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A Study of Immune Phenotype Biomarkers in Patients With Relapsing Multiple Sclerosis (RMS) After Treatment With 0.5mg Fingolimod (FLUENT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03257358
Recruitment Status : Completed
First Posted : August 22, 2017
Results First Posted : July 21, 2020
Last Update Posted : October 7, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Basic Science
Condition Relapsing Multiple Sclerosis
Intervention Drug: Fingolimod
Enrollment 382
Recruitment Details  
Pre-assignment Details 165 patients were enrolled but only 163 were treated and included in the Safety Set
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Period Title: Overall Study
Started 165 217
Never Received Treatment 2 0
Completed 94 183
Not Completed 71 34
Reason Not Completed
Adverse Event             25             12
Lack of Efficacy             1             1
Lost to Follow-up             12             4
Non-compliance with fingolimod treatment             4             2
Physician Decision             2             2
Protocol Violation             5             3
Technical problems             4             1
Withdrawal by Subject             8             3
Withdrawal of informed consent             9             5
New therapy for study indication             1             0
No longer requires treatment             0             1
Arm/Group Title Cohort 1 Cohort 2 Total
Hide Arm/Group Description RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years Total of all reporting groups
Overall Number of Baseline Participants 163 217 380
Hide Baseline Analysis Population Description
There were 165 participants enrolled in the trial but 2 participants in Cohort 1 never received treatment
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 163 participants 217 participants 380 participants
41.8  (10.72) 48.9  (9.94) 45.9  (10.86)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 163 participants 217 participants 380 participants
Female
127
  77.9%
158
  72.8%
285
  75.0%
Male
36
  22.1%
59
  27.2%
95
  25.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Caucasian Number Analyzed 163 participants 217 participants 380 participants
136 186 322
Black Number Analyzed 163 participants 217 participants 380 participants
22 22 44
Asian Number Analyzed 163 participants 217 participants 380 participants
0 3 3
Native American Number Analyzed 163 participants 217 participants 380 participants
1 2 3
Unknown Number Analyzed 163 participants 217 participants 380 participants
3 1 4
Other Number Analyzed 163 participants 217 participants 380 participants
1 3 4
Time from Multiple Sclerosis Diagnosis until study treamtent  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 163 participants 217 participants 380 participants
6.78  (7.984) 12.94  (7.007) 10.30  (8.033)
Number of Patients with Relaspses within the last year   [1] 
Measure Type: Number
Unit of measure:  Number of patients with relapse
Number of patients with at least 1 relapse Number Analyzed 162 participants 215 participants 377 participants
101 32 133
Number of patients with no relapse Number Analyzed 162 participants 215 participants 377 participants
61 183 244
[1]
Measure Analysis Population Description: Missing data for some participants
1.Primary Outcome
Title Change From Baseline to Month 6 in CD4+ Naive T Cells (CCR7+ CD45RA+)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:
RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=147,188 Number Analyzed 147 participants 188 participants
404.4  (273.56) 3.4  (20.69)
Month 6 n=97,156 Number Analyzed 97 participants 156 participants
7.6  (38.04) 4.8  (23.52)
Change from BL to Month 6, n=97,156 Number Analyzed 97 participants 156 participants
-411.4  (273.31) 0.8  (25.12)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value -413.4
Confidence Interval (2-Sided) 95%
-422.7 to -404.
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-3.9 to 3.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.91
Estimation Comments [Not Specified]
2.Primary Outcome
Title Change From Baseline to Month 6 in CD4+ Central Memory T Cells (CCR7+CD45RA-CD45RO+)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:
RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=147,188 Number Analyzed 147 participants 188 participants
374.6  (216.36) 16.3  (45.11)
Month 6 n=97,156 Number Analyzed 97 participants 156 participants
19.6  (58.77) 18.3  (42.89)
Change from BL to Month 6, n=97,156 Number Analyzed 97 participants 156 participants
-368.9  (218.40) 1.1  (51.29)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value -368.7
Confidence Interval (2-Sided) 95%
-382.8 to 354.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 7.08
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-7.1 to 6.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.54
Estimation Comments [Not Specified]
3.Primary Outcome
Title Change From Baseline to Month 6 in CD4+ Effector Memory T Cells (CCR7-CD45RA-CD45RO+)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:
RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=147,188 Number Analyzed 147 participants 188 participants
74.3  (43.56) 22.8  (41.21)
Month 6, n=97,156 Number Analyzed 97 participants 156 participants
18.2  (23.00) 21.7  (33.28)
Change from BL to Month 6 n=97,156 Number Analyzed 97 participants 156 participants
-51.5  (36.24) -2.0  (31.86)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value -52.1
Confidence Interval (2-Sided) 95%
-57.2 to -46.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.58
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value -3.1
Confidence Interval (2-Sided) 95%
-7.6 to 1.4
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.27
Estimation Comments [Not Specified]
4.Primary Outcome
Title Change From Baseline to Month 6 in CD4+ Th1 Cells (CXCR3+)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:
RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=148,211 Number Analyzed 148 participants 211 participants
53.8  (38.29) 11.1  (31.90)
Month 6 n=104,180 Number Analyzed 104 participants 180 participants
7.6  (15.12) 11.7  (33.33)
Change from BL to Month 6 n=104,180 Number Analyzed 104 participants 180 participants
-43.6  (32.51) -0.7  (14.38)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value -43.6
Confidence Interval (2-Sided) 95%
-46.9 to -40.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.67
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-3.0 to 1.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.18
Estimation Comments [Not Specified]
5.Primary Outcome
Title Change From Baseline to Month 6 in CD4+ Th2 Cells (CCR4+)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:
RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=148,212 Number Analyzed 148 participants 212 participants
35.9  (30.06) 1.1  (4.01)
Month 6 n=104,181 Number Analyzed 104 participants 181 participants
1.7  (4.17) 1.6  (5.55)
Change from BL to Month 6 n=104,181 Number Analyzed 104 participants 181 participants
-36.1  (32.42) 0.5  (5.28)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value -36.3
Confidence Interval (2-Sided) 95%
-37.2 to -35.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.48
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-0.4 to 1.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.42
Estimation Comments [Not Specified]
6.Primary Outcome
Title Change From Baseline to Month 6 in CD4+ Th17 Cells (CCR6+)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:
RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=148,212 Number Analyzed 148 participants 212 participants
55.5  (36.60) 2.4  (5.96)
Month 6 n=104,181 Number Analyzed 104 participants 181 participants
3.1  (8.38) 2.8  (6.91)
Change from BL to Month 6 n=104,181 Number Analyzed 104 participants 181 participants
-53.2  (39.01) 0.5  (6.77)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value -53.2
Confidence Interval (2-Sided) 95%
-55.1 to -51.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.97
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-0.7 to 1.4
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.51
Estimation Comments [Not Specified]
7.Primary Outcome
Title Change From Baseline to Month 6 in CD8+ Naive T Cells (CCR7+CD45RA+)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:
RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=147,188 Number Analyzed 147 participants 188 participants
150.9  (119.48) 1.8  (8.87)
Month 6 n=97,156 Number Analyzed 97 participants 156 participants
4.2  (22.00) 3.3  (15.84)
Change from BL to Month 6 n=97,156 Number Analyzed 97 participants 156 participants
-139.3  (113.25) 1.2  (14.89)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value -140.4
Confidence Interval (2-Sided) 95%
-145.8 to -135.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.71
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
-1.9 to 3.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.30
Estimation Comments [Not Specified]
8.Primary Outcome
Title Change From Baseline to Month 6 in CD8+ Central Memory T Cells (CCR7+CD45RA-CD45RO+)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:
RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=147,188 Number Analyzed 147 participants 188 participants
93.1  (75.22) 5.6  (14.85)
Month 6 n=97,156 Number Analyzed 97 participants 156 participants
5.9  (16.42) 6.1  (12.97)
Change from BL to Month 6 n=97,156 Number Analyzed 97 participants 156 participants
-85.2  (67.95) 0.0  (15.92)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value -85.2
Confidence Interval (2-Sided) 95%
-89.0 to -81.4
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.92
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-2.3 to 1.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.06
Estimation Comments [Not Specified]
9.Primary Outcome
Title Change From Baseline to Month 6 in CD8+ Effector Memory T Cells (CCR7-CD45RA-CD45RO+)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:
RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=147,188 Number Analyzed 147 participants 188 participants
108.2  (93.28) 63.8  (115.28)
Month 6 n=97,156 Number Analyzed 97 participants 156 participants
55.4  (102.88) 52.6  (40.76)
Change from BL to Month 6 n=97,156 Number Analyzed 97 participants 156 participants
-40.6  (103.03) -12.5  (116.16)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value -27.9
Confidence Interval (2-Sided) 95%
-51.1 to -4.8
Parameter Dispersion
Type: Standard Error of the Mean
Value: 11.65
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value -9.4
Confidence Interval (2-Sided) 95%
-16.3 to -2.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.47
Estimation Comments [Not Specified]
10.Primary Outcome
Title Change From Baseline to Month 6 in Naive B Lymphocytes (CD19+CD27-)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:
RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=144,212 Number Analyzed 144 participants 212 participants
201.1  (134.16) 18.1  (33.79)
Month 6 n=101,176 Number Analyzed 101 participants 176 participants
15.0  (10.50) 17.8  (19.99)
Change from BL to Month 6 n=101,176 Number Analyzed 101 participants 176 participants
-181.4  (125.71) -0.2  (36.61)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value -181.2
Confidence Interval (2-Sided) 95%
-183.3 to -179.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.07
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-4.1 to 2.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.66
Estimation Comments [Not Specified]
11.Primary Outcome
Title Change From Baseline to Month 6 in Memory B Lymphocytes (CD19+CD27+)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:
RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=144,212 Number Analyzed 144 participants 212 participants
61.8  (74.29) 3.3  (22.58)
Month 6 n=101,176 Number Analyzed 101 participants 176 participants
3.8  (6.24) 4.0  (21.18)
Change from BL to Month 6 n=101,176 Number Analyzed 101 participants 176 participants
-55.1  (74.36) 0.3  (6.40)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value -55.2
Confidence Interval (2-Sided) 95%
-56.5 to -53.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.66
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.5 to 1.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.42
Estimation Comments [Not Specified]
12.Primary Outcome
Title Change From Baseline to Month 6 in Regulatory B Lymphocytes (CD19+CD24+CD38+)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:
RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=144,212 Number Analyzed 144 participants 212 participants
12.3  (12.88) 5.3  (7.66)
Month 6 n=101,176 Number Analyzed 101 participants 176 participants
4.8  (3.92) 6.1  (5.16)
Change from BL to Month 6 n=101,176 Number Analyzed 101 participants 176 participants
-7.4  (10.64) 0.9  (8.15)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value -7.2
Confidence Interval (2-Sided) 95%
-8.0 to -6.4
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.40
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value 1.1
Confidence Interval (2-Sided) 95%
0.3 to 2.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.43
Estimation Comments [Not Specified]
13.Primary Outcome
Title Change From Baseline to Month 6 in Monocytes (CD14+)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:
RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=150,197 Number Analyzed 150 participants 197 participants
329.6  (167.52) 251.7  (118.46)
Month 6 n=105,166 Number Analyzed 105 participants 166 participants
384.7  (148.76) 379.2  (131.42)
Change from BL to Month 6 n=105,166 Number Analyzed 105 participants 166 participants
66.1  (139.24) 123.1  (123.85)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value 69.4
Confidence Interval (2-Sided) 95%
42.1 to 96.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 13.78
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value 117.0
Confidence Interval (2-Sided) 95%
97.1 to 136.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 10.07
Estimation Comments [Not Specified]
14.Primary Outcome
Title Change From Baseline to Month 6 in Neutrophils (CD16+)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:
RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=149,197 Number Analyzed 149 participants 197 participants
4041.4  (1576.73) 3717.9  (1552.87)
Month 6 n=105,166 Number Analyzed 105 participants 166 participants
3505.4  (1512.81) 3312.6  (1311.04)
Change from BL to Month 6 n=105,166 Number Analyzed 105 participants 166 participants
-586.0  (1463.26) -439.6  (1274.80)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value -782.6
Confidence Interval (2-Sided) 95%
-1058.2 to -507.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 138.90
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value -485.9
Confidence Interval (2-Sided) 95%
-667.3 to -304.4
Parameter Dispersion
Type: Standard Error of the Mean
Value: 91.88
Estimation Comments [Not Specified]
15.Primary Outcome
Title Change From Baseline to Month 6 in NK Cells (CD56+)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:
RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=149,197 Number Analyzed 149 participants 197 participants
166.4  (98.23) 181.0  (113.95)
Month 6 n=105,166 Number Analyzed 105 participants 166 participants
133.6  (83.41) 154.5  (88.99)
Change from BL to Month 6 n=105,166 Number Analyzed 105 participants 166 participants
-29.4  (76.42) -28.0  (81.73)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value -33.3
Confidence Interval (2-Sided) 95%
-48.2 to -18.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 7.47
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value -25.8
Confidence Interval (2-Sided) 95%
-36.7 to -14.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.52
Estimation Comments [Not Specified]
16.Primary Outcome
Title Change From Baseline to Month 6 in Total CD4+ Absolute Cell Count
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:
RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=156,213 Number Analyzed 156 participants 213 participants
936.3  (443.31) 64.4  (122.56)
Month 6 n=110,182 Number Analyzed 110 participants 182 participants
53.4  (114.61) 71.3  (112.50)
Change from BL to Month 6 n=110,182 Number Analyzed 110 participants 182 participants
-884.1  (440.65) 1.4  (105.17)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value -888.7
Confidence Interval (2-Sided) 95%
-914.6 to -862.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 13.10
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value -3.3
Confidence Interval (2-Sided) 95%
-17.6 to 11.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 7.24
Estimation Comments [Not Specified]
17.Primary Outcome
Title Change From Baseline to Month 6 in Total CD4+ Differential Cell Count
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:
RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=157,213 Number Analyzed 157 participants 213 participants
49.40  (10.115) 11.95  (12.637)
Month 6 n=111,183 Number Analyzed 111 participants 183 participants
11.08  (9.875) 12.82  (13.687)
Change from BL to Month 6 n=111,183 Number Analyzed 111 participants 183 participants
-39.09  (12.052) 0.32  (6.119)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value -39.50
Confidence Interval (2-Sided) 95%
-41.59 to -37.42
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.053
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value 0.14
Confidence Interval (2-Sided) 95%
-0.87 to 1.14
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.510
Estimation Comments [Not Specified]
18.Primary Outcome
Title Change From Baseline to Month 6 in Total CD8+ Absolute Cell Count
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:
RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=156,213 Number Analyzed 156 participants 213 participants
419.9  (257.71) 124.6  (213.41)
Month 6 n=110,182 Number Analyzed 110 participants 182 participants
120.1  (148.82) 116.8  (101.44)
Change from BL to Month 6 n=110,182 Number Analyzed 110 participants 182 participants
-266.2  (209.45) -13.5  (205.59)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value -248.9
Confidence Interval (2-Sided) 95%
-278.7 to -219.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 15.00
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value -9.9
Confidence Interval (2-Sided) 95%
-25.1 to 5.4
Parameter Dispersion
Type: Standard Error of the Mean
Value: 7.71
Estimation Comments [Not Specified]
19.Primary Outcome
Title Change From Baseline to Month 6 in Total CD8+ Differential Cell Counts (%)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:
RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=157,213 Number Analyzed 157 participants 213 participants
21.86  (7.852) 25.25  (14.406)
Month 6 n=111,183 Number Analyzed 111 participants 183 participants
25.33  (14.998) 24.99  (13.863)
Change from BL to Month 6 Number Analyzed 111 participants 183 participants
4.63  (11.327) -0.39  (4.528)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value 5.60
Confidence Interval (2-Sided) 95%
3.13 to 8.08
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.249
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
-0.68 to 0.76
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.364
Estimation Comments [Not Specified]
20.Primary Outcome
Title Change From Baseline to Month 6 in Total CD19+ Absolute Cell Count
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:
RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=151,213 Number Analyzed 151 participants 213 participants
259.7  (167.94) 21.4  (45.19)
Month 6 n=106,179 Number Analyzed 106 participants 179 participants
19.5  (15.91) 21.8  (34.75)
Change from BL to Month 6 n=106,179 Number Analyzed 106 participants 179 participants
-231.3  (153.49) 0.1  (40.66)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value -231.0
Confidence Interval (2-Sided) 95%
-234.5 to -227.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.75
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-5.2 to 4.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.45
Estimation Comments [Not Specified]
21.Primary Outcome
Title Change From Baseline to Month 6 in Total CD19+ Differential Cell Count (%)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:
RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=152,213 Number Analyzed 152 participants 213 participants
13.97  (7.245) 4.81  (5.294)
Month 6 n=107,180 Number Analyzed 107 participants 180 participants
5.38  (4.368) 4.83  (5.236)
Change from BL to Month 6 n=107,180 Number Analyzed 107 participants 180 participants
-8.53  (6.723) 0.23  (3.027)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value -8.30
Confidence Interval (2-Sided) 95%
-9.21 to -7.40
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.455
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2
Comments [Not Specified]
Type of Statistical Test Other
Comments Estimation
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter least squares mean
Estimated Value 0.32
Confidence Interval (2-Sided) 95%
-0.17 to 0.82
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.251
Estimation Comments [Not Specified]
22.Secondary Outcome
Title Change From Baseline to Month 12 in CD4+ Naive T Cells (CCR7+CD45RA+)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:
RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=147,188 Number Analyzed 147 participants 188 participants
404.4  (273.56) 3.4  (20.69)
Change from BL to Month 12 n=82,150 Number Analyzed 82 participants 150 participants
-376.3  (277.23) -0.8  (20.10)
23.Secondary Outcome
Title Change From Baseline to Month 12 in CD4+ Central Memory T Cells (CCR7+CD45RA-CD45RO+)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:
RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=147,188 Number Analyzed 147 participants 188 participants
374.6  (216.36) 16.3  (45.11)
Change from BL to Month 12 n=83,150 Number Analyzed 83 participants 150 participants
-356.8  (237.76) 3.9  (55.06)
24.Secondary Outcome
Title Change From Baseline to Month 12 in CD4+ Effector Memory T Cells (CCR7-CD45RA-CD45RO+)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:
RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=147,188 Number Analyzed 147 participants 188 participants
74.3  (43.56) 22.8  (41.21)
Change from BL to Month 12 n=83,150 Number Analyzed 83 participants 150 participants
-50.4  (40.40) -3.3  (30.24)
25.Secondary Outcome
Title Change From Baseline to Month 12 in CD4+ Th1 Cells (CXCR3+)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:
RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=148,211 Number Analyzed 148 participants 211 participants
53.8  (38.29) 11.1  (31.90)
Change from BL to Month 12 n=88,175 Number Analyzed 88 participants 175 participants
-42.3  (38.9) -2.1  (15.04)
26.Secondary Outcome
Title Change From Baseline to Month 12 in CD4+ Th2 Cells (CCR4+)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:
RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=148,212 Number Analyzed 148 participants 212 participants
35.9  (30.06) 1.1  (4.01)
Change from BL to Month 12 Number Analyzed 88 participants 175 participants
-36.3  (34.63) 0.4  (4.93)
27.Secondary Outcome
Title Change From Baseline to Month 12 in CD4+ Th17 Cells (CCR6+)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description:
RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=148,212 Number Analyzed 148 participants 212 participants
55.5  (36.60) 2.4  (5.96)
Change from BL to Month 12 n=88,175 Number Analyzed 88 participants 175 participants
-52.1  (41.20) 0.5  (7.70)
28.Secondary Outcome
Title Change From Baseline to Month 12 in CD8+ Naive T Cells (CCR7+CD45RA+)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 12
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Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
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RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=147,188 Number Analyzed 147 participants 188 participants
150.9  (119.48) 1.8  (8.87)
Change from BL to Month 12 n=83,150 Number Analyzed 83 participants 150 participants
-126.3  (103.38) 0.6  (10.24)
29.Secondary Outcome
Title Change From Baseline to Month 12 in CD8+ Central Memory T Cells (CCR7+CD45RA-CD45RO+)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 12
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Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
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RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=147,188 Number Analyzed 147 participants 188 participants
93.1  (75.22) 5.6  (14.85)
Change from BL to Month 12 n=83,150 Number Analyzed 83 participants 150 participants
-86.5  (75.75) 0.0  (16.88)
30.Secondary Outcome
Title Change From Baseline to Month 12 in CD8+ Effector Memory T Cells (CCR7-CD45RA-CD45RO+)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 12
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Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
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RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=147,188 Number Analyzed 147 participants 188 participants
108.2  (93.28) 63.8  (115.28)
Change from BL to Month 12 n=83,150 Number Analyzed 83 participants 150 participants
-55.9  (57.48) -15.9  (122.31)
31.Secondary Outcome
Title Change From Baseline to Month 12 in Naive B Lymphocytes (CD19+CD27-)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 12
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Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
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RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=144,212 Number Analyzed 144 participants 212 participants
201.11  (134.16) 18.1  (33.79)
Change from BL to Month 12 n=82,174 Number Analyzed 82 participants 174 participants
-177.0  (114.43) -0.5  (40.72)
32.Secondary Outcome
Title Change From Baseline to Month 12 in Memory B Lymphocytes (CD19+CD27+)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 12
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Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
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RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=144,212 Number Analyzed 144 participants 212 participants
61.8  (74.29) 3.3  (22.58)
Change from BL to Month 12 n=82,174 Number Analyzed 82 participants 174 participants
-46.4  (39.15) 1.4  (19.59)
33.Secondary Outcome
Title Change From Baseline to Month 12 in Regulatory B Lymphocytes (CD19+CD24+CD38+)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 12
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Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
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RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=144,212 Number Analyzed 144 participants 212 participants
12.3  (12.88) 5.3  (7.66)
Change from BL to Month 12 n=82,174 Number Analyzed 82 participants 174 participants
-7.7  (11.60) 0.8  (8.88)
34.Secondary Outcome
Title Change From Baseline to Month 12 in Monocytes (CD14+)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 12
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Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
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RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=150,197 Number Analyzed 150 participants 197 participants
329.6  (167.52) 251.7  (118.46)
Change from BL to Month 12 n=86,164 Number Analyzed 86 participants 164 participants
57.1  (139.91) 112.4  (130.82)
35.Secondary Outcome
Title Change From Baseline to Month 12 in Neutrophils (CD16+)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 12
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Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
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RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=149,197 Number Analyzed 149 participants 197 participants
4041.4  (1576.73) 3717.9  (1552.87)
Change from BL to Month 12 n=87, 164 Number Analyzed 87 participants 164 participants
-815.9  (1368.23) -345.0  (1253.29)
36.Secondary Outcome
Title Change From Baseline to Month 12 in NK Cells (CD56+)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 12
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Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
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RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=149,197 Number Analyzed 149 participants 197 participants
166.4  (98.23) 181.0  (113.95)
Change from BL to Month 12 n=87,164 Number Analyzed 87 participants 164 participants
-32.6  (97.86) -28.9  (86.71)
37.Secondary Outcome
Title Change From Baseline to Month 12 in Total CD4+ Absolute Cell Count
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 12
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Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
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RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=156,213 Number Analyzed 156 participants 213 participants
936.3  (443.31) 64.4  (122.56)
Change from BL to Month 12 n=94,176 Number Analyzed 94 participants 176 participants
-844.9  (439.92) 0.7  (101.82)
38.Secondary Outcome
Title Change From Baseline to Month 12 in Total CD4+ Differential Cell Count (%)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 12
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Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
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RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=157,213 Number Analyzed 157 participants 213 participants
49.40  (10.115) 11.95  (12.637)
Change from BL to Month 12 n=95,176 Number Analyzed 95 participants 176 participants
-37.90  (12.756) 0.70  (6.127)
39.Secondary Outcome
Title Change From Baseline to Month 12 in Total CD8+ Absolute Cell Count
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 12
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Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
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RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=156,213 Number Analyzed 156 participants 213 participants
419.9  (257.71) 124.6  (213.41)
Change from BL to Month 12 n=94,176 Number Analyzed 94 participants 176 participants
-265.1  (168.81) -11.6  (216.00)
40.Secondary Outcome
Title Change From Baseline to Month 12 in Total CD8+ Differential Cell Counts (%)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 12
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Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
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RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=157,213 Number Analyzed 157 participants 213 participants
21.86  (7.852) 25.25  (14.406)
Change from BL to Month 12 n=95,176 Number Analyzed 95 participants 176 participants
4.33  (11.185) 0.34  (5.150)
41.Secondary Outcome
Title Change From Baseline to Month 12 in Total CD19+ Absolute Cell Count
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 12
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Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
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RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=151,213 Number Analyzed 151 participants 213 participants
259.7  (167.94) 21.4  (45.19)
Change from BL to Month 12 n=88,176 Number Analyzed 88 participants 176 participants
-218.9  (127.69) 1.0  (52.35)
42.Secondary Outcome
Title Change From Baseline to Month 12 in Total CD19+ Differential Cell Count (%)
Hide Description Blood samples (approximately 60-80 ml) were collected at specifiied visits for biomarker and hematology assessments. In Cohort 1 patients it was critical that the blood sample was collected prior to administration of fingolimod, first dose observation (FDO). A central laboratory was used for analysis of all specimens collected.
Time Frame Baseline to Month 12
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Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
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RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=152,213 Number Analyzed 152 participants 213 participants
13.97  (7.245) 4.81  (5.294)
Change from BL to Month 12 n=89,176 Number Analyzed 89 participants 176 participants
-8.86  (7.222) 0.20  (3.210)
43.Secondary Outcome
Title Multiple Sclerosis (MS) Relapses During Treatment
Hide Description A relapse is defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (<37.5°C) or infection.
Time Frame Baseline to Month 12
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Arm/Group Title Cohort 1 Cohort 2
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RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Measure Type: Number
Unit of Measure: relapses
Number of patients with relapses 11 13
Total number of relapses 12 13
Relapses not requiring steroid use 5 5
Relapses requiring steroid use 7 8
Mild relapse 5 8
Moderate relapse 6 5
Severe relapse 1 0
44.Secondary Outcome
Title Number of Participants Who Received Steroid Treatment for MS Relapses During Treatment
Hide Description A relapse is defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (<37.5°C) or infection.
Time Frame Baseline to Month 12
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Arm/Group Title Cohort 1 Cohort 2
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RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Measure Type: Count of Participants
Unit of Measure: Participants
Patients with ≥ 1 relapses
11
   6.7%
13
   6.0%
Patients with relapse who received ≥ 1 steroid
7
   4.3%
8
   3.7%
Corticosteroids for systemic use
7
   4.3%
8
   3.7%
Methylprednisolone sodium succinate
4
   2.5%
4
   1.8%
Methylprednisolone
3
   1.8%
2
   0.9%
Prednisone
0
   0.0%
3
   1.4%
45.Secondary Outcome
Title Change From Baseline in Patient Determined Disease Steps (PDDS)
Hide Description PDDS scoring ranges 0 to 8. 0 = Normal; 1 = Mild disability; 2 = Moderate disability; 3 = Gait disability; 4 = Early cane; 5 = Late cane; 6 = Bilateral support; 7 = Wheelchair/scooter; 8 = Bedridden.
Time Frame Baseline to Month 12
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Arm/Group Title Cohort 1 Cohort 2
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RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: scores
Baseline (BL) n=163,217 Number Analyzed 163 participants 217 participants
1.7  (1.85) 1.8  (1.90)
Month 12 n=103,188 Number Analyzed 103 participants 188 participants
1.8  (1.95) 1.8  (2.02)
Change from BL to Month 12 n=103,188 Number Analyzed 103 participants 188 participants
-0.1  (0.87) -0.0  (0.78)
46.Secondary Outcome
Title Change From Baseline in T2 Lesion Burden
Hide Description [Not Specified]
Time Frame Baseline to Month 12
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Arm/Group Title Cohort 1 Cohort 2
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RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: number of lesions
Baseline (BL) n=91,84 Number Analyzed 91 participants 84 participants
8.1  (12.74) 9.7  (15.47)
Month 12 n=21,17 Number Analyzed 21 participants 17 participants
6.5  (8.20) 13.1  (13.22)
Change from BL to Month 12 n=21,17 Number Analyzed 21 participants 17 participants
-0.8  (2.36) 3.2  (12.46)
47.Secondary Outcome
Title Change From Baseline for New Gd-Enhancing T1 Lesion Count
Hide Description [Not Specified]
Time Frame Baseline to Month 12
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Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
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RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: number of lesions
Baseline (BL) n=125,147 Number Analyzed 125 participants 147 participants
0.4  (1.09) 0.2  (1.21)
Month 12 n=33,28 Number Analyzed 33 participants 28 participants
0.1  (0.24) 0.2  (0.83)
Change from BL to Month 12 n=33,28 Number Analyzed 33 participants 28 participants
-0.2  (0.61) 0.2  (0.77)
48.Secondary Outcome
Title Change From Baseline to Months 6 and 12 in the Anti-JCV Antibody Index (Index/Value)
Hide Description [Not Specified]
Time Frame Baseline to Month 6 and 12
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Safety analysis set
Arm/Group Title Cohort 1 Cohort 2
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RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day
RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
Overall Number of Participants Analyzed 163 217
Mean (Standard Deviation)
Unit of Measure: cells/uL
Baseline (BL) n=159,215 Number Analyzed 159 participants 215 participants
1.273  (1.2930) 1.391  (1.2600)
Change from BL to Month 6 n=116,195 Number Analyzed 116 participants 195 participants
0.038  (0.2874) 0.045  (0.4724)
Change from BL to Month 12 n=100,180 Number Analyzed 100 participants 180 participants
0.040  (0.3397) 0.145  (0.6062)
Time Frame Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, up to maximum duration of 18. 5 months
Adverse Event Reporting Description Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
 
Arm/Group Title Cohort 1 Cohort 2
Hide Arm/Group Description RMS patients who were newly prescribed commercially available fingolimod 0.5mg per day RMS patients who had been on commercially available fingolimod 0.5mg per day continuously for ≥ 2 years
All-Cause Mortality
Cohort 1 Cohort 2
Affected / at Risk (%) Affected / at Risk (%)
Total   0/163 (0.00%)   0/217 (0.00%) 
Hide Serious Adverse Events
Cohort 1 Cohort 2
Affected / at Risk (%) Affected / at Risk (%)
Total   9/163 (5.52%)   12/217 (5.53%) 
Gastrointestinal disorders     
Abdominal pain † 1  1/163 (0.61%)  0/217 (0.00%) 
Gastric ulcer perforation † 1  0/163 (0.00%)  1/217 (0.46%) 
Nausea † 1  1/163 (0.61%)  0/217 (0.00%) 
Pancreatitis acute † 1  0/163 (0.00%)  1/217 (0.46%) 
Vomiting † 1  1/163 (0.61%)  0/217 (0.00%) 
General disorders     
Asthenia † 1  0/163 (0.00%)  1/217 (0.46%) 
Hyperplasia † 1  1/163 (0.61%)  0/217 (0.00%) 
Non-cardiac chest pain † 1  1/163 (0.61%)  0/217 (0.00%) 
Hepatobiliary disorders     
Cholelithiasis † 1  0/163 (0.00%)  1/217 (0.46%) 
Infections and infestations     
Appendicitis † 1  1/163 (0.61%)  0/217 (0.00%) 
Cellulitis † 1  0/163 (0.00%)  1/217 (0.46%) 
Histoplasmosis disseminated † 1  0/163 (0.00%)  1/217 (0.46%) 
Influenza † 1  1/163 (0.61%)  0/217 (0.00%) 
Pneumonia bacterial † 1  1/163 (0.61%)  0/217 (0.00%) 
Sepsis † 1  0/163 (0.00%)  1/217 (0.46%) 
Staphylococcal infection † 1  0/163 (0.00%)  1/217 (0.46%) 
Urinary tract infection † 1  1/163 (0.61%)  0/217 (0.00%) 
Viral upper respiratory tract infection † 1  0/163 (0.00%)  1/217 (0.46%) 
Injury, poisoning and procedural complications     
Fall † 1  0/163 (0.00%)  1/217 (0.46%) 
Femur fracture † 1  0/163 (0.00%)  1/217 (0.46%) 
Hip fracture † 1  0/163 (0.00%)  1/217 (0.46%) 
Post procedural complication † 1  1/163 (0.61%)  0/217 (0.00%) 
Wrist fracture † 1  1/163 (0.61%)  0/217 (0.00%) 
Metabolism and nutrition disorders     
Dehydration † 1  1/163 (0.61%)  0/217 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain † 1  0/163 (0.00%)  1/217 (0.46%) 
Rhabdomyolysis † 1  0/163 (0.00%)  1/217 (0.46%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma † 1  1/163 (0.61%)  0/217 (0.00%) 
Uterine leiomyoma † 1  1/163 (0.61%)  0/217 (0.00%) 
Nervous system disorders     
Encephalopathy † 1  0/163 (0.00%)  1/217 (0.46%) 
Lumbar radiculopathy † 1  1/163 (0.61%)  0/217 (0.00%) 
Multiple sclerosis relapse † 1  1/163 (0.61%)  0/217 (0.00%) 
Status epilepticus † 1  0/163 (0.00%)  1/217 (0.46%) 
Psychiatric disorders     
Anxiety † 1  1/163 (0.61%)  0/217 (0.00%) 
Reproductive system and breast disorders     
Dysfunctional uterine bleeding † 1  1/163 (0.61%)  0/217 (0.00%) 
1
Term from vocabulary, MedDRA (21.0)
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Cohort 1 Cohort 2
Affected / at Risk (%) Affected / at Risk (%)
Total   70/163 (42.94%)   66/217 (30.41%) 
Blood and lymphatic system disorders     
Leukopenia † 1  3/163 (1.84%)  2/217 (0.92%) 
Lymphopenia † 1  9/163 (5.52%)  1/217 (0.46%) 
Neutropenia † 1  3/163 (1.84%)  3/217 (1.38%) 
Cardiac disorders     
Bradycardia † 1  2/163 (1.23%)  0/217 (0.00%) 
Eye disorders     
Blepharospasm † 1  2/163 (1.23%)  0/217 (0.00%) 
Diplopia † 1  2/163 (1.23%)  0/217 (0.00%) 
Eye pain † 1  2/163 (1.23%)  0/217 (0.00%) 
Macular oedema † 1  2/163 (1.23%)  0/217 (0.00%) 
Photopsia † 1  2/163 (1.23%)  0/217 (0.00%) 
Vision blurred † 1  2/163 (1.23%)  0/217 (0.00%) 
Visual impairment † 1  3/163 (1.84%)  1/217 (0.46%) 
Gastrointestinal disorders     
Abdominal pain upper † 1  2/163 (1.23%)  1/217 (0.46%) 
Nausea † 1  3/163 (1.84%)  2/217 (0.92%) 
Vomiting † 1  2/163 (1.23%)  1/217 (0.46%) 
General disorders     
Chest discomfort † 1  3/163 (1.84%)  0/217 (0.00%) 
Fatigue † 1  8/163 (4.91%)  3/217 (1.38%) 
Gait disturbance † 1  3/163 (1.84%)  3/217 (1.38%) 
Infections and infestations     
Acute sinusitis † 1  2/163 (1.23%)  1/217 (0.46%) 
Pneumonia † 1  2/163 (1.23%)  1/217 (0.46%) 
Sinusitis † 1  2/163 (1.23%)  2/217 (0.92%) 
Upper respiratory tract infection † 1  8/163 (4.91%)  6/217 (2.76%) 
Urinary tract infection † 1  0/163 (0.00%)  7/217 (3.23%) 
Injury, poisoning and procedural complications     
Fall † 1  5/163 (3.07%)  12/217 (5.53%) 
Investigations     
Alanine aminotransferase increased † 1  2/163 (1.23%)  3/217 (1.38%) 
Aspartate aminotransferase increased † 1  2/163 (1.23%)  3/217 (1.38%) 
Lymphocyte count decreased † 1  2/163 (1.23%)  2/217 (0.92%) 
Transaminases increased † 1  2/163 (1.23%)  0/217 (0.00%) 
Metabolism and nutrition disorders     
Vitamin D deficiency † 1  2/163 (1.23%)  0/217 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  5/163 (3.07%)  6/217 (2.76%) 
Back pain † 1  4/163 (2.45%)  4/217 (1.84%) 
Muscle spasms † 1  2/163 (1.23%)  0/217 (0.00%) 
Muscular weakness † 1  3/163 (1.84%)  1/217 (0.46%) 
Pain in extremity † 1  9/163 (5.52%)  3/217 (1.38%) 
Tendonitis † 1  1/163 (0.61%)  3/217 (1.38%) 
Nervous system disorders     
Carpal tunnel syndrome † 1  3/163 (1.84%)  0/217 (0.00%) 
Central nervous system lesion † 1  2/163 (1.23%)  0/217 (0.00%) 
Dizziness † 1  6/163 (3.68%)  1/217 (0.46%) 
Headache † 1  13/163 (7.98%)  4/217 (1.84%) 
Hypoaesthesia † 1  5/163 (3.07%)  1/217 (0.46%) 
Migraine † 1  5/163 (3.07%)  1/217 (0.46%) 
Paraesthesia † 1  3/163 (1.84%)  2/217 (0.92%) 
Tremor † 1  4/163 (2.45%)  0/217 (0.00%) 
Trigeminal neuralgia † 1  2/163 (1.23%)  0/217 (0.00%) 
Psychiatric disorders     
Anxiety † 1  5/163 (3.07%)  3/217 (1.38%) 
Depression † 1  5/163 (3.07%)  2/217 (0.92%) 
Skin and subcutaneous tissue disorders     
Rash † 1  3/163 (1.84%)  2/217 (0.92%) 
Vascular disorders     
Hypertension † 1  4/163 (2.45%)  4/217 (1.84%) 
Hypotension † 1  2/163 (1.23%)  0/217 (0.00%) 
1
Term from vocabulary, MedDRA (21.0)
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: Novartis.email@novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT03257358    
Other Study ID Numbers: CFTY720DUS40
First Submitted: August 18, 2017
First Posted: August 22, 2017
Results First Submitted: June 26, 2020
Results First Posted: July 21, 2020
Last Update Posted: October 7, 2021