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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

Tracking Information
First Submitted Date  ICMJE September 4, 2014
First Posted Date  ICMJE December 25, 2014
Last Update Posted Date December 25, 2014
Study Start Date  ICMJE March 2014
Estimated Primary Completion Date April 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 19, 2014)
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: December 19, 2014)
  • 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))
  • 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)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Assess Immune Function and MRI Disease Activity in RRMS Patients When Switching From Natalizumab to Gilenya
Official Title  ICMJE 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)
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Relapsing Remitting Multiple Sclerosis
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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.
Interventions:
  • Drug: Fingolimod
  • Drug: Natalizumab
Publications * Lohmann L, Janoschka C, Schulte-Mecklenbeck A, Klinsing S, Kirstein L, Hanning U, Wirth T, Schneider-Hohendorf T, Schwab N, Gross CC, Eveslage M, Meuth SG, Wiendl H, Klotz L. Immune Cell Profiling During Switching from Natalizumab to Fingolimod Reveals Differential Effects on Systemic Immune-Regulatory Networks and on Trafficking of Non-T Cell Populations into the Cerebrospinal Fluid-Results from the ToFingo Successor Study. Front Immunol. 2018 Jul 9;9:1560. doi: 10.3389/fimmu.2018.01560. eCollection 2018.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: December 19, 2014)
15
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2016
Estimated Primary Completion Date April 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02325440
Other Study ID Numbers  ICMJE UKM12_0037
2013-004616-21 ( EudraCT Number )
CFTY720D2415T ( Other Identifier: Novartis )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University Hospital Muenster
Study Sponsor  ICMJE University Hospital Muenster
Collaborators  ICMJE Novartis
Investigators  ICMJE
Principal Investigator: Luisa Klotz, PD. Dr. med. Universitätsklinikum Muenster, Germany
PRS Account University Hospital Muenster
Verification Date December 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP