Trial Outcomes & Findings for Effect of Treatment With Fingolimod on the Immune Response Following Seasonal Flu Vaccination and Tetanus Booster Injection in Patients With Relapsing Multiple Sclerosis (MS) (NCT NCT01199861)
NCT ID: NCT01199861
Last Updated: 2012-06-19
Results Overview
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.
COMPLETED
PHASE3
138 participants
Week 6 (pre-vaccination) and 3 weeks after vaccination (Study week 9)
2012-06-19
Participant Flow
Participants were randomized in a 2:1 ratio to fingolimod 0.5 mg once daily or matching placebo.
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
95
|
43
|
|
Overall Study
COMPLETED
|
93
|
43
|
|
Overall Study
NOT COMPLETED
|
2
|
0
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
Administrative problems
|
1
|
0
|
|
Overall Study
Adverse Event
|
1
|
0
|
Baseline Characteristics
Effect of Treatment With Fingolimod on the Immune Response Following Seasonal Flu Vaccination and Tetanus Booster Injection in Patients With Relapsing Multiple Sclerosis (MS)
Baseline characteristics by cohort
| Measure |
Fingolimod
n=95 Participants
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.
|
Placebo
n=43 Participants
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
n=138 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
37.4 years
STANDARD_DEVIATION 8.37 • n=5 Participants
|
39.2 years
STANDARD_DEVIATION 8.67 • n=7 Participants
|
37.9 years
STANDARD_DEVIATION 8.48 • n=5 Participants
|
|
Age, Customized
18-30
|
25 participants
n=5 Participants
|
8 participants
n=7 Participants
|
33 participants
n=5 Participants
|
|
Age, Customized
31-40
|
35 participants
n=5 Participants
|
14 participants
n=7 Participants
|
49 participants
n=5 Participants
|
|
Age, Customized
41-55
|
35 participants
n=5 Participants
|
21 participants
n=7 Participants
|
56 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
65 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
94 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
30 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
44 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 6 (pre-vaccination) and 3 weeks after vaccination (Study week 9)Population: 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.
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.
Outcome measures
| Measure |
Fingolimod
n=90 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|
|
Immune Response 3 Weeks After Seasonal Influenza Vaccination
|
53.3 percentage of participants
|
83.7 percentage of participants
|
SECONDARY outcome
Timeframe: Week 6 (pre-vaccination) and 6 weeks after vaccination (Study week 12).Population: Full analysis set for whom data were available.
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.
Outcome measures
| Measure |
Fingolimod
n=88 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|
|
Immune Response 6 Weeks After Seasonal Influenza Vaccination
|
43.2 percentage of participants
|
74.4 percentage of participants
|
SECONDARY outcome
Timeframe: Week 6 (pre-vaccination) and 3 weeks after vaccination (Study Week 9)Population: Full analysis set for whom data were available.
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: 1. Seroconversion: The pre-vaccination antibody titer measurement was \<0.1 IU/ml and the post-vaccination measurement was ≥0.4 IU/ml. 2. 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.
Outcome measures
| Measure |
Fingolimod
n=90 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|
|
Immune Response 3 Weeks After Tetanus Toxoid Booster
|
40.0 percentage of participants
|
60.5 percentage of participants
|
SECONDARY outcome
Timeframe: Week 6 (pre-vaccination) and 6 weeks after vaccination (Study Week 12)Population: Full analysis set for whom data were available.
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: 1. Seroconversion: The pre-vaccination antibody titer measurement was \<0.1 IU/ml and the post-vaccination measurement was ≥0.4 IU/ml. 2. 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.
Outcome measures
| Measure |
Fingolimod
n=88 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|
|
Immune Response 6 Weeks After Tetanus Toxoid Booster
|
37.5 percentage of participants
|
48.8 percentage of participants
|
SECONDARY outcome
Timeframe: Pre-vaccination (Week 6) and 3 weeks after vaccination (Study Week 9).Population: Full analysis set for whom data were available.
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.
Outcome measures
| Measure |
Fingolimod
n=90 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|
|
Change From Baseline in Seasonal Influenza Vaccine Antibody-titer 3 Weeks After Vaccination
A/California/7/09(H1N1)
|
2.45 ratio
|
4.14 ratio
|
|
Change From Baseline in Seasonal Influenza Vaccine Antibody-titer 3 Weeks After Vaccination
A/Perth/16/2009(H3N2)
|
0.49 ratio
|
0.36 ratio
|
|
Change From Baseline in Seasonal Influenza Vaccine Antibody-titer 3 Weeks After Vaccination
B/Brisbane/60/2008
|
1.34 ratio
|
2.40 ratio
|
SECONDARY outcome
Timeframe: Pre-vaccination (Week 6) and 6 weeks after vaccination (Study Week 12).Population: Full analysis set for whom data were available.
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.
Outcome measures
| Measure |
Fingolimod
n=88 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|
|
Change From Baseline in Seasonal Influenza Vaccine Antibody-titer 6 Weeks After Vaccination
A/California/7/09(H1N1)
|
1.81 ratio
|
2.91 ratio
|
|
Change From Baseline in Seasonal Influenza Vaccine Antibody-titer 6 Weeks After Vaccination
A/Perth/16/2009(H3N2)
|
0.36 ratio
|
0.28 ratio
|
|
Change From Baseline in Seasonal Influenza Vaccine Antibody-titer 6 Weeks After Vaccination
B/Brisbane/60/2008
|
1.08 ratio
|
2.07 ratio
|
SECONDARY outcome
Timeframe: From first dose of study drug until 45 days after the last dose of study drug (130 days).Population: Safety set - all patients who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
Fingolimod
n=95 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|
|
Number of Participants With Adverse Events (AEs)
Any adverse event
|
82 participants
|
34 participants
|
|
Number of Participants With Adverse Events (AEs)
AE related to study drug
|
42 participants
|
11 participants
|
|
Number of Participants With Adverse Events (AEs)
Serious adverse event
|
1 participants
|
2 participants
|
|
Number of Participants With Adverse Events (AEs)
Adverse events leading to discontinuation
|
1 participants
|
0 participants
|
Adverse Events
Fingolimod
Placebo
Serious adverse events
| Measure |
Fingolimod
n=95 participants at risk
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.
|
Placebo
n=43 participants at risk
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.
|
|---|---|---|
|
Infections and infestations
Herpes zoster
|
0.00%
0/95
|
2.3%
1/43
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.00%
0/95
|
2.3%
1/43
|
|
Nervous system disorders
Paraparesis
|
1.1%
1/95
|
0.00%
0/43
|
Other adverse events
| Measure |
Fingolimod
n=95 participants at risk
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.
|
Placebo
n=43 participants at risk
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.
|
|---|---|---|
|
Blood and lymphatic system disorders
Lymphopenia
|
10.5%
10/95
|
0.00%
0/43
|
|
Gastrointestinal disorders
Diarrhoea
|
3.2%
3/95
|
7.0%
3/43
|
|
Gastrointestinal disorders
Nausea
|
2.1%
2/95
|
9.3%
4/43
|
|
General disorders
Fatigue
|
3.2%
3/95
|
7.0%
3/43
|
|
Infections and infestations
Nasopharyngitis
|
15.8%
15/95
|
18.6%
8/43
|
|
Infections and infestations
Upper respiratory tract infection
|
11.6%
11/95
|
14.0%
6/43
|
|
Infections and infestations
Urinary tract infection
|
5.3%
5/95
|
4.7%
2/43
|
|
Nervous system disorders
Headache
|
18.9%
18/95
|
9.3%
4/43
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.4%
7/95
|
0.00%
0/43
|
Additional Information
Study Director
Novartis Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER