Effect of Treatment With Fingolimod on the Immune Response Following Seasonal Flu Vaccination and Tetanus Booster Injection in Patients With Relapsing Multiple Sclerosis (MS)

• Sponsor: Novartis (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01199861
• Collaborator: (none)
• Enrollment: 138
• Locations: 25
• Arms: 2
• Duration (Months): 9
• Patients Per Site: 5.5
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This study will evaluate the effect of treatment with fingolimod on the immune response following seasonal influenza vaccination and tetanus booster injection in patients with relapsing MS.

Condition or Disease	Intervention/Treatment	Phase
Relapsing Multiple Sclerosis	Drug: Fingolimod; Drug: Placebo; Biological: Seasonal influenza vaccine; Biological: Tetanus toxoid vaccine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 138 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 3-month Blinded, Randomized, Multicenter, Placebo-controlled Study to Evaluate the Effect of Treatment With Fingolimod on the Immune Response Following Seasonal Influenza Vaccination and Tetanus Toxoid Booster Injection in Patients With Relapsing Forms of Multiple Sclerosis (MS)
• Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: May 1, 2011
• Actual Study Completion Date: May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fingolimod Participants received Fingolimod 0.5 mg capsules orally once daily for 12 weeks. At Week 6 of study treatment participants received a seasonal influenza vaccination and a tetanus booster vaccination.	Drug: Fingolimod; Fingolimod 0.5 mg capsules for oral administration.; Other Names: FTY720 ; Biological: Seasonal influenza vaccine; Commercially available injectable influenza vaccine for the 2010/11 influenza season.; Other Names: Agrippal (TM) ; Biological: Tetanus toxoid vaccine; Commercially available tetanus toxoid vaccine booster injection.; Other Names: Tetanol (TM)
Placebo Comparator: Placebo Participants received placebo tablets orally once daily for 12 weeks. At Week 6 of study treatment participants received a seasonal influenza vaccination and a tetanus booster vaccination.	Drug: Placebo; Matching placebo capsules for oral administration.; Biological: Seasonal influenza vaccine; Commercially available injectable influenza vaccine for the 2010/11 influenza season.; Other Names: Agrippal (TM) ; Biological: Tetanus toxoid vaccine; Commercially available tetanus toxoid vaccine booster injection.; Other Names: Tetanol (TM)

Outcome Measures

Primary Outcome Measures

1. Immune Response 3 Weeks After Seasonal Influenza Vaccination [Week 6 (pre-vaccination) and 3 weeks after vaccination (Study week 9)]

   Percentage of participants who responded to treatment with the seasonal influenza vaccine 3 weeks after vaccination. Response was defined as patients fulfilling one of the following criteria for at least one of the three strains contained in the seasonal influenza vaccine: Seroconversion: The pre-vaccination antibody titer measurement was <1:10 and the post-vaccination measurement is ≥1:40. Significant increase in antibody titer: The pre-vaccination antibody titer measurement was ≥1:10 and the increase in antibody titer from this to the post-vaccination measurement is ≥ 4-fold.

Secondary Outcome Measures

1. Immune Response 6 Weeks After Seasonal Influenza Vaccination [Week 6 (pre-vaccination) and 6 weeks after vaccination (Study week 12).]

   Percentage of participants who responded to treatment with the seasonal influenza vaccine 6 weeks after vaccination. Response was defined as patients fulfilling one of the following criteria for at least one of the three strains contained in the seasonal influenza vaccine: Seroconversion: The pre-vaccination antibody titer measurement was <1:10 and the post-vaccination measurement is ≥1:40. Significant increase in antibody titer: The pre-vaccination antibody titer measurement was ≥1:10 and the increase in antibody titer from this to the post-vaccination measurement is ≥ 4-fold.

2. Immune Response 3 Weeks After Tetanus Toxoid Booster [Week 6 (pre-vaccination) and 3 weeks after vaccination (Study Week 9)]

   Percentage of participants with an immune response to a single dose of tetanus toxoid three weeks after vaccination. A patient was considered a responder to tetanus toxoid booster vaccination if one of the following criteria was met: Seroconversion: The pre-vaccination antibody titer measurement was <0.1 IU/ml and the post-vaccination measurement was ≥0.4 IU/ml. Significant increase: The pre-vaccination antibody titer measurement was ≥0.1 IU/ml and the increase in antibody titer from this to the post-vaccination measurement was ≥4- fold.

3. Immune Response 6 Weeks After Tetanus Toxoid Booster [Week 6 (pre-vaccination) and 6 weeks after vaccination (Study Week 12)]

   Percentage of participants with an immune response to a single dose of tetanus toxoid six weeks after vaccination. A patient was considered a responder to tetanus toxoid booster vaccination if one of the following criteria was met: Seroconversion: The pre-vaccination antibody titer measurement was <0.1 IU/ml and the post-vaccination measurement was ≥0.4 IU/ml. Significant increase: The pre-vaccination antibody titer measurement was ≥0.1 IU/ml and the increase in antibody titer from this to the post-vaccination measurement was ≥4- fold.

4. Change From Baseline in Seasonal Influenza Vaccine Antibody-titer 3 Weeks After Vaccination [Pre-vaccination (Week 6) and 3 weeks after vaccination (Study Week 9).]

   Change from Baseline was expressed by the ratio of post-vaccination to pre-vaccination antibody titer for each of the three strains included in the seasonal influenza vaccine. Inhibition of an immune response to each strain included in the seasonal influenza vaccine was assessed by the relative difference of the geometric mean antibody titer ratio on fingolimod as compared to placebo three weeks after a single dose of seasonal influenza vaccine.

5. Change From Baseline in Seasonal Influenza Vaccine Antibody-titer 6 Weeks After Vaccination [Pre-vaccination (Week 6) and 6 weeks after vaccination (Study Week 12).]

   Change from Baseline was expressed by the ratio of post-vaccination to pre-vaccination antibody titer for each of the three strains included in the seasonal influenza vaccine. Inhibition of an immune response to each strain included in the seasonal influenza vaccine was assessed by the relative difference of the geometric mean antibody titer ratio on fingolimod as compared to placebo six weeks after a single dose of seasonal influenza vaccine.

6. Number of Participants With Adverse Events (AEs) [From first dose of study drug until 45 days after the last dose of study drug (130 days).]

   Relationship to study drug was determined by the investigator (suspected/not suspected). A serious AE is defined as an event which fulfills one of the following criteria: is fatal or life-threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; requires inpatient hospitalization or prolongation of existing hospitalization; is medically significant, i.e., jeopardizes the patient or may require intervention to prevent one of the outcomes listed above.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Must have relapsing MS

• Must have lifetime tetanus vaccination

• Agree to receive 2010/2011 seasonal influenza vaccine and tetanus toxoid booster injection

Exclusion Criteria:

• Patients with a type of MS that is not relapsing

• Patients with history of chronic immune disease

• Certain cancers

• Diabetic patients with certain eye disorders

• Patients who are on certain immunosuppressive medications or heart medications

• Patients with certain heart conditions

• Patients with certain lung conditions

• Patients who have already received the 2010/2011 seasonal influenza vaccine

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Aalst		Belgium	9300
2	Novartis Investigative Site	Bruxelles		Belgium	1200
3	Novartis Investigative Site	Leuven		Belgium	3000
4	Novartis Investigative Site	Liege		Belgium	4000
5	Novartis Investigative Site	Wilrijk		Belgium	2610
6	Novartis Investigative Site	Nepean	Ontario	Canada	K2G 6E2
7	Novartis Investigative Site	Montreal	Quebec	Canada	H3A 2B4
8	Novartis Investigative Site	Sherbrooke		Canada	JiH 5N4
9	Novartis Investigative Site	Seinajoki		Finland	60220
10	Novartis Investigative Site	Turku		Finland	20100
11	Novartis Investigative Site	Caen		France	14033
12	Novartis Investigative Site	Rennes		France	35043
13	Novartis Investigative Site	St Herblain		France	44800
14	Novartis Investigative Site	Toulouse		France	31059
15	Novartis Investigative Site	Guatemala City		Guatemala	01010
16	Novartis Investigative Site	Guatemala City		Guatemala	01014
17	Novartis Investigative Site	Katowice		Poland	40-594
18	Novartis Investigative Site	Lodz		Poland	90-153
19	Novartis Investigative Site	Madrid		Spain	28029
20	Novartis Investigative Site	Madrid		Spain	28040
21	Novartis Investigative Site	Sevilla		Spain	41009
22	Novartis Investigative Site	Valencia		Spain	46009
23	Novartis Investigational Site	Basel		Switzerland	4031
24	Novartis Investigative Site	Nottingham		United Kingdom	NG7 2UH
25	Novartis Investigative Site	Stoke-on-Trent		United Kingdom	ST4 7LN

Sponsors and Collaborators

• Novartis

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis
• ClinicalTrials.gov Identifier: NCT01199861
• Other Study ID Numbers: CFTY720D2320; 2010-019028-30
• First Posted: Sep 13, 2010
• Last Update Posted: Jun 19, 2012
• Last Verified: May 1, 2012

• Keywords provided by Novartis: Relapsing multiple sclerosis; MS; Immune response
• Additional relevant MeSH terms: Multiple Sclerosis; Sclerosis; Vaccines; Fingolimod Hydrochloride

Study Results

Participant Flow

Pre-assignment Detail	Participants were randomized in a 2:1 ratio to fingolimod 0.5 mg once daily or matching placebo.

Arm/Group Title	Fingolimod	Placebo
Arm/Group Description	Participants received Fingolimod 0.5 mg capsules orally once daily for 12 weeks. At Week 6 of study treatment participants received a seasonal influenza vaccination and a tetanus booster vaccination.	Participants received placebo tablets orally once daily for 12 weeks. At Week 6 of study treatment participants received a seasonal influenza vaccination and a tetanus booster vaccination.
Period Title: Overall Study
STARTED	95	43
COMPLETED	93	43
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	Fingolimod	Placebo	Total
Arm/Group Description	Participants received Fingolimod 0.5 mg capsules orally once daily for 12 weeks. At Week 6 of study treatment participants received a seasonal influenza vaccination and a tetanus booster vaccination.	Participants received placebo tablets orally once daily for 12 weeks. At Week 6 of study treatment participants received a seasonal influenza vaccination and a tetanus booster vaccination.	Total of all reporting groups
Overall Participants	95	43	138
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.4 (8.37)	39.2 (8.67)	37.9 (8.48)
Age, Customized (participants) [Number]
18-30	25 26.3%	8 18.6%	33 23.9%
31-40	35 36.8%	14 32.6%	49 35.5%
41-55	35 36.8%	21 48.8%	56 40.6%
Sex: Female, Male (Count of Participants)
Female	65 68.4%	29 67.4%	94 68.1%
Male	30 31.6%	14 32.6%	44 31.9%

Outcome Measures

1. Primary Outcome

Title	Immune Response 3 Weeks After Seasonal Influenza Vaccination
Description	Percentage of participants who responded to treatment with the seasonal influenza vaccine 3 weeks after vaccination. Response was defined as patients fulfilling one of the following criteria for at least one of the three strains contained in the seasonal influenza vaccine: Seroconversion: The pre-vaccination antibody titer measurement was <1:10 and the post-vaccination measurement is ≥1:40. Significant increase in antibody titer: The pre-vaccination antibody titer measurement was ≥1:10 and the increase in antibody titer from this to the post-vaccination measurement is ≥ 4-fold.
Time Frame	Week 6 (pre-vaccination) and 3 weeks after vaccination (Study week 9)

Outcome Measure Data

Analysis Population Description

The full analysis set which includes all patients who were randomized and received at least 1 dose of study drug, and for whom data were available.

Arm/Group Title	Fingolimod	Placebo
Arm/Group Description	Participants received Fingolimod 0.5 mg capsules orally once daily for 12 weeks. At Week 6 of study treatment participants received a seasonal influenza vaccination and a tetanus booster vaccination.	Participants received placebo tablets orally once daily for 12 weeks. At Week 6 of study treatment participants received a seasonal influenza vaccination and a tetanus booster vaccination.
Measure Participants	90	43
Number [percentage of participants]	53.3 56.1%	83.7 194.7%

2. Secondary Outcome

Title	Immune Response 6 Weeks After Seasonal Influenza Vaccination
Description	Percentage of participants who responded to treatment with the seasonal influenza vaccine 6 weeks after vaccination. Response was defined as patients fulfilling one of the following criteria for at least one of the three strains contained in the seasonal influenza vaccine: Seroconversion: The pre-vaccination antibody titer measurement was <1:10 and the post-vaccination measurement is ≥1:40. Significant increase in antibody titer: The pre-vaccination antibody titer measurement was ≥1:10 and the increase in antibody titer from this to the post-vaccination measurement is ≥ 4-fold.
Time Frame	Week 6 (pre-vaccination) and 6 weeks after vaccination (Study week 12).

Outcome Measure Data

Analysis Population Description

Full analysis set for whom data were available.

Arm/Group Title	Fingolimod	Placebo
Arm/Group Description	Participants received Fingolimod 0.5 mg capsules orally once daily for 12 weeks. At Week 6 of study treatment participants received a seasonal influenza vaccination and a tetanus booster vaccination.	Participants received placebo tablets orally once daily for 12 weeks. At Week 6 of study treatment participants received a seasonal influenza vaccination and a tetanus booster vaccination.
Measure Participants	88	43
Number [percentage of participants]	43.2 45.5%	74.4 173%

3. Secondary Outcome

Title	Immune Response 3 Weeks After Tetanus Toxoid Booster
Description	Percentage of participants with an immune response to a single dose of tetanus toxoid three weeks after vaccination. A patient was considered a responder to tetanus toxoid booster vaccination if one of the following criteria was met: Seroconversion: The pre-vaccination antibody titer measurement was <0.1 IU/ml and the post-vaccination measurement was ≥0.4 IU/ml. Significant increase: The pre-vaccination antibody titer measurement was ≥0.1 IU/ml and the increase in antibody titer from this to the post-vaccination measurement was ≥4- fold.
Time Frame	Week 6 (pre-vaccination) and 3 weeks after vaccination (Study Week 9)

Outcome Measure Data

Analysis Population Description

Full analysis set for whom data were available.

Arm/Group Title	Fingolimod	Placebo
Arm/Group Description	Participants received Fingolimod 0.5 mg capsules orally once daily for 12 weeks. At Week 6 of study treatment participants received a seasonal influenza vaccination and a tetanus booster vaccination.	Participants received placebo tablets orally once daily for 12 weeks. At Week 6 of study treatment participants received a seasonal influenza vaccination and a tetanus booster vaccination.
Measure Participants	90	43
Number [percentage of participants]	40.0 42.1%	60.5 140.7%

4. Secondary Outcome

Title	Immune Response 6 Weeks After Tetanus Toxoid Booster
Description	Percentage of participants with an immune response to a single dose of tetanus toxoid six weeks after vaccination. A patient was considered a responder to tetanus toxoid booster vaccination if one of the following criteria was met: Seroconversion: The pre-vaccination antibody titer measurement was <0.1 IU/ml and the post-vaccination measurement was ≥0.4 IU/ml. Significant increase: The pre-vaccination antibody titer measurement was ≥0.1 IU/ml and the increase in antibody titer from this to the post-vaccination measurement was ≥4- fold.
Time Frame	Week 6 (pre-vaccination) and 6 weeks after vaccination (Study Week 12)

Outcome Measure Data

Analysis Population Description

Full analysis set for whom data were available.

Arm/Group Title	Fingolimod	Placebo
Arm/Group Description	Participants received Fingolimod 0.5 mg capsules orally once daily for 12 weeks. At Week 6 of study treatment participants received a seasonal influenza vaccination and a tetanus booster vaccination.	Participants received placebo tablets orally once daily for 12 weeks. At Week 6 of study treatment participants received a seasonal influenza vaccination and a tetanus booster vaccination.
Measure Participants	88	43
Number [percentage of participants]	37.5 39.5%	48.8 113.5%

5. Secondary Outcome

Title	Change From Baseline in Seasonal Influenza Vaccine Antibody-titer 3 Weeks After Vaccination
Description	Change from Baseline was expressed by the ratio of post-vaccination to pre-vaccination antibody titer for each of the three strains included in the seasonal influenza vaccine. Inhibition of an immune response to each strain included in the seasonal influenza vaccine was assessed by the relative difference of the geometric mean antibody titer ratio on fingolimod as compared to placebo three weeks after a single dose of seasonal influenza vaccine.
Time Frame	Pre-vaccination (Week 6) and 3 weeks after vaccination (Study Week 9).

Outcome Measure Data

Analysis Population Description

Full analysis set for whom data were available.

Arm/Group Title	Fingolimod	Placebo
Arm/Group Description	Participants received Fingolimod 0.5 mg capsules orally once daily for 12 weeks. At Week 6 of study treatment participants received a seasonal influenza vaccination and a tetanus booster vaccination.	Participants received placebo tablets orally once daily for 12 weeks. At Week 6 of study treatment participants received a seasonal influenza vaccination and a tetanus booster vaccination.
Measure Participants	90	43
A/California/7/09(H1N1)	2.45	4.14
A/Perth/16/2009(H3N2)	0.49	0.36
B/Brisbane/60/2008	1.34	2.40

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fingolimod, Placebo
	Comments	The inhibition of an immune response to the A/California/7/09 (H1N1) strain of the seasonal influenza vaccine was assessed by the relative difference of the geometric mean antibody titer ratio on fingolimod as compared to placebo three weeks after a single dose of seasonal influenza vaccine.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percent Inhibition
	Estimated Value	41.0
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	One minus the back-transformed estimate for the treatment difference was interpreted as the relative inhibition of an immune response caused by fingolimod 0.5 mg compared to placebo; it was presented as a percentage and referred to as 'inhibition'.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Fingolimod, Placebo
	Comments	The inhibition of an immune response to the A/Perth/16/2009 (H3N2) strain of the seasonal influenza vaccine was assessed by the relative difference of the geometric mean antibody titer ratio on fingolimod as compared to placebo three weeks after a single dose of seasonal influenza vaccine.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percent Inhibition
	Estimated Value	-35.0
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	One minus the back-transformed estimate for the treatment difference was interpreted as the relative inhibition of an immune response caused by fingolimod 0.5 mg compared to placebo; it was presented as a percentage and referred to as 'inhibition'.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Fingolimod, Placebo
	Comments	The inhibition of an immune response to the B/Brisbane/60/2008 strain of the seasonal influenza vaccine was assessed by the relative difference of the geometric mean antibody titer ratio on fingolimod as compared to placebo three weeks after a single dose of seasonal influenza vaccine.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percent Inhibition
	Estimated Value	44.0
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	One minus the back-transformed estimate for the treatment difference was interpreted as the relative inhibition of an immune response caused by fingolimod 0.5 mg compared to placebo; it was presented as a percentage and referred to as 'inhibition'.

6. Secondary Outcome

Title	Change From Baseline in Seasonal Influenza Vaccine Antibody-titer 6 Weeks After Vaccination
Description	Change from Baseline was expressed by the ratio of post-vaccination to pre-vaccination antibody titer for each of the three strains included in the seasonal influenza vaccine. Inhibition of an immune response to each strain included in the seasonal influenza vaccine was assessed by the relative difference of the geometric mean antibody titer ratio on fingolimod as compared to placebo six weeks after a single dose of seasonal influenza vaccine.
Time Frame	Pre-vaccination (Week 6) and 6 weeks after vaccination (Study Week 12).

Outcome Measure Data

Analysis Population Description

Full analysis set for whom data were available.

Arm/Group Title	Fingolimod	Placebo
Arm/Group Description	Participants received Fingolimod 0.5 mg capsules orally once daily for 12 weeks. At Week 6 of study treatment participants received a seasonal influenza vaccination and a tetanus booster vaccination.	Participants received placebo tablets orally once daily for 12 weeks. At Week 6 of study treatment participants received a seasonal influenza vaccination and a tetanus booster vaccination.
Measure Participants	88	43
A/California/7/09(H1N1)	1.81	2.91
A/Perth/16/2009(H3N2)	0.36	0.28
B/Brisbane/60/2008	1.08	2.07

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fingolimod, Placebo
	Comments	The inhibition of an immune response to the A/California/7/09 (H1N1) strain of the seasonal influenza vaccine was assessed by the relative difference of the geometric mean antibody titer ratio on fingolimod as compared to placebo six weeks after a single dose of seasonal influenza vaccine.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percent Inhibition
	Estimated Value	38.0
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	One minus the back-transformed estimate for the treatment difference was interpreted as the relative inhibition of an immune response caused by fingolimod 0.5 mg compared to placebo; it was presented as a percentage and referred to as 'inhibition'.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Fingolimod, Placebo
	Comments	The inhibition of an immune response to the A/Perth/16/2009 (H3N2) strain of the seasonal influenza vaccine was assessed by the relative difference of the geometric mean antibody titer ratio on fingolimod as compared to placebo six weeks after a single dose of seasonal influenza vaccine.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percent Inhibition
	Estimated Value	-28.0
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	One minus the back-transformed estimate for the treatment difference was interpreted as the relative inhibition of an immune response caused by fingolimod 0.5 mg compared to placebo; it was presented as a percentage and referred to as 'inhibition'.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Fingolimod, Placebo
	Comments	The inhibition of an immune response to the B/Brisbane/60/2008 strain of the seasonal influenza vaccine was assessed by the relative difference of the geometric mean antibody titer ratio on fingolimod as compared to placebo six weeks after a single dose of seasonal influenza vaccine.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percent Inhibition
	Estimated Value	48.0
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	One minus the back-transformed estimate for the treatment difference was interpreted as the relative inhibition of an immune response caused by fingolimod 0.5 mg compared to placebo; it was presented as a percentage and referred to as 'inhibition'.

7. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	Relationship to study drug was determined by the investigator (suspected/not suspected). A serious AE is defined as an event which fulfills one of the following criteria: is fatal or life-threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; requires inpatient hospitalization or prolongation of existing hospitalization; is medically significant, i.e., jeopardizes the patient or may require intervention to prevent one of the outcomes listed above.
Time Frame	From first dose of study drug until 45 days after the last dose of study drug (130 days).

Outcome Measure Data

Analysis Population Description

Safety set - all patients who received at least 1 dose of study drug.

Arm/Group Title	Fingolimod	Placebo
Arm/Group Description	Participants received Fingolimod 0.5 mg capsules orally once daily for 12 weeks. At Week 6 of study treatment participants received a seasonal influenza vaccination and a tetanus booster vaccination.	Participants received placebo tablets orally once daily for 12 weeks. At Week 6 of study treatment participants received a seasonal influenza vaccination and a tetanus booster vaccination.
Measure Participants	95	43
Any adverse event	82 86.3%	34 79.1%
AE related to study drug	42 44.2%	11 25.6%
Serious adverse event	1 1.1%	2 4.7%
Adverse events leading to discontinuation	1 1.1%	0 0%

Adverse Events

Arm/Group Title	Fingolimod		Placebo
Arm/Group Description	Participants received Fingolimod 0.5 mg capsules orally once daily for 12 weeks. At Week 6 of study treatment participants received a seasonal influenza vaccination and a tetanus booster vaccination.		Participants received placebo tablets orally once daily for 12 weeks. At Week 6 of study treatment participants received a seasonal influenza vaccination and a tetanus booster vaccination.
All Cause Mortality
	Fingolimod		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Fingolimod		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/95 (1.1%)		2/43 (4.7%)
Infections and infestations
Herpes zoster	0/95 (0%)		1/43 (2.3%)
Injury, poisoning and procedural complications
Hip fracture	0/95 (0%)		1/43 (2.3%)
Nervous system disorders
Paraparesis	1/95 (1.1%)		0/43 (0%)
Other (Not Including Serious) Adverse Events
	Fingolimod		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	51/95 (53.7%)		22/43 (51.2%)
Blood and lymphatic system disorders
Lymphopenia	10/95 (10.5%)		0/43 (0%)
Gastrointestinal disorders
Diarrhoea	3/95 (3.2%)		3/43 (7%)
Nausea	2/95 (2.1%)		4/43 (9.3%)
General disorders
Fatigue	3/95 (3.2%)		3/43 (7%)
Infections and infestations
Nasopharyngitis	15/95 (15.8%)		8/43 (18.6%)
Upper respiratory tract infection	11/95 (11.6%)		6/43 (14%)
Urinary tract infection	5/95 (5.3%)		2/43 (4.7%)
Nervous system disorders
Headache	18/95 (18.9%)		4/43 (9.3%)
Respiratory, thoracic and mediastinal disorders
Cough	7/95 (7.4%)		0/43 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.