Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| FTY720 | Experimental |
| |
| Healthy volunteers | No Intervention | Healthy volunteers with no intervention or drug administered. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fingolimod 0.5 mg | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA | Blood samples were taken at baseline and measurements were performed before treatment of fingolimod. | Baseline |
| Baseline Flow Cytometry Analyses for Blood Cytokines and Chemokines in Healthy Controls and RRMS Patients | baseline peripheral blood flow cytometric analysis in study participants | Baseline |
| Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | Baseline peripheral blood flow cytometric analyses in study participants evaluated by flow cytometry analysis. | Baseline |
| Measure | Description | Time Frame |
|---|---|---|
| Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | Change of serum cytokine and chemokine levels measured by ELISA in RRMS patients treated with fingolimod between visits | Baseline, month 3, month 6 |
| Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and RRMS Patients |
Not provided
Key Inclusion Criteria:
Key Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Mecidiyeköy | Istanbul | 34394 | Turkey (Türkiye) | ||
| Novartis Investigative Site |
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.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | FTY720 | Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od. |
| FG001 | Healthy Volunteers | The healthy volunteers had only Visit 1 (Day 0) and served as control group for cytokine/chemokine measurements |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety set
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | FTY720 | Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od. |
| BG001 | Healthy Volunteers | The healthy volunteers had only Visit 1 (Day 0) and served as control group for cytokine/chemokine measurements |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Baseline Serum Cytokine and Chemokine Levels of Healthy Controls and RRMS Patients - ELISA | Blood samples were taken at baseline and measurements were performed before treatment of fingolimod. | Intent to treat | Posted | Mean | Standard Error | pg/ml | Baseline |
|
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.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Fingolimod 0.5 mg | Relapsing-remitting multiple sclerosis (RRMS) patients were treated with fingolimod 0.5 mg capsule od. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sinus bradycardia | Cardiac disorders | MedDRA (21.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Influenza | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 | Novartis.email.@novartis.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 21, 2016 | Oct 4, 2018 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 30, 2017 | Oct 4, 2018 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D020529 | Multiple Sclerosis, Relapsing-Remitting |
| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000068876 | Fingolimod Hydrochloride |
| ID | Term |
|---|---|
| D013110 | Sphingosine |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
Not provided
Not provided
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 Patients
Not provided
Not provided
Not provided
Not provided
Peripheral blood chemokine cytokine levels measured by flow cytometry during fingolimod treatment in healthy controls at baseline and in RRMS patients between visits |
| Baseline, Month 3, Month 6 |
| Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and 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. | Baseline, Month 3, Month 6 |
| Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and 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 | Baseline, Month 3, Month 6 |
| Üsküdar |
| Istanbul |
| 34668 |
| Turkey (Türkiye) |
| Novartis Investigative Site | Istanbul | 34093 | Turkey (Türkiye) |
| Withdrawal by Subject |
|
| Adverse Event |
|
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
| Primary | Baseline Flow Cytometry Analyses for Blood Cytokines and Chemokines in Healthy Controls and RRMS Patients | baseline peripheral blood flow cytometric analysis in study participants | Analysis was done in the healthy volunteers and RRMS patients. | Posted | Mean | Standard Error | absolute cell count | Baseline |
|
|
|
|
| Secondary | Serum Cytokine and Chemokine Levels inRRMS Patients Between Visits | Change of serum cytokine and chemokine levels measured by ELISA in RRMS patients treated with fingolimod between visits | Intent to treat | Posted | Mean | Standard Error | pg/ml | Baseline, month 3, month 6 |
|
|
|
| Secondary | Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and 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 | Intent to treat. Data analyzed in RRMS patients. | Posted | Mean | Standard Error | pg/ml | Baseline, Month 3, Month 6 |
|
|
|
| Primary | Percent Blood Cytokines and Chemokines Via Flow Cytometry Analyses of Healthy Controls and RRMS Patients at Baseline | Baseline peripheral blood flow cytometric analyses in study participants evaluated by flow cytometry analysis. | Analysis was done in the healthy volunteers and RRMS patients. | Posted | Mean | Standard Error | Percent of cells | Baseline |
|
|
|
|
| Secondary | Absolute Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and 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. | Intent to treat. Data analyzed in RRMS patients. | Posted | Mean | Standard Error | absolute cell count | Baseline, Month 3, Month 6 |
|
|
|
| Secondary | Percent of Peripheral Blood Cytokine and Chemokine Measurements in Healthy Controls and 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 | Intent to treat. Data analyzed in RRMS patients. | Posted | Mean | Standard Error | percent of cell count | Baseline, Month 3, Month 6 |
|
|
|
| 0 |
| 66 |
| 3 |
| 66 |
| 7 |
| 66 |
| EG001 | All Patients | All patients in the trial | 0 | 66 | 3 | 66 | 7 | 66 |
| Herpes zoster | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA (21.0) | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | MedDRA (21.0) | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA (21.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
|
| Muscle contractions involuntary | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
|
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.
| D003711 | Demyelinating Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D011409 |
| Propylene Glycols |
| D006018 | Glycols |
| D000588 | Amines |
| NK abs |
|
| NKT abs |
|
| Hi CD16CD56 abs |
|
| CD4CD25 (CD3 gate) |
|
| Hi CD4CD25 (CD3 gate) |
|
| 0.587 |
| Other |
| NK abs | Wilcoxon (Mann-Whitney) | 0.300 | Other |
| NKT abs | Wilcoxon (Mann-Whitney) | 0.096 | Other |
| Hi CD16CD56 abs | Wilcoxon (Mann-Whitney) | 0.270 | Other |
| CD4CD25 | Wilcoxon (Mann-Whitney) | 0.902 | Other |
| Hi CD4CD25 | Wilcoxon (Mann-Whitney) | 0.283 | Other |
|
| IL8 |
|
| IL13 |
|
| CCL5= RANTES |
|
| IL23 |
|
| VLA4 |
|
| CXCL10=IP-10 (CXCR3 ligand) |
|
| CCL2=MCP-1 |
|
| IL4 |
|
| IL17A |
|
| TNF |
|
| IL22 |
|
| CD19 abs |
|
| NK abs |
|
| NKT abs |
|
| Hi CD16CD56 abs |
|
| CD4CD25 (CD3 gate) |
|
| Hi CD4CD25 (CD3 gate) |
|
| NK % |
|
| NKT % |
|
| Hi CD16CD56 % |
|
| CD3CD4 % (Lymphogate) |
|
| CD3CD8 % (Lymphogate) |
|
| CD3CD4 % (CD3 gate) |
|
| CD3CD8 % (CD3 gate) |
|
| CD4+IFNg+ (in CD4+) |
|
| CD4+IL17+ (in CD4+) |
|
| CD8+IFNg+ (in CD8+) |
|
| CD8+IL17+ (in CD8+) |
|
| IFNg+ (in CD4+CD25+) |
|
| IL17+ (in CD4+CD25+) |
|
| CD4+IL10+ (in CD4+) |
|
| CD4+IL4+ (in CD4+) |
|
| CD4-CD8-IL4+ (in CD4-CD8-) |
|
| CD8+IL10+ (in CD8+) |
|
| CD8+IL4+ % (in CD8+) |
|
| IL10+ (in CD4+CD25+) |
|
| IL4+ (in CD4+CD25+) |
|
| CD4+TNFa+ (in CD4+) |
|
| CD4+IL9+ (in CD4+) |
|
| CD8+TNFa+ (in CD8+) |
|
| CD8+IL9+ (in CD8+) |
|
| TNFa+ (in CD4+CD25+) |
|
| IL9+ (in CD4+CD25+) |
|
| 0.300 |
| Other |
| NK % | Wilcoxon (Mann-Whitney) | 0.657 | Other |
| NKT % | Wilcoxon (Mann-Whitney) | 0.439 | Other |
| Hi CD16CD56 % | Wilcoxon (Mann-Whitney) | 0.449 | Other |
| CD3CD4 | Wilcoxon (Mann-Whitney) | 0.356 | Other |
| CD3CD8 | Wilcoxon (Mann-Whitney) | 0.787 | Other |
| CD3CD4 | Wilcoxon (Mann-Whitney) | 0.121 | Other |
| CD3CD8 | Wilcoxon (Mann-Whitney) | 0.209 | Other |
| CD4+IFNg+ (in CD4+) | Wilcoxon (Mann-Whitney) | 0.069 | Other |
| CD4+IL17+ (in CD4+) | Wilcoxon (Mann-Whitney) | 0.402 | Other |
| CD8+IFNg+ (in CD8+) | Wilcoxon (Mann-Whitney) | 0.017 | Other |
| CD8+IL17+ (in CD8+) | Wilcoxon (Mann-Whitney) | 0.017 | Other |
| IFNg+ (in CD4+CD25+) | Wilcoxon (Mann-Whitney) | 0.026 | Other |
| IL17+ (in CD4+CD25+) | Wilcoxon (Mann-Whitney) | 0.168 | Other |
| CD4+IL10+ (in CD4+) | Wilcoxon (Mann-Whitney) | 0.004 | Other |
| CD4+IL4+ (in CD4+) | Wilcoxon (Mann-Whitney) | 0.013 | Other |
| CD4-CD8-IL4+ (in CD4-CD8-) | Wilcoxon (Mann-Whitney) | 0.171 | Other |
| CD8+IL10+ (in CD8+) | Wilcoxon (Mann-Whitney) | 0.013 | Other |
| CD8+IL4+ (in CD8+) | Wilcoxon (Mann-Whitney) | 0.013 | Other |
| IL10+ (in CD4+CD25+) | Wilcoxon (Mann-Whitney) | 0.007 | Other |
| IL4+ (in CD4+CD25+) | Wilcoxon (Mann-Whitney) | 0.001 | Other |
| CD4+TNFa+ (in CD4+) | Wilcoxon (Mann-Whitney) | 0.002 | Other |
| CD4+IL9+ (in CD4+) | Wilcoxon (Mann-Whitney) | 0.107 | Other |
| CD8+TNFa+ (in CD8+) | Wilcoxon (Mann-Whitney) | 0.000 | Other |
| CD8+IL9+ (in CD8+) | Wilcoxon (Mann-Whitney) | 0.022 | Other |
| TNFa+ (in CD4+CD25+) | Wilcoxon (Mann-Whitney) | 0.001 | Other |
| IL9+ (in CD4+CD25+) | Wilcoxon (Mann-Whitney) | 0.127 | Other |
| CD3CD8 (Lymphogate) |
|
| CD3CD4 (CD3 gate) |
|
| CD3CD8 (CD3 gate) |
|
| CD4+IFNg+ (in CD4+) |
|
| CD4+IL17+ (in CD4+) |
|
| CD8+IFNg+ (in CD8+) |
|
| CD8+IL17+ (in CD8+) |
|
| IFNg+ (in CD4+CD25+) |
|
| IL17+ (in CD4+CD25+) |
|
| CD4+IL10+ (in CD4+) |
|
| CD4+IL4+ (in CD4+) |
|
| CD4-CD8-IL4+ (in CD4-CD8-) |
|
| CD8+IL10+ (in CD8+) |
|
| IL10+ (in CD4+CD25+) |
|
| IL4+ (in CD4+CD25+) |
|
| CD4+TNFa+ (in CD4+) |
|
| CD4+IL9+ (in CD4+) |
|
| CD8+TNFa+ (in CD8+) |
|
| CD8+IL9+ (in CD8+) |
|
| TNFa+ (in CD4+CD25+) |
|
| IL9+ (in CD4+CD25+) |
|
| CD19 % |
|
| NK % |
|
| NKT % |
|
| Hi CD16CD56 % |
|
| CD8+IL4+ % (in CD8+) |
|