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Study to Assess Immune Function and MRI Disease Activity in RRMS Patients When Switching From Natalizumab to Gilenya (ToFingo2)

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ClinicalTrials.gov Identifier: NCT02325440
Recruitment Status : Unknown
Verified December 2014 by University Hospital Muenster.
Recruitment status was:  Recruiting
First Posted : December 25, 2014
Last Update Posted : December 25, 2014
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Relapsing Remitting Multiple Sclerosis Drug: Fingolimod Drug: Natalizumab 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Study Start Date : March 2014
Estimated Primary Completion Date : April 2016
Estimated Study Completion Date : April 2016

Resource links provided by the National Library of Medicine


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:
  • FTY720
  • Gilenya

Drug: Natalizumab
Natalizumab: 300 mg i.v. (once at baseline);
Other Name: Tysabri




Primary Outcome Measures :
  1. 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)

  2. 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 Outcome Measures :
  1. MRI disease activity over time by GD+, T2w and DTI [ Time Frame: 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))

  2. MRI disease activity over time by T1w / FLAIR [ Time Frame: 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)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent must be obtained before any assessment is performed.
  2. Male and female subjects aged 18-65 yrs.
  3. Subjects with RRMS, defined by 2010 rev. McDonald criteria.
  4. Patients with an (EDSS) score of 0-6.0 inclusive.
  5. 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:

  1. Patients with a history of chronic disease of the immune system other than MS, which requires systemic immunosuppressive treatment, or a known immunodeficiency syndrome.
  2. Patients with Crohn´s disease or ulcerative colitis.
  3. 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.
  4. History of malignancy of any organ system (other than cutaneous basal cell carcinoma).
  5. Uncontrolled diabetes mellitus (HbA1c >7%).
  6. Diagnosis of macular edema during Screening Phase.
  7. Severe active infections, active chronic infection.
  8. Negative for varicella-zoster virus immunoglobulin G antibodies prior to baseline.
  9. Patients that received any live or live-attenuated vaccine (including varicella-zoster virus or measles) within 1 month prior to baseline.
  10. Patients who have received total lymphoid irradiation or bone marrow transplantation.
  11. Patients with any medically unstable condition, as assessed by the investigator.
  12. Patients with certain cardiovascular conditions and/or findings in the screening ECG.
  13. Patients with certain lung diseases.
  14. Patients with certain hepatic conditions.
  15. Patients with a screening white blood cell (WBC) count <3,500/mm3 or lymphocyte count <800/mm3.
  16. Patients with certain neurologic/psychiatric disorders:
  17. Patients unable to undergo MRI scans, including claustrophobia or history of hypersensitivity to gadolinium-diethylenetriaminepentacetate (Gd-DTPA).
  18. Patients who have received an investigational drug or therapy within 180 days or 5 half-lives before baseline, whichever is longer.
  19. Pregnant or nursing (lactating) women, confirmed by a positive human chorionic gonadotropin laboratory.
  20. 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.
  21. History of hypersensitivity to the study drugs or to drugs of similar chemical classes.
  22. Prior participation in a trial with fingolimod.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02325440


Contacts
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Contact: Luisa Klotz, PD Dr. med. +49 251 98029 ext 00 luisa.klotz@ukmuenster.de

Locations
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Germany
Universitaetsklinikum Muenster, Department of Neurology Recruiting
Muenster, Germany, 48149
Contact: Luisa Klotz, PD Dr. med.    +49 251 83444 ext 52    luisa.klotz@ukmuenster.de   
Principal Investigator: Luisa Klotz, PD Dr. med.         
Sponsors and Collaborators
University Hospital Muenster
Novartis
Investigators
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Principal Investigator: Luisa Klotz, PD. Dr. med. Universitätsklinikum Muenster, Germany

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University Hospital Muenster
ClinicalTrials.gov Identifier: NCT02325440     History of Changes
Other Study ID Numbers: UKM12_0037
2013-004616-21 ( EudraCT Number )
CFTY720D2415T ( Other Identifier: Novartis )
First Posted: December 25, 2014    Key Record Dates
Last Update Posted: December 25, 2014
Last Verified: December 2014
Keywords provided by University Hospital Muenster:
RRMS (relapsing remitting multiple sclerosis)
Cluster of differentiation 49d (CD49d)
immune function
disease activity
Additional relevant MeSH terms:
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Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Natalizumab
Fingolimod Hydrochloride
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents