Long-term Effect of Fingolimod on Circulating Immunocompetent Mononuclear Cells in Patients With Multiple Sclerosis (BiobankII)
Primary Purpose
Relapsing Remitting Multiple Sclerosis
Status
Terminated
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
Fingolimod
Sponsored by
About this trial
This is an interventional treatment trial for Relapsing Remitting Multiple Sclerosis
Eligibility Criteria
Inclusion Criteria:
- Written informed consent from patients capable of giving or withholding full informed consent must be obtained before any assessment is performed in this trial.
- Male or female subjects aged 18-65 years.
- Subjects with relapsing remitting forms of MS defined by 2010 revised McDonald criteria (see Appendix).
- Patients with high disease activity despite treatment with a disease modifying therapy (≥ 1 relapse in the previous year, ≥ 9 hyperintense T2 lesions or ≥1 Gd-enhancing lesion or "non-responding" which could be defined as unchanged or increased relapse rate or ongoing severe relapses compared to previous year) or patients with rapidly evolving severe RRMS (e.g. ≥ 2 relapses with disease progression in one year and ≥ 1 Gd-enhancing lesion or with a significant increase in T2 lesions compared to a recent MRI).
- Patients with Expanded Disability Status Scale (EDSS) score of 0-6.5 (see Appendix).
- Sufficient ability to read, write, communicate and understand
Exclusion Criteria:
- Patients with a manifestation of MS other than relapsing remitting MS.
- Patients with a history of chronic disease of the immune system other than MS, which requires systemic immunosuppressive treatment, or a known immunodeficiency syndrome.
- History or presence of malignancy (other than localized basal cell carcinoma of the skin and carcinoma in situ of the cervix) in the last 5 years
- Diabetic patients with moderate or severe non-proliferative diabetic retinopathy or proliferative diabetic retinopathy and uncontrolled diabetic patients with HbA1c > 7%.
- Diagnosis of macular edema during Baseline Visit (patients with a history of macular edema will be allowed to enter the study provided that they do not have macular edema at the ophthalmic baseline visit).
- Patients with active systemic bacterial, viral or fungal infections, or known to have AIDS, Hepatitis B, Hepatitis C infection or to have positive HIV antibody, Hepatitis B surface antigen or Hepatitis C antibody tests.
- Negative for varicella-zoster virus IgG antibodies at Baseline.
- Have received any live or live attenuated vaccines (including for varicella-zoster virus or measles) within 1 month prior to baseline.
- Patients who have received total lymphoid irradiation or bone marrow transplantation.
- Patients who expect to be treated with any disease modifying drugs (DMD) during the study (i.e. IFN-β, glatiramer acetate); however no washout is needed for DMDs prior to baseline.
Sites / Locations
- Heinrich Heine Universität Düsseldorf
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Fingolimod
Arm Description
Gilenya 0,5mg per day, oral
Outcomes
Primary Outcome Measures
Reduction of CD4+ and CD8+ naïve T cells (CCR7+ CD45RA+) and central memory T cells (CCR7+CD45RA-), and an elevation of effector memory T cells (CCR7- CD45RA-) by examining the blood
The primary endpoints are the reduction of CD4+ and CD8+ naïve T cells (CCR7+ CD45RA+) and central memory T cells (CCR7+CD45RA-), and an elevation of effector memory T cells (CCR7- CD45RA-)in the blood, and to study the effect of Fingolimod on Th17 cells by studying their signature cytokines (IL-17, IL-21, IL-22) as well as signature transcription factors (ROR-gamma-t, ROR-alpha, STAT3, Runx1) in peripheral venous blood over 2 years versus baseline.
Secondary Outcome Measures
To investigate changes from baseline in B Lymphocytes, monocytes and NK cells in the blood after treatment with fingolimod
To investigate changes from baseline in B Lymphocytes, monocytes and NK cells in the blood after treatment with fingolimod. This will be assessed by studying surface markers by FACS analysis for B lymphocytes (CD19, CD20, CD69), monocytes (CD14), NK cells (CD56).
Full Information
NCT ID
NCT01755871
First Posted
December 19, 2012
Last Updated
June 8, 2016
Sponsor
Heinrich-Heine University, Duesseldorf
Collaborators
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT01755871
Brief Title
Long-term Effect of Fingolimod on Circulating Immunocompetent Mononuclear Cells in Patients With Multiple Sclerosis
Acronym
BiobankII
Official Title
The Long-term Effect of Fingolimod on Circulating Immunocompetent Mononuclear Cells in Patients With Multiple Sclerosis
Study Type
Interventional
2. Study Status
Record Verification Date
June 2015
Overall Recruitment Status
Terminated
Why Stopped
lack of recruitment
Study Start Date
January 2013 (undefined)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
February 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Heinrich-Heine University, Duesseldorf
Collaborators
Novartis Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to explore immunomodulatory and immunosuppressive mechanisms of action of fingolimod in patients with Relapsing remitting multiple Sclerosis to collect data on biomarkers after initiation of fingolimod treatment.
Detailed Description
After treatment with fingolimod the blood of the patients will be collected at different time points to examine the changes of T cells, B cells and biomarkers.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsing Remitting Multiple Sclerosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Fingolimod
Arm Type
Experimental
Arm Description
Gilenya 0,5mg per day, oral
Intervention Type
Drug
Intervention Name(s)
Fingolimod
Other Intervention Name(s)
Gilenya
Intervention Description
0,5mg Fingolimod once a day
Primary Outcome Measure Information:
Title
Reduction of CD4+ and CD8+ naïve T cells (CCR7+ CD45RA+) and central memory T cells (CCR7+CD45RA-), and an elevation of effector memory T cells (CCR7- CD45RA-) by examining the blood
Description
The primary endpoints are the reduction of CD4+ and CD8+ naïve T cells (CCR7+ CD45RA+) and central memory T cells (CCR7+CD45RA-), and an elevation of effector memory T cells (CCR7- CD45RA-)in the blood, and to study the effect of Fingolimod on Th17 cells by studying their signature cytokines (IL-17, IL-21, IL-22) as well as signature transcription factors (ROR-gamma-t, ROR-alpha, STAT3, Runx1) in peripheral venous blood over 2 years versus baseline.
Time Frame
Day 0, Day 28, Day 84, Day 168, Day 336, Day 504, Day 672 after treatment
Secondary Outcome Measure Information:
Title
To investigate changes from baseline in B Lymphocytes, monocytes and NK cells in the blood after treatment with fingolimod
Description
To investigate changes from baseline in B Lymphocytes, monocytes and NK cells in the blood after treatment with fingolimod. This will be assessed by studying surface markers by FACS analysis for B lymphocytes (CD19, CD20, CD69), monocytes (CD14), NK cells (CD56).
Time Frame
Day 0, Day 28, Day 84, Day 168, Day 336, Day 504, Day 672 after treatment
Other Pre-specified Outcome Measures:
Title
Change of the biomarkers BDNF, NGF, CNTF and LIF in the blood during treatment with fingolimod
Description
The exploratory endpoints are the change from baseline in the biomarkers BDNF, NGF, CNTF and LIF in the blood. The changes in mRNA expression and serum protein levels will be analysed in peripheral blood as a result of fingolimod treatment.
Time Frame
Day 0, Day 28, Day 84, Day 168, Day 336, Day 504, Day 672 after treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Written informed consent from patients capable of giving or withholding full informed consent must be obtained before any assessment is performed in this trial.
Male or female subjects aged 18-65 years.
Subjects with relapsing remitting forms of MS defined by 2010 revised McDonald criteria (see Appendix).
Patients with high disease activity despite treatment with a disease modifying therapy (≥ 1 relapse in the previous year, ≥ 9 hyperintense T2 lesions or ≥1 Gd-enhancing lesion or "non-responding" which could be defined as unchanged or increased relapse rate or ongoing severe relapses compared to previous year) or patients with rapidly evolving severe RRMS (e.g. ≥ 2 relapses with disease progression in one year and ≥ 1 Gd-enhancing lesion or with a significant increase in T2 lesions compared to a recent MRI).
Patients with Expanded Disability Status Scale (EDSS) score of 0-6.5 (see Appendix).
Sufficient ability to read, write, communicate and understand
Exclusion Criteria:
Patients with a manifestation of MS other than relapsing remitting MS.
Patients with a history of chronic disease of the immune system other than MS, which requires systemic immunosuppressive treatment, or a known immunodeficiency syndrome.
History or presence of malignancy (other than localized basal cell carcinoma of the skin and carcinoma in situ of the cervix) in the last 5 years
Diabetic patients with moderate or severe non-proliferative diabetic retinopathy or proliferative diabetic retinopathy and uncontrolled diabetic patients with HbA1c > 7%.
Diagnosis of macular edema during Baseline Visit (patients with a history of macular edema will be allowed to enter the study provided that they do not have macular edema at the ophthalmic baseline visit).
Patients with active systemic bacterial, viral or fungal infections, or known to have AIDS, Hepatitis B, Hepatitis C infection or to have positive HIV antibody, Hepatitis B surface antigen or Hepatitis C antibody tests.
Negative for varicella-zoster virus IgG antibodies at Baseline.
Have received any live or live attenuated vaccines (including for varicella-zoster virus or measles) within 1 month prior to baseline.
Patients who have received total lymphoid irradiation or bone marrow transplantation.
Patients who expect to be treated with any disease modifying drugs (DMD) during the study (i.e. IFN-β, glatiramer acetate); however no washout is needed for DMDs prior to baseline.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bernd Kieseier, Prof.
Organizational Affiliation
Heinrich Heine Universität Düsseldorf
Official's Role
Principal Investigator
Facility Information:
Facility Name
Heinrich Heine Universität Düsseldorf
City
Düsseldorf
State/Province
Nord-Rhein Westfahlen
ZIP/Postal Code
40225
Country
Germany
12. IPD Sharing Statement
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Long-term Effect of Fingolimod on Circulating Immunocompetent Mononuclear Cells in Patients With Multiple Sclerosis
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