- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02325440
Study to Assess Immune Function and MRI Disease Activity in RRMS Patients When Switching From Natalizumab to Gilenya (ToFingo2)
December 19, 2014 updated by: University Hospital Muenster
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)
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.
Study Overview
Status
Unknown
Conditions
Intervention / Treatment
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 Type
Interventional
Enrollment (Anticipated)
15
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Luisa Klotz, PD Dr. med.
- Phone Number: 00 +49 251 98029
- Email: luisa.klotz@ukmuenster.de
Study Locations
-
-
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Muenster, Germany, 48149
- Recruiting
- Universitaetsklinikum Muenster, Department of Neurology
-
Contact:
- Luisa Klotz, PD Dr. med.
- Phone Number: 52 +49 251 83444
- Email: luisa.klotz@ukmuenster.de
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Principal Investigator:
- Luisa Klotz, PD Dr. med.
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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.
|
Fingolimod: 0.5 mg p.o. (o.i.d)
Other Names:
Natalizumab: 300 mg i.v.
(once at baseline);
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
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weeks: 12, 16, 20, 24, 28, 32
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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
|
weeks: 12, 32
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
MRI disease activity over time by GD+, T2w and DTI
Time Frame: weeks: 0, 8, 12, 16, 24, 32
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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))
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weeks: 0, 8, 12, 16, 24, 32
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MRI disease activity over time by T1w / FLAIR
Time Frame: weeks: 0, 8, 12, 16, 24, 32
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Number of active (new or newly enlarging) lesions are assessed over time by MRI (T1w / FLAIR (Fluid Attenuated Inversion Recovery)
|
weeks: 0, 8, 12, 16, 24, 32
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Luisa Klotz, PD. Dr. med., Universitätsklinikum Muenster, Germany
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
March 1, 2014
Primary Completion (Anticipated)
April 1, 2016
Study Completion (Anticipated)
April 1, 2016
Study Registration Dates
First Submitted
September 4, 2014
First Submitted That Met QC Criteria
December 19, 2014
First Posted (Estimate)
December 25, 2014
Study Record Updates
Last Update Posted (Estimate)
December 25, 2014
Last Update Submitted That Met QC Criteria
December 19, 2014
Last Verified
December 1, 2014
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Nervous System Diseases
- Immune System Diseases
- Demyelinating Autoimmune Diseases, CNS
- Autoimmune Diseases of the Nervous System
- Demyelinating Diseases
- Autoimmune Diseases
- Multiple Sclerosis
- Sclerosis
- Multiple Sclerosis, Relapsing-Remitting
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Immunosuppressive Agents
- Immunologic Factors
- Sphingosine 1 Phosphate Receptor Modulators
- Natalizumab
- Fingolimod Hydrochloride
Other Study ID Numbers
- UKM12_0037
- 2013-004616-21 (EudraCT Number)
- CFTY720D2415T (Other Identifier: Novartis)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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