilenya
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 4 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: 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. |
Drug: Fingolimod
Fingolimod: 0.5 mg p.o. (o.i.d)
Other Names:
Drug: Natalizumab
Natalizumab: 300 mg i.v. (once at baseline);
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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))
- 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)
Eligibility Criteria
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.
-
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/mm3.
-
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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Universitaetsklinikum Muenster, Department of Neurology | Muenster | Germany | 48149 |
Sponsors and Collaborators
- University Hospital Muenster
- Novartis
Investigators
- Principal Investigator: Luisa Klotz, PD. Dr. med., Universitätsklinikum Muenster, Germany
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- UKM12_0037
- 2013-004616-21
- CFTY720D2415T