Trial Outcomes & Findings for Study to Investigate the Immune Response to Influenza Vaccine in Patients With Multiple Sclerosis on Teriflunomide (NCT NCT01403376)
NCT ID: NCT01403376
Last Updated: 2016-02-18
Results Overview
For each viral strain (H1N1, H3N2, and B), the antibody titer, level of antibodies in blood sample when exposed to antigen, was calculated as the mean of two replicates. If the titer was below or above the limit of detection, the threshold value was used. The percentage of participants achieving a titer of 40 or more, as well as the 90% confidence interval (CI) using normal approximation were calculated for each strain and treatment group.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
128 participants
Primary outcome timeframe
28 days post vaccination
Results posted on
2016-02-18
Participant Flow
The recruitment initiated in September 2011 was completed in December 2011. A total of 137 patients were screened at 14 sites in 5 countries. Participants treated with teriflunomide were recruited in the LTS6048-NCT00228163 study and in the LTS6050-NCT00803049 study.
In order to ensure at least 40 participants were enrolled in the teriflunomide 14 mg group while maintaining the blind in the study LTS6050 an interactive voice response system (IVRS) was set up to include participants from both studies LTS6048 and LTS6050 into this study. 128 participants were enrolled and vaccinated at 14 sites.
Participant milestones
| Measure |
Teriflunomide 7 mg
Influenza vaccine in participants treated with teriflunomide 7 mg for at least 6 months
|
Teriflunomide 14 mg
Influenza vaccine in participants treated with teriflunomide 14 mg for at least 6 months
|
IFN-β-1
Influenza vaccine in participants treated with a stable dose of interferon-β-1 (IFN-β-1) for at least 6 months
|
|---|---|---|---|
|
Overall Study
STARTED
|
41
|
41
|
46
|
|
Overall Study
COMPLETED
|
41
|
41
|
46
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study to Investigate the Immune Response to Influenza Vaccine in Patients With Multiple Sclerosis on Teriflunomide
Baseline characteristics by cohort
| Measure |
Teriflunomide 7 mg
n=41 Participants
Influenza vaccine in participants treated with teriflunomide 7 mg for at least 6 months
|
Teriflunomide 14 mg
n=41 Participants
Influenza vaccine in participants treated with teriflunomide 14 mg for at least 6 months
|
IFN-β-1
n=46 Participants
Influenza vaccine in participants treated with a stable dose of interferon-β-1 (IFN-β-1) for at least 6 months
|
Total
n=128 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
46.1 years
STANDARD_DEVIATION 7.9 • n=5 Participants
|
43.8 years
STANDARD_DEVIATION 8.5 • n=7 Participants
|
45.1 years
STANDARD_DEVIATION 10.8 • n=5 Participants
|
45.0 years
STANDARD_DEVIATION 9.2 • n=4 Participants
|
|
Sex: Female, Male
Female
|
28 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
89 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
39 Participants
n=4 Participants
|
|
pre-vaccination antibody titer - H1N1 strain
<10
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
0 participants
n=5 Participants
|
1 participants
n=4 Participants
|
|
pre-vaccination antibody titer - H1N1 strain
Between 10 and 40 (<)
|
7 participants
n=5 Participants
|
4 participants
n=7 Participants
|
5 participants
n=5 Participants
|
16 participants
n=4 Participants
|
|
pre-vaccination antibody titer - H1N1 strain
≥40
|
34 participants
n=5 Participants
|
36 participants
n=7 Participants
|
41 participants
n=5 Participants
|
111 participants
n=4 Participants
|
|
pre-vaccination antibody titer - H3N2 strain
<10
|
2 participants
n=5 Participants
|
3 participants
n=7 Participants
|
2 participants
n=5 Participants
|
7 participants
n=4 Participants
|
|
pre-vaccination antibody titer - H3N2 strain
Between 10 and 40 (<)
|
16 participants
n=5 Participants
|
15 participants
n=7 Participants
|
22 participants
n=5 Participants
|
53 participants
n=4 Participants
|
|
pre-vaccination antibody titer - H3N2 strain
≥40
|
23 participants
n=5 Participants
|
23 participants
n=7 Participants
|
22 participants
n=5 Participants
|
68 participants
n=4 Participants
|
|
pre-vaccination antibody titer - B strain
<10
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
|
pre-vaccination antibody titer - B strain
Between 10 and 40 (<)
|
12 participants
n=5 Participants
|
13 participants
n=7 Participants
|
21 participants
n=5 Participants
|
46 participants
n=4 Participants
|
|
pre-vaccination antibody titer - B strain
≥40
|
29 participants
n=5 Participants
|
28 participants
n=7 Participants
|
25 participants
n=5 Participants
|
82 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 28 days post vaccinationPopulation: Per-protocol population: Enrolled and vaccinated participants with antibody assessments at Day 28, but excluding those with important events/deviations potentially impacting analysis (multiple sclerosis relapse, poor compliance to treatment, interfering concomitant drug). Participants were considered according to the treatment actually received.
For each viral strain (H1N1, H3N2, and B), the antibody titer, level of antibodies in blood sample when exposed to antigen, was calculated as the mean of two replicates. If the titer was below or above the limit of detection, the threshold value was used. The percentage of participants achieving a titer of 40 or more, as well as the 90% confidence interval (CI) using normal approximation were calculated for each strain and treatment group.
Outcome measures
| Measure |
Teriflunomide 7 mg
n=40 Participants
Influenza vaccine in participants treated with teriflunomide 7 mg for at least 6 months
|
Teriflunomide 14 mg
n=39 Participants
Influenza vaccine in participants treated with teriflunomide 14 mg for at least 6 months
|
IFN-β-1
n=43 Participants
Influenza vaccine in participants treated with a stable dose of interferon-β-1 (IFN-β-1) for at least 6 months
|
|---|---|---|---|
|
Percentage of Participants With Antibody Titer ≥40 at 28 Days Post Vaccination
H1N1 strain
|
97.5 percentage of participants
Interval 93.4 to 100.0
|
97.4 percentage of participants
Interval 93.3 to 100.0
|
97.7 percentage of participants
Interval 93.9 to 100.0
|
|
Percentage of Participants With Antibody Titer ≥40 at 28 Days Post Vaccination
H3N2 strain
|
90.0 percentage of participants
Interval 82.2 to 97.8
|
76.9 percentage of participants
Interval 65.8 to 88.0
|
90.7 percentage of participants
Interval 83.4 to 98.0
|
|
Percentage of Participants With Antibody Titer ≥40 at 28 Days Post Vaccination
B strain
|
97.5 percentage of participants
Interval 93.4 to 100.0
|
97.4 percentage of participants
Interval 93.3 to 100.0
|
93.0 percentage of participants
Interval 86.6 to 99.4
|
SECONDARY outcome
Timeframe: pre vaccination (baseline) and 28 days post vaccinationPopulation: Per-protocol population as previously defined
Percentages of participants with an increase from baseline of 2-fold or more in antibody titers and 90% CIs using normal approximation were calculated for each strain and treatment group.
Outcome measures
| Measure |
Teriflunomide 7 mg
n=40 Participants
Influenza vaccine in participants treated with teriflunomide 7 mg for at least 6 months
|
Teriflunomide 14 mg
n=39 Participants
Influenza vaccine in participants treated with teriflunomide 14 mg for at least 6 months
|
IFN-β-1
n=43 Participants
Influenza vaccine in participants treated with a stable dose of interferon-β-1 (IFN-β-1) for at least 6 months
|
|---|---|---|---|
|
Percentage of Participants With 2 Fold or More Increase in Antibody Titer at 28 Days Post Vaccination
H3N2 strain
|
35.0 percentage of participants
Interval 22.6 to 47.4
|
41.0 percentage of participants
Interval 28.1 to 54.0
|
51.2 percentage of participants
Interval 38.6 to 63.7
|
|
Percentage of Participants With 2 Fold or More Increase in Antibody Titer at 28 Days Post Vaccination
B strain
|
47.5 percentage of participants
Interval 34.5 to 60.5
|
51.3 percentage of participants
Interval 38.1 to 64.4
|
58.1 percentage of participants
Interval 45.8 to 70.5
|
|
Percentage of Participants With 2 Fold or More Increase in Antibody Titer at 28 Days Post Vaccination
H1N1 strain
|
35.0 percentage of participants
Interval 22.6 to 47.4
|
30.8 percentage of participants
Interval 18.6 to 42.9
|
46.5 percentage of participants
Interval 34.0 to 59.0
|
SECONDARY outcome
Timeframe: pre vaccination (baseline) and 28 days post vaccinationPopulation: Per-protocol population as previously defined
Percentages of participants with an increase from baseline of 4-fold or more in antibody titers and 90% CIs using normal approximation were calculated for each strain and treatment group.
Outcome measures
| Measure |
Teriflunomide 7 mg
n=40 Participants
Influenza vaccine in participants treated with teriflunomide 7 mg for at least 6 months
|
Teriflunomide 14 mg
n=39 Participants
Influenza vaccine in participants treated with teriflunomide 14 mg for at least 6 months
|
IFN-β-1
n=43 Participants
Influenza vaccine in participants treated with a stable dose of interferon-β-1 (IFN-β-1) for at least 6 months
|
|---|---|---|---|
|
Percentage of Participants With 4 Fold or More Increase in Antibody Titer at 28 Days Post Vaccination
H3N2 strain
|
25.0 percentage of participants
Interval 13.7 to 36.3
|
23.1 percentage of participants
Interval 12.0 to 34.2
|
41.9 percentage of participants
Interval 29.5 to 54.2
|
|
Percentage of Participants With 4 Fold or More Increase in Antibody Titer at 28 Days Post Vaccination
H1N1 strain
|
22.5 percentage of participants
Interval 11.6 to 33.4
|
20.5 percentage of participants
Interval 9.9 to 31.1
|
39.5 percentage of participants
Interval 27.3 to 51.8
|
|
Percentage of Participants With 4 Fold or More Increase in Antibody Titer at 28 Days Post Vaccination
B strain
|
37.5 percentage of participants
Interval 24.9 to 50.1
|
30.8 percentage of participants
Interval 18.6 to 42.9
|
51.2 percentage of participants
Interval 38.6 to 63.7
|
SECONDARY outcome
Timeframe: pre vaccination (baseline) and 28 days post vaccinationPopulation: Per-protocol population as previously defined
Outcome measures
| Measure |
Teriflunomide 7 mg
n=40 Participants
Influenza vaccine in participants treated with teriflunomide 7 mg for at least 6 months
|
Teriflunomide 14 mg
n=39 Participants
Influenza vaccine in participants treated with teriflunomide 14 mg for at least 6 months
|
IFN-β-1
n=43 Participants
Influenza vaccine in participants treated with a stable dose of interferon-β-1 (IFN-β-1) for at least 6 months
|
|---|---|---|---|
|
Geometric Mean of Titers (GMT) Ratio Post/Pre Vaccination
H1N1 strain
|
2.5 ratio post/pre vaccination
Interval 2.0 to 3.3
|
2.3 ratio post/pre vaccination
Interval 1.9 to 2.9
|
3.4 ratio post/pre vaccination
Interval 2.6 to 4.5
|
|
Geometric Mean of Titers (GMT) Ratio Post/Pre Vaccination
H3N2 strain
|
2.6 ratio post/pre vaccination
Interval 1.9 to 3.5
|
2.6 ratio post/pre vaccination
Interval 1.9 to 3.6
|
4.1 ratio post/pre vaccination
Interval 3.0 to 5.4
|
|
Geometric Mean of Titers (GMT) Ratio Post/Pre Vaccination
B strain
|
3.1 ratio post/pre vaccination
Interval 2.3 to 4.2
|
3.0 ratio post/pre vaccination
Interval 2.3 to 3.9
|
4.7 ratio post/pre vaccination
Interval 3.6 to 6.2
|
SECONDARY outcome
Timeframe: pre vaccination (baseline) and 28 days post vaccinationPopulation: Per-protocol population as previously defined
Outcome measures
| Measure |
Teriflunomide 7 mg
n=40 Participants
Influenza vaccine in participants treated with teriflunomide 7 mg for at least 6 months
|
Teriflunomide 14 mg
n=39 Participants
Influenza vaccine in participants treated with teriflunomide 14 mg for at least 6 months
|
IFN-β-1
n=43 Participants
Influenza vaccine in participants treated with a stable dose of interferon-β-1 (IFN-β-1) for at least 6 months
|
|---|---|---|---|
|
Immunoglobulin Levels
Immunoglobulin M - pre vaccination
|
1.28 g/L
Standard Deviation 0.57
|
1.23 g/L
Standard Deviation 0.59
|
1.14 g/L
Standard Deviation 0.58
|
|
Immunoglobulin Levels
Immunoglobulin M - 28-day post vaccination
|
1.30 g/L
Standard Deviation 0.56
|
1.27 g/L
Standard Deviation 0.60
|
1.16 g/L
Standard Deviation 0.54
|
|
Immunoglobulin Levels
Immunoglobulin G - pre vaccination
|
9.35 g/L
Standard Deviation 1.82
|
9.12 g/L
Standard Deviation 2.24
|
12.03 g/L
Standard Deviation 3.01
|
|
Immunoglobulin Levels
Immunoglobulin G - 28-day post vaccination
|
9.57 g/L
Standard Deviation 2.08
|
9.09 g/L
Standard Deviation 2.25
|
12.25 g/L
Standard Deviation 2.69
|
|
Immunoglobulin Levels
Immunoglobulin A - pre vaccination
|
1.65 g/L
Standard Deviation 0.66
|
1.51 g/L
Standard Deviation 0.64
|
2.27 g/L
Standard Deviation 1.07
|
|
Immunoglobulin Levels
Immunoglobulin A - 28-day post vaccination
|
1.63 g/L
Standard Deviation 0.68
|
1.50 g/L
Standard Deviation 0.63
|
2.33 g/L
Standard Deviation 1.07
|
Adverse Events
Teriflunomide 7mg
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Teriflunomide 14mg
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
IFN-β-1
Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Teriflunomide 7mg
n=41 participants at risk
Influenza vaccine in participants treated with teriflunomide 7 mg for at least 6 months
|
Teriflunomide 14mg
n=41 participants at risk
Influenza vaccine in participants treated with teriflunomide 14 mg for at least 6 months
|
IFN-β-1
n=46 participants at risk
Influenza vaccine in participants treated with a stable dose of interferon-β-1 (IFN-β-1) for at least 6 months
|
|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
4.9%
2/41 • Adverse events (AE) were collected from signature of the Informed Consent Form (ICF) up to the last visit in the study.
The analysis was performed on the included and vaccinated population and included all AE that developed or worsened from vaccination up to the end of study visit at Day 28.
|
7.3%
3/41 • Adverse events (AE) were collected from signature of the Informed Consent Form (ICF) up to the last visit in the study.
The analysis was performed on the included and vaccinated population and included all AE that developed or worsened from vaccination up to the end of study visit at Day 28.
|
13.0%
6/46 • Adverse events (AE) were collected from signature of the Informed Consent Form (ICF) up to the last visit in the study.
The analysis was performed on the included and vaccinated population and included all AE that developed or worsened from vaccination up to the end of study visit at Day 28.
|
|
Nervous system disorders
Headache
|
2.4%
1/41 • Adverse events (AE) were collected from signature of the Informed Consent Form (ICF) up to the last visit in the study.
The analysis was performed on the included and vaccinated population and included all AE that developed or worsened from vaccination up to the end of study visit at Day 28.
|
2.4%
1/41 • Adverse events (AE) were collected from signature of the Informed Consent Form (ICF) up to the last visit in the study.
The analysis was performed on the included and vaccinated population and included all AE that developed or worsened from vaccination up to the end of study visit at Day 28.
|
6.5%
3/46 • Adverse events (AE) were collected from signature of the Informed Consent Form (ICF) up to the last visit in the study.
The analysis was performed on the included and vaccinated population and included all AE that developed or worsened from vaccination up to the end of study visit at Day 28.
|
|
General disorders
Influenza like illness
|
0.00%
0/41 • Adverse events (AE) were collected from signature of the Informed Consent Form (ICF) up to the last visit in the study.
The analysis was performed on the included and vaccinated population and included all AE that developed or worsened from vaccination up to the end of study visit at Day 28.
|
2.4%
1/41 • Adverse events (AE) were collected from signature of the Informed Consent Form (ICF) up to the last visit in the study.
The analysis was performed on the included and vaccinated population and included all AE that developed or worsened from vaccination up to the end of study visit at Day 28.
|
8.7%
4/46 • Adverse events (AE) were collected from signature of the Informed Consent Form (ICF) up to the last visit in the study.
The analysis was performed on the included and vaccinated population and included all AE that developed or worsened from vaccination up to the end of study visit at Day 28.
|
|
General disorders
Injection site pain
|
2.4%
1/41 • Adverse events (AE) were collected from signature of the Informed Consent Form (ICF) up to the last visit in the study.
The analysis was performed on the included and vaccinated population and included all AE that developed or worsened from vaccination up to the end of study visit at Day 28.
|
2.4%
1/41 • Adverse events (AE) were collected from signature of the Informed Consent Form (ICF) up to the last visit in the study.
The analysis was performed on the included and vaccinated population and included all AE that developed or worsened from vaccination up to the end of study visit at Day 28.
|
6.5%
3/46 • Adverse events (AE) were collected from signature of the Informed Consent Form (ICF) up to the last visit in the study.
The analysis was performed on the included and vaccinated population and included all AE that developed or worsened from vaccination up to the end of study visit at Day 28.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee If no publication has occurred within 12 months after trial completion, the Investigator can present or publish results. The Investigator provides the Sponsor with a copy of the presentation or publication for review and comment at least 30 days in advance of its submission. The Sponsor can delay the submission for a period not exceeding 90 days to allow for filing a patent application or such other measures as the Sponsor deems appropriate to establish and preserve its proprietary rights.
- Publication restrictions are in place
Restriction type: OTHER