Trial Outcomes & Findings for Fingolimod Effect on Cytokine and Chemokine Levels (NCT NCT02373098)
NCT ID: NCT02373098
Last Updated: 2019-09-30
Results Overview
Blood samples were taken at baseline and measurements were performed before treatment of fingolimod.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
126 participants
Primary outcome timeframe
Baseline
Results posted on
2019-09-30
Participant Flow
60 healthy controls and 66 Relapsing-remitting multiple sclerosis (RRMS) patients were enrolled in the study. The healthy volunteers had only Visit 1 (Day 0). Fingolimod 0.5 mg capsule once daily was given on the same day to RRMS patients. Patients were treated for 6 months with 2 additional visits, Visit 2 and Visit 3.
Participant milestones
| Measure |
FTY720
Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od.
|
Healthy Volunteers
The healthy volunteers had only Visit 1 (Day 0) and served as control group for cytokine/chemokine measurements
|
|---|---|---|
|
Overall Study
STARTED
|
66
|
60
|
|
Overall Study
COMPLETED
|
54
|
60
|
|
Overall Study
NOT COMPLETED
|
12
|
0
|
Reasons for withdrawal
| Measure |
FTY720
Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od.
|
Healthy Volunteers
The healthy volunteers had only Visit 1 (Day 0) and served as control group for cytokine/chemokine measurements
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Protocol Violation
|
3
|
0
|
|
Overall Study
Withdrawal by Subject
|
5
|
0
|
|
Overall Study
Adverse Event
|
3
|
0
|
Baseline Characteristics
Fingolimod Effect on Cytokine and Chemokine Levels
Baseline characteristics by cohort
| Measure |
FTY720
n=66 Participants
Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od.
|
Healthy Volunteers
n=60 Participants
The healthy volunteers had only Visit 1 (Day 0) and served as control group for cytokine/chemokine measurements
|
Total
n=126 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
35.75 Years
STANDARD_DEVIATION 8.20 • n=5 Participants
|
34.73 Years
STANDARD_DEVIATION 9.62 • n=7 Participants
|
35.27 Years
STANDARD_DEVIATION 8.89 • n=5 Participants
|
|
Sex: Female, Male
Female
|
46 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
86 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
40 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Turkish
|
66 Participants
n=5 Participants
|
60 Participants
n=7 Participants
|
126 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: BaselinePopulation: Intent to treat
Blood samples were taken at baseline and measurements were performed before treatment of fingolimod.
Outcome measures
| Measure |
Healthy Controls
n=60 Participants
Healthy volunteers had only Visit 1 (day 0) when serum and whole blood samples were taken.
|
FTY720
n=66 Participants
Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od.
|
Visit 3
Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od at visit 3
|
Visit 3
Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od at visit 3
|
|---|---|---|---|---|
|
Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA
CCL5 (RANTES)
|
212.26 pg/ml
Standard Error 22.48
|
404.31 pg/ml
Standard Error 55.189
|
—
|
—
|
|
Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA
IL-17A
|
1.15 pg/ml
Standard Error 0.03
|
1.06 pg/ml
Standard Error 0.029
|
—
|
—
|
|
Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA
CXCL13
|
110.8 pg/ml
Standard Error 22.3
|
139.68 pg/ml
Standard Error 46.631
|
—
|
—
|
|
Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA
IL6
|
0.88 pg/ml
Standard Error 0.324
|
66.53 pg/ml
Standard Error 65.411
|
—
|
—
|
|
Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA
IL8
|
3.25 pg/ml
Standard Error 0.47
|
3.57 pg/ml
Standard Error 0.553
|
—
|
—
|
|
Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA
IL13
|
0.49 pg/ml
Standard Error 0.331
|
0.3 pg/ml
Standard Error 0.15
|
—
|
—
|
|
Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA
IL23
|
1.29 pg/ml
Standard Error 0.552
|
3.04 pg/ml
Standard Error 0.924
|
—
|
—
|
|
Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA
VLA4
|
1.17 pg/ml
Standard Error 0.396
|
0.58 pg/ml
Standard Error 0.201
|
—
|
—
|
|
Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA
CXCL10=IP-10 (CXCR3 ligand)
|
16.09 pg/ml
Standard Error 1.76
|
18.18 pg/ml
Standard Error 2.405
|
—
|
—
|
|
Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA
CCL2=MCP-1
|
52.88 pg/ml
Standard Error 4.281
|
62.89 pg/ml
Standard Error 8.42
|
—
|
—
|
|
Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA
IL4
|
2.02 pg/ml
Standard Error 0.077
|
2.36 pg/ml
Standard Error 0.149
|
—
|
—
|
|
Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA
TNF alpha
|
1.1 pg/ml
Standard Error 0.195
|
1.06 pg/ml
Standard Error 0.1
|
—
|
—
|
|
Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA
IL22
|
22.36 pg/ml
Standard Error 0.581
|
22.41 pg/ml
Standard Error 0.547
|
—
|
—
|
PRIMARY outcome
Timeframe: BaselinePopulation: Analysis was done in the healthy volunteers and RRMS patients.
baseline peripheral blood flow cytometric analysis in study participants
Outcome measures
| Measure |
Healthy Controls
n=60 Participants
Healthy volunteers had only Visit 1 (day 0) when serum and whole blood samples were taken.
|
FTY720
n=66 Participants
Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od.
|
Visit 3
Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od at visit 3
|
Visit 3
Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od at visit 3
|
|---|---|---|---|---|
|
Baseline Flow Cytometry Analyses for Blood Cytokines and Chemokines in Healthy Controls and RRMS Patients
CD3 abs
|
2048.14 absolute cell count
Standard Error 263.209
|
1610.94 absolute cell count
Standard Error 126.071
|
—
|
—
|
|
Baseline Flow Cytometry Analyses for Blood Cytokines and Chemokines in Healthy Controls and RRMS Patients
CD19 abs
|
311.63 absolute cell count
Standard Error 57.592
|
327.63 absolute cell count
Standard Error 44.421
|
—
|
—
|
|
Baseline Flow Cytometry Analyses for Blood Cytokines and Chemokines in Healthy Controls and RRMS Patients
NK abs
|
281.33 absolute cell count
Standard Error 39.106
|
623.57 absolute cell count
Standard Error 394.837
|
—
|
—
|
|
Baseline Flow Cytometry Analyses for Blood Cytokines and Chemokines in Healthy Controls and RRMS Patients
NKT abs
|
135.86 absolute cell count
Standard Error 16.627
|
104.36 absolute cell count
Standard Error 15.080
|
—
|
—
|
|
Baseline Flow Cytometry Analyses for Blood Cytokines and Chemokines in Healthy Controls and RRMS Patients
Hi CD16CD56 abs
|
26.64 absolute cell count
Standard Error 4.399
|
20.44 absolute cell count
Standard Error 3.506
|
—
|
—
|
|
Baseline Flow Cytometry Analyses for Blood Cytokines and Chemokines in Healthy Controls and RRMS Patients
CD4CD25 (CD3 gate)
|
26.08 absolute cell count
Standard Error 3.159
|
27.08 absolute cell count
Standard Error 1.251
|
—
|
—
|
|
Baseline Flow Cytometry Analyses for Blood Cytokines and Chemokines in Healthy Controls and RRMS Patients
Hi CD4CD25 (CD3 gate)
|
2.83 absolute cell count
Standard Error 0.383
|
3.33 absolute cell count
Standard Error 0.253
|
—
|
—
|
PRIMARY outcome
Timeframe: BaselinePopulation: Analysis was done in the healthy volunteers and RRMS patients.
Baseline peripheral blood flow cytometric analyses in study participants evaluated by flow cytometry analysis.
Outcome measures
| Measure |
Healthy Controls
n=60 Participants
Healthy volunteers had only Visit 1 (day 0) when serum and whole blood samples were taken.
|
FTY720
n=66 Participants
Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od.
|
Visit 3
Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od at visit 3
|
Visit 3
Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od at visit 3
|
|---|---|---|---|---|
|
Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline
IL9+ (in CD4+CD25+)
|
5.06 Percent of cells
Standard Error 4.497
|
0.59 Percent of cells
Standard Error 0.221
|
—
|
—
|
|
Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline
CD8+IL4+ % (in CD8+)
|
5.64 Percent of cells
Standard Error 3.74
|
1.87 Percent of cells
Standard Error 0.538
|
—
|
—
|
|
Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline
IL10+ (in CD4+CD25+)
|
2.57 Percent of cells
Standard Error 0.228
|
1.81 Percent of cells
Standard Error 0.464
|
—
|
—
|
|
Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline
IL4+ (in CD4+CD25+)
|
1.88 Percent of cells
Standard Error 0.34
|
0.50 Percent of cells
Standard Error 0.105
|
—
|
—
|
|
Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline
CD4+TNFa+ (in CD4+)
|
46.86 Percent of cells
Standard Error 4.892
|
23.72 Percent of cells
Standard Error 4.707
|
—
|
—
|
|
Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline
CD4+IL9+ (in CD4+)
|
0.22 Percent of cells
Standard Error 0.109
|
0.54 Percent of cells
Standard Error 0.163
|
—
|
—
|
|
Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline
CD8+TNFa+ (in CD8+)
|
35 Percent of cells
Standard Error 4.876
|
11.78 Percent of cells
Standard Error 2.679
|
—
|
—
|
|
Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline
CD8+IL9+ (in CD8+)
|
0.14 Percent of cells
Standard Error 0.087
|
0.90 Percent of cells
Standard Error 0.245
|
—
|
—
|
|
Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline
TNFa+ (in CD4+CD25+)
|
52.82 Percent of cells
Standard Error 5.019
|
23.29 Percent of cells
Standard Error 4.430
|
—
|
—
|
|
Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline
CD3 %
|
76.52 Percent of cells
Standard Error 1.494
|
71.92 Percent of cells
Standard Error 1.134
|
—
|
—
|
|
Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline
CD19 %
|
11.57 Percent of cells
Standard Error 1.018
|
13.72 Percent of cells
Standard Error 1.336
|
—
|
—
|
|
Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline
NK %
|
11.04 Percent of cells
Standard Error 1.328
|
10.17 Percent of cells
Standard Error 1.169
|
—
|
—
|
|
Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline
NKT %
|
5.65 Percent of cells
Standard Error 0.855
|
5.19 Percent of cells
Standard Error 0.766
|
—
|
—
|
|
Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline
Hi CD16CD56 %
|
1.05 Percent of cells
Standard Error 0.183
|
0.93 Percent of cells
Standard Error 0.145
|
—
|
—
|
|
Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline
CD3CD4 % (Lymphogate)
|
41.19 Percent of cells
Standard Error 2.483
|
44.91 Percent of cells
Standard Error 1.321
|
—
|
—
|
|
Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline
CD3CD8 % (Lymphogate)
|
23.23 Percent of cells
Standard Error 2.175
|
22.91 Percent of cells
Standard Error 1.188
|
—
|
—
|
|
Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline
CD3CD4 % (CD3 gate)
|
57.38 Percent of cells
Standard Error 2.722
|
62.99 Percent of cells
Standard Error 1.446
|
—
|
—
|
|
Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline
CD3CD8 % (CD3 gate)
|
35.11 Percent of cells
Standard Error 2.305
|
31.20 Percent of cells
Standard Error 1.351
|
—
|
—
|
|
Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline
CD4+IFNg+ (in CD4+)
|
7.42 Percent of cells
Standard Error 1.994
|
3.61 Percent of cells
Standard Error 1.037
|
—
|
—
|
|
Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline
CD4+IL17+ (in CD4+)
|
1.23 Percent of cells
Standard Error 0.173
|
1.27 Percent of cells
Standard Error 0.298
|
—
|
—
|
|
Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline
CD8+IFNg+ (in CD8+)
|
16.45 Percent of cells
Standard Error 3.896
|
5.47 Percent of cells
Standard Error 2.463
|
—
|
—
|
|
Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline
CD8+IL17+ (in CD8+)
|
1.71 Percent of cells
Standard Error 0.636
|
4.20 Percent of cells
Standard Error 0.923
|
—
|
—
|
|
Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline
IFNg+ (in CD4+CD25+)
|
7.1 Percent of cells
Standard Error 1.896
|
1.98 Percent of cells
Standard Error 0.469
|
—
|
—
|
|
Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline
IL17+ (in CD4+CD25+)
|
2.35 Percent of cells
Standard Error 0.264
|
2.06 Percent of cells
Standard Error 0.410
|
—
|
—
|
|
Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline
CD4+IL10+ (in CD4+)
|
1.64 Percent of cells
Standard Error 0.33
|
0.72 Percent of cells
Standard Error 0.196
|
—
|
—
|
|
Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline
CD4+IL4+ (in CD4+)
|
1.44 Percent of cells
Standard Error 0.294
|
0.96 Percent of cells
Standard Error 0.410
|
—
|
—
|
|
Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline
CD4-CD8-IL4+ (in CD4-CD8-)
|
1.31 Percent of cells
Standard Error 0.31
|
2.62 Percent of cells
Standard Error 1.125
|
—
|
—
|
|
Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline
CD8+IL10+ (in CD8+)
|
0.52 Percent of cells
Standard Error 0.089
|
0.31 Percent of cells
Standard Error 0.096
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, month 3, month 6Population: Intent to treat
Change of serum cytokine and chemokine levels measured by ELISA in RRMS patients treated with fingolimod between visits
Outcome measures
| Measure |
Healthy Controls
n=66 Participants
Healthy volunteers had only Visit 1 (day 0) when serum and whole blood samples were taken.
|
FTY720
n=66 Participants
Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od.
|
Visit 3
n=66 Participants
Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od at visit 3
|
Visit 3
Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od at visit 3
|
|---|---|---|---|---|
|
Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits
CXCL13=BLC
|
139.68 pg/ml
Standard Error 46.631
|
105.42 pg/ml
Standard Error 20.61
|
105.86 pg/ml
Standard Error 22.053
|
—
|
|
Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits
IL6
|
66.53 pg/ml
Standard Error 65.411
|
49.98 pg/ml
Standard Error 49.263
|
149.62 pg/ml
Standard Error 144.622
|
—
|
|
Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits
IL8
|
3.57 pg/ml
Standard Error 0.553
|
3.84 pg/ml
Standard Error 0.482
|
4.29 pg/ml
Standard Error 0.541
|
—
|
|
Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits
IL13
|
0.3 pg/ml
Standard Error 0.15
|
0.35 pg/ml
Standard Error 0.208
|
0.48 pg/ml
Standard Error 0.289
|
—
|
|
Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits
CCL5= RANTES
|
404.31 pg/ml
Standard Error 55.189
|
384.12 pg/ml
Standard Error 52.649
|
480.34 pg/ml
Standard Error 63.874
|
—
|
|
Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits
IL23
|
3.04 pg/ml
Standard Error 0.924
|
2.01 pg/ml
Standard Error 0.629
|
2.15 pg/ml
Standard Error 0.699
|
—
|
|
Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits
VLA4
|
0.58 pg/ml
Standard Error 0.201
|
0.76 pg/ml
Standard Error 0.356
|
0.82 pg/ml
Standard Error 0.36
|
—
|
|
Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits
CXCL10=IP-10 (CXCR3 ligand)
|
18.18 pg/ml
Standard Error 2.405
|
18.46 pg/ml
Standard Error 2.356
|
20.54 pg/ml
Standard Error 3.008
|
—
|
|
Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits
CCL2=MCP-1
|
62.89 pg/ml
Standard Error 8.42
|
74.38 pg/ml
Standard Error 10.011
|
92.73 pg/ml
Standard Error 13.626
|
—
|
|
Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits
IL4
|
2.36 pg/ml
Standard Error 0.149
|
1.94 pg/ml
Standard Error 0.099
|
2.12 pg/ml
Standard Error 0.145
|
—
|
|
Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits
IL17A
|
1.06 pg/ml
Standard Error 0.029
|
1.09 pg/ml
Standard Error 0.04
|
1.04 pg/ml
Standard Error 0.033
|
—
|
|
Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits
TNF
|
1.06 pg/ml
Standard Error 0.1
|
1.26 pg/ml
Standard Error 0.196
|
1.12 pg/ml
Standard Error 0.139
|
—
|
|
Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits
IL22
|
22.41 pg/ml
Standard Error 0.69
|
22.45 pg/ml
Standard Error 0.843
|
22.99 pg/ml
Standard Error 0.739
|
—
|
SECONDARY outcome
Timeframe: Baseline, Month 3, Month 6Population: Intent to treat. Data analyzed in RRMS patients.
Peripheral blood chemokine cytokine levels measured by flow cytometry during fingolimod treatment in healthy controls at baseline and in RRMS patients between visits
Outcome measures
| Measure |
Healthy Controls
n=60 Participants
Healthy volunteers had only Visit 1 (day 0) when serum and whole blood samples were taken.
|
FTY720
n=66 Participants
Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od.
|
Visit 3
n=66 Participants
Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od at visit 3
|
Visit 3
n=66 Participants
Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od at visit 3
|
|---|---|---|---|---|
|
Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
CD3 abs
|
2048.14 pg/ml
Standard Error 263.209
|
1610.94 pg/ml
Standard Error 126.071
|
339.74 pg/ml
Standard Error 43.44
|
314.75 pg/ml
Standard Error 30.15
|
|
Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
CD19 abs
|
311.63 pg/ml
Standard Error 57.592
|
327.63 pg/ml
Standard Error 44.421
|
32.9 pg/ml
Standard Error 5.347
|
26.56 pg/ml
Standard Error 2.879
|
|
Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
NK abs
|
281.33 pg/ml
Standard Error 39.106
|
623.57 pg/ml
Standard Error 394.837
|
203.66 pg/ml
Standard Error 30.487
|
181.97 pg/ml
Standard Error 20.715
|
|
Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
NKT abs
|
135.86 pg/ml
Standard Error 16.627
|
104.36 pg/ml
Standard Error 15.08
|
88.45 pg/ml
Standard Error 12.725
|
88.98 pg/ml
Standard Error 11.046
|
|
Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
Hi CD16CD56 abs
|
26.64 pg/ml
Standard Error 4.399
|
20.44 pg/ml
Standard Error 3.506
|
29.35 pg/ml
Standard Error 8.73
|
30.04 pg/ml
Standard Error 6.59
|
|
Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
CD4CD25 (CD3 gate)
|
26.08 pg/ml
Standard Error 3.159
|
27.03 pg/ml
Standard Error 1.251
|
9.24 pg/ml
Standard Error 1.407
|
9.22 pg/ml
Standard Error 1.399
|
|
Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
Hi CD4CD25 (CD3 gate)
|
2.83 pg/ml
Standard Error 0.383
|
3.33 pg/ml
Standard Error 0.253
|
2.03 pg/ml
Standard Error 0.302
|
1.77 pg/ml
Standard Error 0.267
|
SECONDARY outcome
Timeframe: Baseline, Month 3, Month 6Population: Intent to treat. Data analyzed in RRMS patients.
Peripheral blood chemokine cytokine levels measured by flow cytometry at baseline and between visits during fingolimod treatment. Absolute counts of the cells were calculated according to the absolute lymphocyte counts and the percentages of cells. This allowed for a clear determination of cell counts and thus increased the reliability of the results.
Outcome measures
| Measure |
Healthy Controls
n=60 Participants
Healthy volunteers had only Visit 1 (day 0) when serum and whole blood samples were taken.
|
FTY720
n=66 Participants
Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od.
|
Visit 3
n=66 Participants
Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od at visit 3
|
Visit 3
n=66 Participants
Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od at visit 3
|
|---|---|---|---|---|
|
Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
CD3CD4 (Lymphogate)
|
41.19 absolute cell count
Standard Error 2.483
|
44.91 absolute cell count
Standard Error 1.321
|
13.64 absolute cell count
Standard Error 1.712
|
13.9 absolute cell count
Standard Error 1.522
|
|
Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
CD3CD8 (Lymphogate)
|
23.23 absolute cell count
Standard Error 2.175
|
22.91 absolute cell count
Standard Error 1.188
|
32.93 absolute cell count
Standard Error 1.967
|
32.22 absolute cell count
Standard Error 2.169
|
|
Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
CD3CD4 (CD3 gate)
|
57.38 absolute cell count
Standard Error 2.722
|
62.99 absolute cell count
Standard Error 1.446
|
23.26 absolute cell count
Standard Error 2.726
|
24 absolute cell count
Standard Error 2.788
|
|
Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
CD3CD8 (CD3 gate)
|
35.11 absolute cell count
Standard Error 2.305
|
31.2 absolute cell count
Standard Error 1.351
|
59.52 absolute cell count
Standard Error 2.534
|
59.66 absolute cell count
Standard Error 2.642
|
|
Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
CD8+IL9+ (in CD8+)
|
0.14 absolute cell count
Standard Error 0.087
|
0.9 absolute cell count
Standard Error 0.245
|
0.13 absolute cell count
Standard Error 0.061
|
0.14 absolute cell count
Standard Error 0.068
|
|
Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
TNFa+ (in CD4+CD25+)
|
52.82 absolute cell count
Standard Error 0.019
|
23.29 absolute cell count
Standard Error 4.43
|
30.39 absolute cell count
Standard Error 5.391
|
40.4 absolute cell count
Standard Error 4.907
|
|
Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
IL9+ (in CD4+CD25+)
|
5.06 absolute cell count
Standard Error 4.497
|
0.59 absolute cell count
Standard Error 0.221
|
0.72 absolute cell count
Standard Error 0.213
|
1.3 absolute cell count
Standard Error 0.507
|
|
Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
CD4+IFNg+ (in CD4+)
|
7.42 absolute cell count
Standard Error 1.994
|
3.61 absolute cell count
Standard Error 1.037
|
7.85 absolute cell count
Standard Error 2.197
|
13.97 absolute cell count
Standard Error 2.972
|
|
Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
CD4+IL17+ (in CD4+)
|
1.23 absolute cell count
Standard Error 0.173
|
1.27 absolute cell count
Standard Error 0.298
|
1.26 absolute cell count
Standard Error 0.224
|
2.02 absolute cell count
Standard Error 0.342
|
|
Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
CD8+IFNg+ (in CD8+)
|
16.45 absolute cell count
Standard Error 3.896
|
5.47 absolute cell count
Standard Error 2.463
|
5.73 absolute cell count
Standard Error 1.968
|
14.7 absolute cell count
Standard Error 3.834
|
|
Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
CD8+IL17+ (in CD8+)
|
1.71 absolute cell count
Standard Error 0.636
|
4.2 absolute cell count
Standard Error 0.923
|
9.22 absolute cell count
Standard Error 3.105
|
2.23 absolute cell count
Standard Error 0.505
|
|
Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
IFNg+ (in CD4+CD25+)
|
7.1 absolute cell count
Standard Error 1.896
|
1.98 absolute cell count
Standard Error 0.469
|
7.07 absolute cell count
Standard Error 1.719
|
9.31 absolute cell count
Standard Error 1.699
|
|
Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
IL17+ (in CD4+CD25+)
|
2.35 absolute cell count
Standard Error 0.264
|
2.06 absolute cell count
Standard Error 0.41
|
1.85 absolute cell count
Standard Error 0.31
|
2.7 absolute cell count
Standard Error 0.451
|
|
Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
CD4+IL10+ (in CD4+)
|
1.64 absolute cell count
Standard Error 0.33
|
0.72 absolute cell count
Standard Error 0.196
|
1.51 absolute cell count
Standard Error 0.422
|
2.14 absolute cell count
Standard Error 0.486
|
|
Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
CD4+IL4+ (in CD4+)
|
1.44 absolute cell count
Standard Error 2.94
|
0.96 absolute cell count
Standard Error 0.41
|
1.45 absolute cell count
Standard Error 0.294
|
2.32 absolute cell count
Standard Error 0.43
|
|
Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
CD4-CD8-IL4+ (in CD4-CD8-)
|
1.31 absolute cell count
Standard Error 0.31
|
2.62 absolute cell count
Standard Error 1.125
|
1.77 absolute cell count
Standard Error 0.267
|
2.64 absolute cell count
Standard Error 0.909
|
|
Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
CD8+IL10+ (in CD8+)
|
0.52 absolute cell count
Standard Error 0.089
|
0.31 absolute cell count
Standard Error 0.096
|
0.25 absolute cell count
Standard Error 0.107
|
0.67 absolute cell count
Standard Error 0.169
|
|
Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
IL10+ (in CD4+CD25+)
|
2.57 absolute cell count
Standard Error 0.228
|
1.81 absolute cell count
Standard Error 0.464
|
2.88 absolute cell count
Standard Error 0.471
|
4.03 absolute cell count
Standard Error 0.793
|
|
Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
IL4+ (in CD4+CD25+)
|
1.88 absolute cell count
Standard Error 0.34
|
0.5 absolute cell count
Standard Error 0.105
|
1.22 absolute cell count
Standard Error 0.224
|
1.49 absolute cell count
Standard Error 0.316
|
|
Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
CD4+TNFa+ (in CD4+)
|
46.86 absolute cell count
Standard Error 4.892
|
23.72 absolute cell count
Standard Error 4.707
|
29.45 absolute cell count
Standard Error 5.681
|
49.96 absolute cell count
Standard Error 5.832
|
|
Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
CD4+IL9+ (in CD4+)
|
0.22 absolute cell count
Standard Error 0.109
|
0.54 absolute cell count
Standard Error 0.163
|
0.4 absolute cell count
Standard Error 0.098
|
0.47 absolute cell count
Standard Error 0.143
|
|
Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
CD8+TNFa+ (in CD8+)
|
35 absolute cell count
Standard Error 4.876
|
11.78 absolute cell count
Standard Error 2.679
|
20.93 absolute cell count
Standard Error 5.361
|
41.53 absolute cell count
Standard Error 6.18
|
SECONDARY outcome
Timeframe: Baseline, Month 3, Month 6Population: Intent to treat. Data analyzed in RRMS patients.
Peripheral blood chemokine cytokine levels measured by flow cytometry in healthy controls at baseline and in RRMS patients between visits during fingolimod treatment
Outcome measures
| Measure |
Healthy Controls
n=60 Participants
Healthy volunteers had only Visit 1 (day 0) when serum and whole blood samples were taken.
|
FTY720
n=66 Participants
Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od.
|
Visit 3
n=66 Participants
Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od at visit 3
|
Visit 3
n=66 Participants
Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od at visit 3
|
|---|---|---|---|---|
|
Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
CD3 %
|
76.52 percent of cell count
Standard Error 1.494
|
71.92 percent of cell count
Standard Error 1.134
|
57.61 percent of cell count
Standard Error 2.401
|
59.29 percent of cell count
Standard Error 2.318
|
|
Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
CD19 %
|
11.57 percent of cell count
Standard Error 0.018
|
13.72 percent of cell count
Standard Error 1.336
|
6.13 percent of cell count
Standard Error 0.847
|
5.14 percent of cell count
Standard Error 0.427
|
|
Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
NK %
|
0.427 percent of cell count
Standard Error 1.328
|
10.17 percent of cell count
Standard Error 1.169
|
34.48 percent of cell count
Standard Error 2.758
|
33.91 percent of cell count
Standard Error 2.238
|
|
Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
NKT %
|
5.65 percent of cell count
Standard Error 0.855
|
5.19 percent of cell count
Standard Error 0.766
|
15.55 percent of cell count
Standard Error 1.726
|
17.66 percent of cell count
Standard Error 1.985
|
|
Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
Hi CD16CD56 %
|
1.05 percent of cell count
Standard Error 0.183
|
0.93 percent of cell count
Standard Error 0.145
|
5.29 percent of cell count
Standard Error 1.296
|
6.20 percent of cell count
Standard Error 1.423
|
|
Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients
CD8+IL4+ % (in CD8+)
|
5.64 percent of cell count
Standard Error 3.74
|
1.87 percent of cell count
Standard Error 0.538
|
3.13 percent of cell count
Standard Error 0.964
|
1.91 percent of cell count
Standard Error 1.225
|
Adverse Events
Fingolimod 0.5 mg
Serious events: 3 serious events
Other events: 7 other events
Deaths: 0 deaths
All Patients
Serious events: 3 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Fingolimod 0.5 mg
n=66 participants at risk
Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od.
|
All Patients
n=66 participants at risk
All patients in the trial
|
|---|---|---|
|
Cardiac disorders
Sinus bradycardia
|
3.0%
2/66 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Visit until 30 days after Last Patient Last Visit) up to approximately 2 years.
Only patients who received at least one dose of the investigational drug (N=66) were included in the data set used for safety.
|
3.0%
2/66 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Visit until 30 days after Last Patient Last Visit) up to approximately 2 years.
Only patients who received at least one dose of the investigational drug (N=66) were included in the data set used for safety.
|
|
Infections and infestations
Herpes zoster
|
1.5%
1/66 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Visit until 30 days after Last Patient Last Visit) up to approximately 2 years.
Only patients who received at least one dose of the investigational drug (N=66) were included in the data set used for safety.
|
1.5%
1/66 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Visit until 30 days after Last Patient Last Visit) up to approximately 2 years.
Only patients who received at least one dose of the investigational drug (N=66) were included in the data set used for safety.
|
Other adverse events
| Measure |
Fingolimod 0.5 mg
n=66 participants at risk
Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od.
|
All Patients
n=66 participants at risk
All patients in the trial
|
|---|---|---|
|
Infections and infestations
Influenza
|
3.0%
2/66 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Visit until 30 days after Last Patient Last Visit) up to approximately 2 years.
Only patients who received at least one dose of the investigational drug (N=66) were included in the data set used for safety.
|
3.0%
2/66 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Visit until 30 days after Last Patient Last Visit) up to approximately 2 years.
Only patients who received at least one dose of the investigational drug (N=66) were included in the data set used for safety.
|
|
Investigations
Gamma-glutamyltransferase increased
|
1.5%
1/66 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Visit until 30 days after Last Patient Last Visit) up to approximately 2 years.
Only patients who received at least one dose of the investigational drug (N=66) were included in the data set used for safety.
|
1.5%
1/66 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Visit until 30 days after Last Patient Last Visit) up to approximately 2 years.
Only patients who received at least one dose of the investigational drug (N=66) were included in the data set used for safety.
|
|
Investigations
Lymphocyte count decreased
|
1.5%
1/66 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Visit until 30 days after Last Patient Last Visit) up to approximately 2 years.
Only patients who received at least one dose of the investigational drug (N=66) were included in the data set used for safety.
|
1.5%
1/66 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Visit until 30 days after Last Patient Last Visit) up to approximately 2 years.
Only patients who received at least one dose of the investigational drug (N=66) were included in the data set used for safety.
|
|
Investigations
White blood cell count decreased
|
1.5%
1/66 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Visit until 30 days after Last Patient Last Visit) up to approximately 2 years.
Only patients who received at least one dose of the investigational drug (N=66) were included in the data set used for safety.
|
1.5%
1/66 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Visit until 30 days after Last Patient Last Visit) up to approximately 2 years.
Only patients who received at least one dose of the investigational drug (N=66) were included in the data set used for safety.
|
|
Nervous system disorders
Headache
|
1.5%
1/66 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Visit until 30 days after Last Patient Last Visit) up to approximately 2 years.
Only patients who received at least one dose of the investigational drug (N=66) were included in the data set used for safety.
|
1.5%
1/66 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Visit until 30 days after Last Patient Last Visit) up to approximately 2 years.
Only patients who received at least one dose of the investigational drug (N=66) were included in the data set used for safety.
|
|
Nervous system disorders
Muscle contractions involuntary
|
1.5%
1/66 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Visit until 30 days after Last Patient Last Visit) up to approximately 2 years.
Only patients who received at least one dose of the investigational drug (N=66) were included in the data set used for safety.
|
1.5%
1/66 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Visit until 30 days after Last Patient Last Visit) up to approximately 2 years.
Only patients who received at least one dose of the investigational drug (N=66) were included in the data set used for safety.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER