Fingolimod Effect on Cytokine and Chemokine Levels
Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT02373098
Collaborator
(none)
126
3
2
21.7
42
1.9
Study Details
Study Description
Brief Summary
The main purpose of this study was to measure the serum levels of cytokines and chemokines that are known to increase during multiple sclerosis relapses.
Cytokines are a broad and loose category of small proteins that are important in cell signaling.
The second purpose of the study was to test the cytokine/chemokine changes measured in the 3rd and 6th months on the efficacy parameters.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
126 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Intervention Model Description:
A 6-month, multicenter, prospective, interventional, single arm, open label study investigating the effects of fingolimod administered according to local label recommendations on Cytokine and Chemokine Levels in Relapsing Remitting Multiple Sclerosis PatientsA 6-month, multicenter, prospective, interventional, single arm, open label study investigating the effects of fingolimod administered according to local label recommendations on Cytokine and Chemokine Levels in Relapsing Remitting Multiple Sclerosis Patients
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Effects of Fingolimod (Gilenya®) on Cytokine and Chemokine Levels in Relapsing Remitting Multiple Sclerosis Patients
Actual Study Start Date
:
Mar 31, 2015
Actual Primary Completion Date
:
Jan 18, 2017
Actual Study Completion Date
:
Jan 18, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: FTY720
|
Drug: Fingolimod 0.5 mg
66 relapsing remitting MS (RRMS) patients were recruited. Patients who met all inclusion and none of the exclusion criteria were treated by Fingolimod 0.5 mg.
|
| No Intervention: Healthy volunteers Healthy volunteers with no intervention or drug administered. |
Outcome Measures
Primary Outcome Measures
- Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA [Baseline]
Blood samples were taken at baseline and measurements were performed before treatment of fingolimod.
- Baseline Flow Cytometry Analyses for Blood Cytokines and Chemokines in Healthy Controls and RRMS Patients [Baseline]
baseline peripheral blood flow cytometric analysis in study participants
- Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline [Baseline]
Baseline peripheral blood flow cytometric analyses in study participants evaluated by flow cytometry analysis.
Secondary Outcome Measures
- Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits [Baseline, month 3, month 6]
Change of serum cytokine and chemokine levels measured by ELISA in RRMS patients treated with fingolimod between visits
- Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients [Baseline, Month 3, Month 6]
Peripheral blood chemokine cytokine levels measured by flow cytometry during fingolimod treatment in healthy controls at baseline and in RRMS patients between visits
- Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients [Baseline, Month 3, Month 6]
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.
- Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients [Baseline, Month 3, Month 6]
Peripheral blood chemokine cytokine levels measured by flow cytometry in healthy controls at baseline and in RRMS patients between visits during fingolimod treatment
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Key Inclusion Criteria:
-
Written informed consent must be obtained before the beginning of te study
-
Nonresponder RRMS patients
-
Last relapse of the patient should be at least 2 months before study entry.
-
Last interferon or glatiramer acetate dose of the patient should be at least 1 month before study entry.
Key Exclusion Criteria:
-
Patients with secondary progressive MS.
-
Patients with known contraindications for fingolimod treatment.
-
Other coexistent autoimmune diseases
-
Pregnant or nursing (lactating) women
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Mecidiyekoy | Istanbul | Turkey | 34394 |
| 2 | Novartis Investigative Site | Uskudar | Istanbul | Turkey | 34668 |
| 3 | Novartis Investigative Site | Istanbul | Turkey | 34093 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02373098
Other Study ID Numbers:
- CFTY720DTR04
First Posted:
Feb 26, 2015
Last Update Posted:
Sep 30, 2019
Last Verified:
Sep 1, 2019
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | FTY720 | Healthy Volunteers |
|---|---|---|
| Arm/Group Description | Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od. | The healthy volunteers had only Visit 1 (Day 0) and served as control group for cytokine/chemokine measurements |
| Period Title: Overall Study | ||
| STARTED | 66 | 60 |
| COMPLETED | 54 | 60 |
| NOT COMPLETED | 12 | 0 |
Baseline Characteristics
| Arm/Group Title | FTY720 | Healthy Volunteers | Total |
|---|---|---|---|
| Arm/Group Description | Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od. | The healthy volunteers had only Visit 1 (Day 0) and served as control group for cytokine/chemokine measurements | Total of all reporting groups |
| Overall Participants | 66 | 60 | 126 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
35.75
(8.20)
|
34.73
(9.62)
|
35.27
(8.89)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
46
69.7%
|
40
66.7%
|
86
68.3%
|
| Male |
20
30.3%
|
20
33.3%
|
40
31.7%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| Turkish |
66
100%
|
60
100%
|
126
100%
|
Outcome Measures
| Title | Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA |
|---|---|
| Description | Blood samples were taken at baseline and measurements were performed before treatment of fingolimod. |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat |
| Arm/Group Title | Healthy Controls | FTY720 |
|---|---|---|
| Arm/Group Description | Healthy volunteers had only Visit 1 (day 0) when serum and whole blood samples were taken. | Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od. |
| Measure Participants | 60 | 66 |
| CCL5 (RANTES) |
212.26
(22.48)
|
404.31
(55.189)
|
| IL-17A |
1.15
(0.03)
|
1.06
(0.029)
|
| CXCL13 |
110.8
(22.3)
|
139.68
(46.631)
|
| IL6 |
0.88
(0.324)
|
66.53
(65.411)
|
| IL8 |
3.25
(0.47)
|
3.57
(0.553)
|
| IL13 |
0.49
(0.331)
|
0.3
(0.15)
|
| IL23 |
1.29
(0.552)
|
3.04
(0.924)
|
| VLA4 |
1.17
(0.396)
|
0.58
(0.201)
|
| CXCL10=IP-10 (CXCR3 ligand) |
16.09
(1.76)
|
18.18
(2.405)
|
| CCL2=MCP-1 |
52.88
(4.281)
|
62.89
(8.42)
|
| IL4 |
2.02
(0.077)
|
2.36
(0.149)
|
| TNF alpha |
1.1
(0.195)
|
1.06
(0.1)
|
| IL22 |
22.36
(0.581)
|
22.41
(0.547)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | CCL5=RANTES | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.000 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | IL17A | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.035 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | CXCL13 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.911 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | IL6 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.000 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | IL8 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.934 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | IL13 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.727 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | IL23 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.179 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | VLA4 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.208 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | CXCL10=IP-10 (CXCR3 ligand) | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.730 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | CCL2=MCP-1 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.725 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | IL4 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.057 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | TNF alpha | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.724 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | IL22 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.662 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Baseline Flow Cytometry Analyses for Blood Cytokines and Chemokines in Healthy Controls and RRMS Patients |
|---|---|
| Description | baseline peripheral blood flow cytometric analysis in study participants |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done in the healthy volunteers and RRMS patients. |
| Arm/Group Title | Healthy Controls | FTY720 |
|---|---|---|
| Arm/Group Description | Healthy volunteers had only Visit 1 (day 0) when serum and whole blood samples were taken. | Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od. |
| Measure Participants | 60 | 66 |
| CD3 abs |
2048.14
(263.209)
|
1610.94
(126.071)
|
| CD19 abs |
311.63
(57.592)
|
327.63
(44.421)
|
| NK abs |
281.33
(39.106)
|
623.57
(394.837)
|
| NKT abs |
135.86
(16.627)
|
104.36
(15.080)
|
| Hi CD16CD56 abs |
26.64
(4.399)
|
20.44
(3.506)
|
| CD4CD25 (CD3 gate) |
26.08
(3.159)
|
27.08
(1.251)
|
| Hi CD4CD25 (CD3 gate) |
2.83
(0.383)
|
3.33
(0.253)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | CD3 abs | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.256 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | CD19 abs | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.587 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | NK abs | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.300 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | NKT abs | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.096 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | Hi CD16CD56 abs | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.270 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | CD4CD25 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.902 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | Hi CD4CD25 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.283 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits |
|---|---|
| Description | Change of serum cytokine and chemokine levels measured by ELISA in RRMS patients treated with fingolimod between visits |
| Time Frame | Baseline, month 3, month 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat |
| Arm/Group Title | Visit 1 | Visit 2 | Visit 3 |
|---|---|---|---|
| Arm/Group Description | Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od at visit 1 | Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od at visit 2 | Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od at visit 3 |
| Measure Participants | 66 | 66 | 66 |
| CXCL13=BLC |
139.68
(46.631)
|
105.42
(20.61)
|
105.86
(22.053)
|
| IL6 |
66.53
(65.411)
|
49.98
(49.263)
|
149.62
(144.622)
|
| IL8 |
3.57
(0.553)
|
3.84
(0.482)
|
4.29
(0.541)
|
| IL13 |
0.3
(0.15)
|
0.35
(0.208)
|
0.48
(0.289)
|
| CCL5= RANTES |
404.31
(55.189)
|
384.12
(52.649)
|
480.34
(63.874)
|
| IL23 |
3.04
(0.924)
|
2.01
(0.629)
|
2.15
(0.699)
|
| VLA4 |
0.58
(0.201)
|
0.76
(0.356)
|
0.82
(0.36)
|
| CXCL10=IP-10 (CXCR3 ligand) |
18.18
(2.405)
|
18.46
(2.356)
|
20.54
(3.008)
|
| CCL2=MCP-1 |
62.89
(8.42)
|
74.38
(10.011)
|
92.73
(13.626)
|
| IL4 |
2.36
(0.149)
|
1.94
(0.099)
|
2.12
(0.145)
|
| IL17A |
1.06
(0.029)
|
1.09
(0.04)
|
1.04
(0.033)
|
| TNF |
1.06
(0.1)
|
1.26
(0.196)
|
1.12
(0.139)
|
| IL22 |
22.41
(0.69)
|
22.45
(0.843)
|
22.99
(0.739)
|
| Title | Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients |
|---|---|
| Description | Peripheral blood chemokine cytokine levels measured by flow cytometry during fingolimod treatment in healthy controls at baseline and in RRMS patients between visits |
| Time Frame | Baseline, Month 3, Month 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat. Data analyzed in RRMS patients. |
| Arm/Group Title | Healthy Controls | Visit 1 | Visit 2 | Visit 3 |
|---|---|---|---|---|
| Arm/Group Description | Healthy volunteers had only Visit 1 (day 0) when serum and whole blood samples were taken. | Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od at visit 1 | Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od at visit 2 | Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od at visit 3 |
| Measure Participants | 60 | 66 | 66 | 66 |
| CD3 abs |
2048.14
(263.209)
|
1610.94
(126.071)
|
339.74
(43.44)
|
314.75
(30.15)
|
| CD19 abs |
311.63
(57.592)
|
327.63
(44.421)
|
32.9
(5.347)
|
26.56
(2.879)
|
| NK abs |
281.33
(39.106)
|
623.57
(394.837)
|
203.66
(30.487)
|
181.97
(20.715)
|
| NKT abs |
135.86
(16.627)
|
104.36
(15.08)
|
88.45
(12.725)
|
88.98
(11.046)
|
| Hi CD16CD56 abs |
26.64
(4.399)
|
20.44
(3.506)
|
29.35
(8.73)
|
30.04
(6.59)
|
| CD4CD25 (CD3 gate) |
26.08
(3.159)
|
27.03
(1.251)
|
9.24
(1.407)
|
9.22
(1.399)
|
| Hi CD4CD25 (CD3 gate) |
2.83
(0.383)
|
3.33
(0.253)
|
2.03
(0.302)
|
1.77
(0.267)
|
| Title | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline |
|---|---|
| Description | Baseline peripheral blood flow cytometric analyses in study participants evaluated by flow cytometry analysis. |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done in the healthy volunteers and RRMS patients. |
| Arm/Group Title | Healthy Controls | FTY720 |
|---|---|---|
| Arm/Group Description | Healthy volunteers had only Visit 1 (day 0) when serum and whole blood samples were taken. | Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od. |
| Measure Participants | 60 | 66 |
| CD3 % |
76.52
(1.494)
|
71.92
(1.134)
|
| CD19 % |
11.57
(1.018)
|
13.72
(1.336)
|
| NK % |
11.04
(1.328)
|
10.17
(1.169)
|
| NKT % |
5.65
(0.855)
|
5.19
(0.766)
|
| Hi CD16CD56 % |
1.05
(0.183)
|
0.93
(0.145)
|
| CD3CD4 % (Lymphogate) |
41.19
(2.483)
|
44.91
(1.321)
|
| CD3CD8 % (Lymphogate) |
23.23
(2.175)
|
22.91
(1.188)
|
| CD3CD4 % (CD3 gate) |
57.38
(2.722)
|
62.99
(1.446)
|
| CD3CD8 % (CD3 gate) |
35.11
(2.305)
|
31.20
(1.351)
|
| CD4+IFNg+ (in CD4+) |
7.42
(1.994)
|
3.61
(1.037)
|
| CD4+IL17+ (in CD4+) |
1.23
(0.173)
|
1.27
(0.298)
|
| CD8+IFNg+ (in CD8+) |
16.45
(3.896)
|
5.47
(2.463)
|
| CD8+IL17+ (in CD8+) |
1.71
(0.636)
|
4.20
(0.923)
|
| IFNg+ (in CD4+CD25+) |
7.1
(1.896)
|
1.98
(0.469)
|
| IL17+ (in CD4+CD25+) |
2.35
(0.264)
|
2.06
(0.410)
|
| CD4+IL10+ (in CD4+) |
1.64
(0.33)
|
0.72
(0.196)
|
| CD4+IL4+ (in CD4+) |
1.44
(0.294)
|
0.96
(0.410)
|
| CD4-CD8-IL4+ (in CD4-CD8-) |
1.31
(0.31)
|
2.62
(1.125)
|
| CD8+IL10+ (in CD8+) |
0.52
(0.089)
|
0.31
(0.096)
|
| CD8+IL4+ % (in CD8+) |
5.64
(3.74)
|
1.87
(0.538)
|
| IL10+ (in CD4+CD25+) |
2.57
(0.228)
|
1.81
(0.464)
|
| IL4+ (in CD4+CD25+) |
1.88
(0.34)
|
0.50
(0.105)
|
| CD4+TNFa+ (in CD4+) |
46.86
(4.892)
|
23.72
(4.707)
|
| CD4+IL9+ (in CD4+) |
0.22
(0.109)
|
0.54
(0.163)
|
| CD8+TNFa+ (in CD8+) |
35
(4.876)
|
11.78
(2.679)
|
| CD8+IL9+ (in CD8+) |
0.14
(0.087)
|
0.90
(0.245)
|
| TNFa+ (in CD4+CD25+) |
52.82
(5.019)
|
23.29
(4.430)
|
| IL9+ (in CD4+CD25+) |
5.06
(4.497)
|
0.59
(0.221)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | CD3 % | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.017 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | CD19 % | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.300 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | NK % | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.657 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | NKT % | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.439 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | Hi CD16CD56 % | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.449 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | CD3CD4 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.356 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | CD3CD8 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.787 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | CD3CD4 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.121 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | CD3CD8 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.209 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | CD4+IFNg+ (in CD4+) | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.069 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | CD4+IL17+ (in CD4+) | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.402 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | CD8+IFNg+ (in CD8+) | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.017 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | CD8+IL17+ (in CD8+) | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.017 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | IFNg+ (in CD4+CD25+) | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.026 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | IL17+ (in CD4+CD25+) | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.168 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | CD4+IL10+ (in CD4+) | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.004 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | CD4+IL4+ (in CD4+) | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.013 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | CD4-CD8-IL4+ (in CD4-CD8-) | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.171 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | CD8+IL10+ (in CD8+) | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.013 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | CD8+IL4+ (in CD8+) | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.013 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | IL10+ (in CD4+CD25+) | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.007 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | IL4+ (in CD4+CD25+) | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.001 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | CD4+TNFa+ (in CD4+) | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 24
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | CD4+IL9+ (in CD4+) | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.107 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 25
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | CD8+TNFa+ (in CD8+) | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.000 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 26
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | CD8+IL9+ (in CD8+) | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.022 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 27
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | TNFa+ (in CD4+CD25+) | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.001 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 28
| Statistical Analysis Overview | Comparison Group Selection | Healthy Controls, FTY720 |
|---|---|---|
| Comments | IL9+ (in CD4+CD25+) | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.127 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Month 3, Month 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat. Data analyzed in RRMS patients. |
| Arm/Group Title | Healthy Controls | Visit 1 | Visit 2 | Visit 3 |
|---|---|---|---|---|
| Arm/Group Description | Healthy volunteers had only Visit 1 (day 0) when serum and whole blood samples were taken. | Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od at visit 1 | Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od at visit 2 | Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od at visit 3 |
| Measure Participants | 60 | 66 | 66 | 66 |
| CD3CD4 (Lymphogate) |
41.19
(2.483)
|
44.91
(1.321)
|
13.64
(1.712)
|
13.9
(1.522)
|
| CD3CD8 (Lymphogate) |
23.23
(2.175)
|
22.91
(1.188)
|
32.93
(1.967)
|
32.22
(2.169)
|
| CD3CD4 (CD3 gate) |
57.38
(2.722)
|
62.99
(1.446)
|
23.26
(2.726)
|
24
(2.788)
|
| CD3CD8 (CD3 gate) |
35.11
(2.305)
|
31.2
(1.351)
|
59.52
(2.534)
|
59.66
(2.642)
|
| CD4+IFNg+ (in CD4+) |
7.42
(1.994)
|
3.61
(1.037)
|
7.85
(2.197)
|
13.97
(2.972)
|
| CD4+IL17+ (in CD4+) |
1.23
(0.173)
|
1.27
(0.298)
|
1.26
(0.224)
|
2.02
(0.342)
|
| CD8+IFNg+ (in CD8+) |
16.45
(3.896)
|
5.47
(2.463)
|
5.73
(1.968)
|
14.7
(3.834)
|
| CD8+IL17+ (in CD8+) |
1.71
(0.636)
|
4.2
(0.923)
|
9.22
(3.105)
|
2.23
(0.505)
|
| IFNg+ (in CD4+CD25+) |
7.1
(1.896)
|
1.98
(0.469)
|
7.07
(1.719)
|
9.31
(1.699)
|
| IL17+ (in CD4+CD25+) |
2.35
(0.264)
|
2.06
(0.41)
|
1.85
(0.31)
|
2.7
(0.451)
|
| CD4+IL10+ (in CD4+) |
1.64
(0.33)
|
0.72
(0.196)
|
1.51
(0.422)
|
2.14
(0.486)
|
| CD4+IL4+ (in CD4+) |
1.44
(2.94)
|
0.96
(0.41)
|
1.45
(0.294)
|
2.32
(0.43)
|
| CD4-CD8-IL4+ (in CD4-CD8-) |
1.31
(0.31)
|
2.62
(1.125)
|
1.77
(0.267)
|
2.64
(0.909)
|
| CD8+IL10+ (in CD8+) |
0.52
(0.089)
|
0.31
(0.096)
|
0.25
(0.107)
|
0.67
(0.169)
|
| IL10+ (in CD4+CD25+) |
2.57
(0.228)
|
1.81
(0.464)
|
2.88
(0.471)
|
4.03
(0.793)
|
| IL4+ (in CD4+CD25+) |
1.88
(0.34)
|
0.5
(0.105)
|
1.22
(0.224)
|
1.49
(0.316)
|
| CD4+TNFa+ (in CD4+) |
46.86
(4.892)
|
23.72
(4.707)
|
29.45
(5.681)
|
49.96
(5.832)
|
| CD4+IL9+ (in CD4+) |
0.22
(0.109)
|
0.54
(0.163)
|
0.4
(0.098)
|
0.47
(0.143)
|
| CD8+TNFa+ (in CD8+) |
35
(4.876)
|
11.78
(2.679)
|
20.93
(5.361)
|
41.53
(6.18)
|
| CD8+IL9+ (in CD8+) |
0.14
(0.087)
|
0.9
(0.245)
|
0.13
(0.061)
|
0.14
(0.068)
|
| TNFa+ (in CD4+CD25+) |
52.82
(0.019)
|
23.29
(4.43)
|
30.39
(5.391)
|
40.4
(4.907)
|
| IL9+ (in CD4+CD25+) |
5.06
(4.497)
|
0.59
(0.221)
|
0.72
(0.213)
|
1.3
(0.507)
|
| Title | Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients |
|---|---|
| Description | Peripheral blood chemokine cytokine levels measured by flow cytometry in healthy controls at baseline and in RRMS patients between visits during fingolimod treatment |
| Time Frame | Baseline, Month 3, Month 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat. Data analyzed in RRMS patients. |
| Arm/Group Title | Healthy Controls | Visit 1 | Visit 2 | Visit 3 |
|---|---|---|---|---|
| Arm/Group Description | Healthy volunteers had only Visit 1 (day 0) when serum and whole blood samples were taken. | Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od at visit 1 | Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od at visit 2 | Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od at visit 3 |
| Measure Participants | 60 | 66 | 66 | 66 |
| CD3 % |
76.52
(1.494)
|
71.92
(1.134)
|
57.61
(2.401)
|
59.29
(2.318)
|
| CD19 % |
11.57
(0.018)
|
13.72
(1.336)
|
6.13
(0.847)
|
5.14
(0.427)
|
| NK % |
0.427
(1.328)
|
10.17
(1.169)
|
34.48
(2.758)
|
33.91
(2.238)
|
| NKT % |
5.65
(0.855)
|
5.19
(0.766)
|
15.55
(1.726)
|
17.66
(1.985)
|
| Hi CD16CD56 % |
1.05
(0.183)
|
0.93
(0.145)
|
5.29
(1.296)
|
6.20
(1.423)
|
| CD8+IL4+ % (in CD8+) |
5.64
(3.74)
|
1.87
(0.538)
|
3.13
(0.964)
|
1.91
(1.225)
|
Adverse Events
| Time Frame | 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. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Only patients who received at least one dose of the investigational drug (N=66) were included in the data set used for safety. | |||
| Arm/Group Title | Fingolimod 0.5 mg | All Patients | ||
| Arm/Group Description | Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od. | All patients in the trial | ||
All Cause Mortality |
||||
| Fingolimod 0.5 mg | All Patients | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/66 (0%) | 0/66 (0%) | ||
Serious Adverse Events |
||||
| Fingolimod 0.5 mg | All Patients | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/66 (4.5%) | 3/66 (4.5%) | ||
| Cardiac disorders | ||||
| Sinus bradycardia | 2/66 (3%) | 2/66 (3%) | ||
| Infections and infestations | ||||
| Herpes zoster | 1/66 (1.5%) | 1/66 (1.5%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Fingolimod 0.5 mg | All Patients | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/66 (10.6%) | 7/66 (10.6%) | ||
| Infections and infestations | ||||
| Influenza | 2/66 (3%) | 2/66 (3%) | ||
| Investigations | ||||
| Gamma-glutamyltransferase increased | 1/66 (1.5%) | 1/66 (1.5%) | ||
| Lymphocyte count decreased | 1/66 (1.5%) | 1/66 (1.5%) | ||
| White blood cell count decreased | 1/66 (1.5%) | 1/66 (1.5%) | ||
| Nervous system disorders | ||||
| Headache | 1/66 (1.5%) | 1/66 (1.5%) | ||
| Muscle contractions involuntary | 1/66 (1.5%) | 1/66 (1.5%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
| Novartis.email.@novartis.com |
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02373098
Other Study ID Numbers:
- CFTY720DTR04
First Posted:
Feb 26, 2015
Last Update Posted:
Sep 30, 2019
Last Verified:
Sep 1, 2019