Trial Outcomes & Findings for A Phase I/II Trial of Tetravalent Live Attenuated Dengue Vaccine in Flavivirus Antibody Naive Infants (NCT NCT00322049)
NCT ID: NCT00322049
Last Updated: 2018-01-19
Results Overview
Local and general solicited reactogenicity using diary cards for 21 days (days 0-20) after the first dose of dengue/control vaccine
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
51 participants
Primary outcome timeframe
21-day follow-up period after Dose 1
Results posted on
2018-01-19
Participant Flow
51 infants enrolled and vaccinated for safety cohort, all received dose 1 and 50 completed the study. 49 vaccinated for ATP immunogenicity cohort.
Participant milestones
| Measure |
Cohort A - 1/10th Dose Dengue Vaccine
1/10th full dose at study months 0 and 6 or control vaccines (varicells vaccine at study month 0 and Hib vaccine at study month 6)
|
Cohort B - Full Dose Dengue Vaccine
Full-dose of dengue vaccine at study months 0 and 6 or control vaccines (varicells vaccine at study month 0 and Hib vaccine at study month 6)
|
Cohort C - Full Dose Dengue Vaccine
Full-dose dengue vaccine at study months 0 and 6 or control vaccines (varicells vaccine at study month 0 and Hib vaccine at study month 6)
|
Control Group - Hib Vaccine
Hemophilus influenza type b (Hib) vaccine and varicella vaccine
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
4
|
10
|
20
|
17
|
|
Overall Study
COMPLETED
|
4
|
9
|
20
|
16
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
1
|
Reasons for withdrawal
| Measure |
Cohort A - 1/10th Dose Dengue Vaccine
1/10th full dose at study months 0 and 6 or control vaccines (varicells vaccine at study month 0 and Hib vaccine at study month 6)
|
Cohort B - Full Dose Dengue Vaccine
Full-dose of dengue vaccine at study months 0 and 6 or control vaccines (varicells vaccine at study month 0 and Hib vaccine at study month 6)
|
Cohort C - Full Dose Dengue Vaccine
Full-dose dengue vaccine at study months 0 and 6 or control vaccines (varicells vaccine at study month 0 and Hib vaccine at study month 6)
|
Control Group - Hib Vaccine
Hemophilus influenza type b (Hib) vaccine and varicella vaccine
|
|---|---|---|---|---|
|
Overall Study
Moved out of area
|
0
|
0
|
0
|
1
|
|
Overall Study
Infected with Dengue during study
|
0
|
1
|
0
|
0
|
Baseline Characteristics
A Phase I/II Trial of Tetravalent Live Attenuated Dengue Vaccine in Flavivirus Antibody Naive Infants
Baseline characteristics by cohort
| Measure |
Cohort A - 1/10th Dose Dengue Vaccine
n=4 Participants
1/10th full dose at study months 0 and 6 or control vaccines (varicells vaccine at study month 0 and Hib vaccine at study month 6)
|
Cohort B - Full Dose Dengue Vaccine
n=10 Participants
Full-dose of dengue vaccine at study months 0 and 6 or control vaccines (varicells vaccine at study month 0 and Hib vaccine at study month 6)
|
Cohort C - Full Dose Dengue Vaccine
n=20 Participants
Full-dose dengue vaccine at study months 0 and 6 or control vaccines (varicells vaccine at study month 0 and Hib vaccine at study month 6)
|
Control Group - Hib Vaccine
n=17 Participants
Hemophilus influenza type b (Hib) vaccine and varicella vaccine
|
Total
n=51 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
14.0 months
STANDARD_DEVIATION 0.00 • n=5 Participants
|
13.3 months
STANDARD_DEVIATION 0.82 • n=7 Participants
|
13.6 months
STANDARD_DEVIATION 0.88 • n=5 Participants
|
13.6 months
STANDARD_DEVIATION 0.79 • n=4 Participants
|
13.6 months
STANDARD_DEVIATION 0.80 • n=21 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
23 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
28 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Southeast Asian
|
4 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
17 Participants
n=4 Participants
|
51 Participants
n=21 Participants
|
|
Region of Enrollment
Thailand
|
4 participants
n=5 Participants
|
10 participants
n=7 Participants
|
20 participants
n=5 Participants
|
17 participants
n=4 Participants
|
51 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 21-day follow-up period after Dose 1Population: Format of results is consistent with how data was presented in the Final Clinical Study Report. Combining of cohorts B and C was due to both cohorts being full dose
Local and general solicited reactogenicity using diary cards for 21 days (days 0-20) after the first dose of dengue/control vaccine
Outcome measures
| Measure |
Control Group - Hib Vaccine
n=17 Participants
Hemophilus influenza type b (Hib) vaccine and varicella vaccine
|
Cohort A - 1/10th Dose Dengue Vaccine
n=4 Participants
1/10th full dose at study months 0 and 6 or control vaccines (varicells vaccine at study month 0 and Hib vaccine at study month 6)
|
Cohorts B & C - Full Dose Dengue Vaccine
n=30 Participants
Full-dose of dengue vaccine at study months 0 and 6 or control vaccines (varicells vaccine at study month 0 and Hib vaccine at study month 6)
|
Cohorts B & C - Full Dose Dengue Vaccine
Full dose dengue vaccine at study months 0 and 6
|
Cohorts B & C - Full Dose Dengue Vaccine
Full dose dengue vaccine at study months 0 and 6
|
|---|---|---|---|---|---|
|
Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine.
Overall / dose - Loss of appetite
|
13 specified events
|
2 specified events
|
21 specified events
|
—
|
—
|
|
Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine.
Overall / dose - Fever (axillary celsius)
|
16 specified events
|
3 specified events
|
24 specified events
|
—
|
—
|
|
Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine.
Dose 2 : Redness
|
3 specified events
|
1 specified events
|
13 specified events
|
—
|
—
|
|
Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine.
Dose 2 : Swelling
|
1 specified events
|
1 specified events
|
8 specified events
|
—
|
—
|
|
Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine.
Overall / dose : Redness
|
4 specified events
|
3 specified events
|
34 specified events
|
—
|
—
|
|
Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine.
Overall / dose - Vomiting
|
12 specified events
|
2 specified events
|
24 specified events
|
—
|
—
|
|
Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine.
Dose 1 : Pain
|
3 specified events
|
1 specified events
|
11 specified events
|
—
|
—
|
|
Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine.
Dose 1 : Redness
|
1 specified events
|
2 specified events
|
21 specified events
|
—
|
—
|
|
Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine.
Dose 1 : Swelling
|
2 specified events
|
1 specified events
|
16 specified events
|
—
|
—
|
|
Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine.
Dose 2 : Pain
|
2 specified events
|
1 specified events
|
13 specified events
|
—
|
—
|
|
Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine.
Overall / dose : Pain
|
5 specified events
|
2 specified events
|
24 specified events
|
—
|
—
|
|
Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine.
Overall / dose : Swelling
|
3 specified events
|
2 specified events
|
24 specified events
|
—
|
—
|
|
Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine.
Overall / subject : Pain
|
3 specified events
|
1 specified events
|
18 specified events
|
—
|
—
|
|
Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine.
Overall / subject : Redness
|
3 specified events
|
2 specified events
|
22 specified events
|
—
|
—
|
|
Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine.
Overall / subject : Swelling
|
2 specified events
|
1 specified events
|
19 specified events
|
—
|
—
|
|
Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine.
Overall / dose - Cough
|
15 specified events
|
4 specified events
|
27 specified events
|
—
|
—
|
|
Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine.
Overall / dose - Decreased activity
|
11 specified events
|
2 specified events
|
11 specified events
|
—
|
—
|
|
Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine.
Overall / dose - Drowsiness
|
12 specified events
|
0 specified events
|
18 specified events
|
—
|
—
|
|
Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine.
Overall / dose - Irritability
|
13 specified events
|
3 specified events
|
23 specified events
|
—
|
—
|
PRIMARY outcome
Timeframe: 30 days post Dose 2Population: GMT calculated on all subjects. Dil = Dilution; P1(M1) = blood sampling on month after dose 1, at study month 1; PII(M7) = blood sampling one month after dose 2, at study month 7; PII(M8.5) = blood sampling 2 1/2 months after dose 2, at study month 8.5. Combining of cohorts B and C was due to both cohorts being full dose
Assess the immunogenicity of the dengue vaccine in terms of GMTs 30 days post-Dose 2 of dengue vaccine for all four serotypes (DEN-1, 2, 3, 4 and JE (Japanese encephalitis)). Analysis of immunogenicity was performed on the ATP cohort.
Outcome measures
| Measure |
Control Group - Hib Vaccine
n=17 Participants
Hemophilus influenza type b (Hib) vaccine and varicella vaccine
|
Cohort A - 1/10th Dose Dengue Vaccine
n=4 Participants
1/10th full dose at study months 0 and 6 or control vaccines (varicells vaccine at study month 0 and Hib vaccine at study month 6)
|
Cohorts B & C - Full Dose Dengue Vaccine
n=30 Participants
Full-dose of dengue vaccine at study months 0 and 6 or control vaccines (varicells vaccine at study month 0 and Hib vaccine at study month 6)
|
Cohorts B & C - Full Dose Dengue Vaccine
Full dose dengue vaccine at study months 0 and 6
|
Cohorts B & C - Full Dose Dengue Vaccine
Full dose dengue vaccine at study months 0 and 6
|
|---|---|---|---|---|---|
|
Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine
DEN-1 GMT - PII(M7)
|
5.0 titers
Interval 5.0 to 5.0
|
6.1 titers
Interval 3.3 to 11.4
|
20.7 titers
Interval 11.4 to 37.7
|
—
|
—
|
|
Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine
DEN-2 GMT - PI(M1)
|
5.0 titers
Interval 5.0 to 5.0
|
8.8 titers
Interval 1.4 to 54.4
|
13.7 titers
Interval 7.7 to 24.5
|
—
|
—
|
|
Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine
DEN-2 GMT - PII(M7)
|
5.0 titers
Interval 5.0 to 5.0
|
173.6 titers
Interval 50.1 to 601.5
|
239.6 titers
Interval 163.6 to 351.1
|
—
|
—
|
|
Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine
DEN-3 GMT - PI(M1)
|
5.0 titers
Interval 5.0 to 5.0
|
5.0 titers
Interval 5.0 to 5.0
|
5.0 titers
Interval 5.0 to 5.0
|
—
|
—
|
|
Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine
DEN-3 GMT PII(M7)
|
5.0 titers
Interval 5.0 to 5.0
|
5.0 titers
Interval 5.0 to 5.0
|
29.2 titers
Interval 18.6 to 45.7
|
—
|
—
|
|
Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine
DEN-4 GMT PI(M1)
|
5.0 titers
Interval 5.0 to 5.0
|
15.7 titers
Interval 0.4 to 600.1
|
22.5 titers
Interval 10.0 to 50.3
|
—
|
—
|
|
Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine
DEN-4 GMT PII(M7)
|
5.0 titers
Interval 5.0 to 5.0
|
31.9 titers
Interval 2.5 to 408.2
|
52.5 titers
Interval 29.0 to 95.0
|
—
|
—
|
|
Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine
JE Vaccine GMT PI(M1)
|
5.0 titers
Interval 5.0 to 5.0
|
5.0 titers
Interval 5.0 to 5.0
|
6.0 titers
Interval 5.0 to 7.2
|
—
|
—
|
|
Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine
JE Vaccine GMT PII(M7)
|
5.0 titers
Interval 5.0 to 5.0
|
5.0 titers
Interval 5.0 to 5.0
|
8.3 titers
Interval 5.1 to 13.6
|
—
|
—
|
|
Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine
JE Vaccine GMT PII(M8.5)
|
16.8 titers
Interval 7.4 to 38.1
|
19.3 titers
Interval 7.0 to 52.9
|
12.9 titers
Interval 6.7 to 24.6
|
—
|
—
|
|
Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine
DEN-1 GMT - PI(M1)
|
5.0 titers
Interval 5.0 to 5.0
|
5.0 titers
Interval 5.0 to 5.0
|
5.2 titers
Interval 4.8 to 5.5
|
—
|
—
|
PRIMARY outcome
Timeframe: month 7 after dose 2Seronegative for N antibody against DEN 1, 2, 3 and 4 antibody after dengue dose 2. Seronegative (antibody titer \<10 1/Dil for N lg to DEN-1, N lg to DEN-2, N lg to DEN-3, N lg) prior to vaccination.
Outcome measures
| Measure |
Control Group - Hib Vaccine
n=4 Participants
Hemophilus influenza type b (Hib) vaccine and varicella vaccine
|
Cohort A - 1/10th Dose Dengue Vaccine
n=9 Participants
1/10th full dose at study months 0 and 6 or control vaccines (varicells vaccine at study month 0 and Hib vaccine at study month 6)
|
Cohorts B & C - Full Dose Dengue Vaccine
n=20 Participants
Full-dose of dengue vaccine at study months 0 and 6 or control vaccines (varicells vaccine at study month 0 and Hib vaccine at study month 6)
|
Cohorts B & C - Full Dose Dengue Vaccine
n=29 Participants
Full dose dengue vaccine at study months 0 and 6
|
Cohorts B & C - Full Dose Dengue Vaccine
Full dose dengue vaccine at study months 0 and 6
|
|---|---|---|---|---|---|
|
Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dose 2
N lg to DEN-1 (Dil)
|
25.0 % of responders
Interval 0.6 to 80.6
|
88.9 % of responders
Interval 51.8 to 99.7
|
40.0 % of responders
Interval 19.1 to 63.9
|
55.2 % of responders
Interval 35.7 to 73.6
|
—
|
|
Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dose 2
N lg to DEN-3 (Dil)
|
0.0 % of responders
Interval 0.0 to 0.0
|
100 % of responders
Interval 66.4 to 100.0
|
80.0 % of responders
Interval 56.3 to 94.3
|
86.2 % of responders
Interval 68.3 to 96.1
|
—
|
|
Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dose 2
N lg to DEN-4 (Dil)
|
75.0 % of responders
Interval 19.4 to 99.4
|
100 % of responders
Interval 66.4 to 100.0
|
94.7 % of responders
Interval 74.0 to 99.9
|
96.4 % of responders
Interval 81.7 to 99.9
|
—
|
|
Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dose 2
N lg to DEN-2 (Dil)
|
100 % of responders
Interval 39.8 to 100.0
|
100 % of responders
Interval 66.4 to 100.0
|
100 % of responders
Interval 82.4 to 100.0
|
100 % of responders
Interval 87.7 to 100.0
|
—
|
PRIMARY outcome
Timeframe: month 8.5Seropositivity for N antibody against DEN 1, 2, 3 and 4 antibody after dengue dose 2 (and 2 doses of JE). Seronegative (antibody titer \<10 1/Dil for N lg to DEN-1, N lg to DEN-2, N lg to DEN-3, N lg) prior to vaccination.
Outcome measures
| Measure |
Control Group - Hib Vaccine
n=4 Participants
Hemophilus influenza type b (Hib) vaccine and varicella vaccine
|
Cohort A - 1/10th Dose Dengue Vaccine
n=9 Participants
1/10th full dose at study months 0 and 6 or control vaccines (varicells vaccine at study month 0 and Hib vaccine at study month 6)
|
Cohorts B & C - Full Dose Dengue Vaccine
n=20 Participants
Full-dose of dengue vaccine at study months 0 and 6 or control vaccines (varicells vaccine at study month 0 and Hib vaccine at study month 6)
|
Cohorts B & C - Full Dose Dengue Vaccine
n=29 Participants
Full dose dengue vaccine at study months 0 and 6
|
Cohorts B & C - Full Dose Dengue Vaccine
Full dose dengue vaccine at study months 0 and 6
|
|---|---|---|---|---|---|
|
Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dengue Dose 2 (and 2 Doses of JE
N lg to DEN-1 (Dil)
|
25.0 % of responders
Interval 0.6 to 80.6
|
55.6 % of responders
Interval 21.2 to 86.3
|
35.0 % of responders
Interval 15.4 to 59.2
|
41.4 % of responders
Interval 23.5 to 61.1
|
—
|
|
Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dengue Dose 2 (and 2 Doses of JE
N lg to DEN-2 (Dil)
|
100 % of responders
Interval 39.8 to 100.0
|
100 % of responders
Interval 66.4 to 100.0
|
100 % of responders
Interval 82.4 to 100.0
|
100 % of responders
Interval 87.7 to 100.0
|
—
|
|
Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dengue Dose 2 (and 2 Doses of JE
N lg to DEN-3 (Dil)
|
25.0 % of responders
Interval 0.6 to 80.6
|
77.8 % of responders
Interval 40.0 to 97.2
|
60.0 % of responders
Interval 36.1 to 80.9
|
65.5 % of responders
Interval 45.7 to 82.1
|
—
|
|
Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dengue Dose 2 (and 2 Doses of JE
N lg to DEN-4 (Dil)
|
50.0 % of responders
Interval 6.8 to 93.2
|
88.9 % of responders
Interval 51.8 to 99.7
|
60.0 % of responders
Interval 36.1 to 80.9
|
69.0 % of responders
Interval 49.2 to 84.7
|
—
|
PRIMARY outcome
Timeframe: Pre-vaccination, 1, 6, 7 and 8.5 months after two doses of dengue vaccinePopulation: Combining of cohorts B and C was due to both cohorts being full dose
Seropositivity rates and GMTs for N lg to JEV antibodies. Pre= Pre vaccination, blood sampling prior to the first vaccine dose; PI(M1)= Post 1, month 1, blood sampling one month after dose 1 at study month 1; PI(M6)= Post 1, month 6, blood sampling 6 months after dose 1 at study month 6; PII(M7)= Post II, month 7, blood sampling one month after dose 2 at study month 7; PIV(M8.5)= Post IV, month 8.5, blood sampling after 2 doses of dengue/control and 2 doses of JE vaccines at study month 8.5
Outcome measures
| Measure |
Control Group - Hib Vaccine
n=16 Participants
Hemophilus influenza type b (Hib) vaccine and varicella vaccine
|
Cohort A - 1/10th Dose Dengue Vaccine
n=4 Participants
1/10th full dose at study months 0 and 6 or control vaccines (varicells vaccine at study month 0 and Hib vaccine at study month 6)
|
Cohorts B & C - Full Dose Dengue Vaccine
n=29 Participants
Full-dose of dengue vaccine at study months 0 and 6 or control vaccines (varicells vaccine at study month 0 and Hib vaccine at study month 6)
|
Cohorts B & C - Full Dose Dengue Vaccine
Full dose dengue vaccine at study months 0 and 6
|
Cohorts B & C - Full Dose Dengue Vaccine
Full dose dengue vaccine at study months 0 and 6
|
|---|---|---|---|---|---|
|
JE Vaccine Response
GMT - PII(M7)
|
5.0 % of subjects with titer within range
Interval 5.0 to 5.0
|
5.0 % of subjects with titer within range
Interval 5.0 to 5.0
|
8.3 % of subjects with titer within range
Interval 5.1 to 13.6
|
—
|
—
|
|
JE Vaccine Response
GMT - PRE
|
5.0 % of subjects with titer within range
Interval 5.0 to 5.0
|
5.0 % of subjects with titer within range
Interval 5.0 to 5.0
|
5.0 % of subjects with titer within range
Interval 5.0 to 5.0
|
—
|
—
|
|
JE Vaccine Response
N lg against JEV >10 1/Dil - PI(M1)
|
0.0 % of subjects with titer within range
Interval 0.0 to 20.6
|
0.0 % of subjects with titer within range
Interval 0.0 to 60.2
|
13.8 % of subjects with titer within range
Interval 3.9 to 31.7
|
—
|
—
|
|
JE Vaccine Response
GMT - PI(M1)
|
5.0 % of subjects with titer within range
Interval 5.0 to 5.0
|
5.0 % of subjects with titer within range
Interval 5.0 to 5.0
|
6.0 % of subjects with titer within range
Interval 5.0 to 7.2
|
—
|
—
|
|
JE Vaccine Response
N lg against JEV >10 1/Dil - PRE
|
0.0 % of subjects with titer within range
Interval 0.0 to 20.6
|
0.0 % of subjects with titer within range
Interval 0.0 to 60.2
|
0.0 % of subjects with titer within range
Interval 0.0 to 11.9
|
—
|
—
|
|
JE Vaccine Response
N lg against JEV >10 1/Dil - PI(M6)
|
6.3 % of subjects with titer within range
Interval 0.2 to 30.2
|
0.0 % of subjects with titer within range
Interval 0.0 to 60.2
|
0.0 % of subjects with titer within range
Interval 0.0 to 11.9
|
—
|
—
|
|
JE Vaccine Response
GMT - PI(M6)
|
5.3 % of subjects with titer within range
Interval 4.7 to 5.9
|
5.0 % of subjects with titer within range
Interval 5.0 to 5.0
|
5.0 % of subjects with titer within range
Interval 5.0 to 5.0
|
—
|
—
|
|
JE Vaccine Response
N lg against JEV >10 1/Dil - PII(M7)
|
0.0 % of subjects with titer within range
Interval 0.0 to 20.6
|
0.0 % of subjects with titer within range
Interval 0.0 to 60.2
|
17.9 % of subjects with titer within range
Interval 6.1 to 36.9
|
—
|
—
|
|
JE Vaccine Response
N lg against JEV >10 1/Dil - PIV(M8.5)
|
56.3 % of subjects with titer within range
Interval 29.9 to 80.2
|
100 % of subjects with titer within range
Interval 39.8 to 100.0
|
32.1 % of subjects with titer within range
Interval 15.9 to 52.4
|
—
|
—
|
|
JE Vaccine Response
GMT - PIV(M8.5)
|
16.8 % of subjects with titer within range
Interval 7.4 to 38.1
|
19.3 % of subjects with titer within range
Interval 7.0 to 52.9
|
12.9 % of subjects with titer within range
Interval 6.7 to 24.6
|
—
|
—
|
SECONDARY outcome
Timeframe: 30-day follow-up period after dose 1 and 2Percentage of subjects showing incidence of dengue specific symptoms during the 30-day follow-up period after vaccinations
Outcome measures
| Measure |
Control Group - Hib Vaccine
n=17 Participants
Hemophilus influenza type b (Hib) vaccine and varicella vaccine
|
Cohort A - 1/10th Dose Dengue Vaccine
n=4 Participants
1/10th full dose at study months 0 and 6 or control vaccines (varicells vaccine at study month 0 and Hib vaccine at study month 6)
|
Cohorts B & C - Full Dose Dengue Vaccine
n=10 Participants
Full-dose of dengue vaccine at study months 0 and 6 or control vaccines (varicells vaccine at study month 0 and Hib vaccine at study month 6)
|
Cohorts B & C - Full Dose Dengue Vaccine
n=20 Participants
Full dose dengue vaccine at study months 0 and 6
|
Cohorts B & C - Full Dose Dengue Vaccine
n=30 Participants
Full dose dengue vaccine at study months 0 and 6
|
|---|---|---|---|---|---|
|
Incidence of Dengue Specific Symptoms
Dose 2 - Hepatomegaly
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 19.51
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 60.24
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 30.85
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 16.84
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 11.57
|
|
Incidence of Dengue Specific Symptoms
Dose 2 - Spenomegaly
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 19.51
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 60.24
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 30.85
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 16.84
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 11.57
|
|
Incidence of Dengue Specific Symptoms
Dose 1 - Rash
|
5.9 % of subjects with specified symptoms
Interval 0.15 to 28.69
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 60.24
|
30.0 % of subjects with specified symptoms
Interval 6.67 to 65.25
|
15.0 % of subjects with specified symptoms
Interval 3.21 to 37.89
|
20.0 % of subjects with specified symptoms
Interval 7.71 to 38.57
|
|
Incidence of Dengue Specific Symptoms
Dose 1 - Hemorrhage
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 19.51
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 60.24
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 30.85
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 16.84
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 11.57
|
|
Incidence of Dengue Specific Symptoms
Dose 1 - Conjunctival hemorrhage
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 19.51
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 60.24
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 30.85
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 16.84
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 11.57
|
|
Incidence of Dengue Specific Symptoms
Dose 1 - Conjunctival injection
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 19.51
|
0.00 % of subjects with specified symptoms
Interval 0.0 to 60.24
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 30.85
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 16.84
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 11.57
|
|
Incidence of Dengue Specific Symptoms
Dose 1 - Mucosal hemorrhage
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 19.51
|
25.0 % of subjects with specified symptoms
Interval 0.63 to 80.59
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 30.85
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 16.84
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 11.57
|
|
Incidence of Dengue Specific Symptoms
Dose 1 - Lymphadenopathy
|
70.6 % of subjects with specified symptoms
Interval 44.04 to 89.69
|
50.0 % of subjects with specified symptoms
Interval 6.76 to 93.24
|
80.0 % of subjects with specified symptoms
Interval 44.39 to 97.48
|
50.0 % of subjects with specified symptoms
Interval 27.2 to 72.8
|
60.0 % of subjects with specified symptoms
Interval 40.6 to 77.34
|
|
Incidence of Dengue Specific Symptoms
Dose 1 - Hepatomegaly
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 19.51
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 60.24
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 30.85
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 16.84
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 11.57
|
|
Incidence of Dengue Specific Symptoms
Dose 1 - Splenomegaly
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 19.51
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 60.24
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 30.85
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 16.84
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 11.57
|
|
Incidence of Dengue Specific Symptoms
Dose 2 - Rash
|
11.8 % of subjects with specified symptoms
Interval 1.46 to 36.44
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 60.24
|
10.0 % of subjects with specified symptoms
Interval 0.25 to 44.5
|
5.0 % of subjects with specified symptoms
Interval 0.13 to 24.87
|
6.7 % of subjects with specified symptoms
Interval 0.82 to 22.07
|
|
Incidence of Dengue Specific Symptoms
Dose 2 - Hemorrhage
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 19.51
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 60.24
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 30.85
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 16.84
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 11.57
|
|
Incidence of Dengue Specific Symptoms
Dose 2 - Conjunctival hemorrhage
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 19.51
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 60.24
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 30.85
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 16.54
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 11.57
|
|
Incidence of Dengue Specific Symptoms
Dose 2 - Conjunctival injecgtion
|
5.9 % of subjects with specified symptoms
Interval 0.15 to 28.69
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 60.24
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 30.85
|
15.0 % of subjects with specified symptoms
Interval 3.21 to 37.89
|
10.0 % of subjects with specified symptoms
Interval 2.11 to 26.53
|
|
Incidence of Dengue Specific Symptoms
Dose 2 - Mucosal hemorrhage
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 19.51
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 60.24
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 30.85
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 16.84
|
0.0 % of subjects with specified symptoms
Interval 0.0 to 11.57
|
|
Incidence of Dengue Specific Symptoms
Dose 2 - Lymphadenopathy
|
58.8 % of subjects with specified symptoms
Interval 32.92 to 81.56
|
75.0 % of subjects with specified symptoms
Interval 19.41 to 99.37
|
60.0 % of subjects with specified symptoms
Interval 26.24 to 87.84
|
25.0 % of subjects with specified symptoms
Interval 8.66 to 49.1
|
36.7 % of subjects with specified symptoms
Interval 19.93 to 56.14
|
SECONDARY outcome
Timeframe: 10 days after post dose 1 and 2Population: All participants with evaluable results are reported via RT-PCR and Nested PCR analysis. Scheduled phlebotomy and unscheduled phlebotomy when a subject was ill during the study revealed dengue viremia by RT-/nested PCR, for seven subjects (2 in cohort B and 5 in cohort C).
Percentage of subjects with a dengue viremia 10 days after each dose of vaccine. RT PCR = Reverse-transcriptase polymerase chain reaction Nested PCR - Nested polymerase chain reaction Per protocol, all participants receiving a Dengue Vaccine were combined for Dengue Viremia assessment via RT-PCR and Nested PCR
Outcome measures
| Measure |
Control Group - Hib Vaccine
n=34 Participants
Hemophilus influenza type b (Hib) vaccine and varicella vaccine
|
Cohort A - 1/10th Dose Dengue Vaccine
n=34 Participants
1/10th full dose at study months 0 and 6 or control vaccines (varicells vaccine at study month 0 and Hib vaccine at study month 6)
|
Cohorts B & C - Full Dose Dengue Vaccine
Full-dose of dengue vaccine at study months 0 and 6 or control vaccines (varicells vaccine at study month 0 and Hib vaccine at study month 6)
|
Cohorts B & C - Full Dose Dengue Vaccine
Full dose dengue vaccine at study months 0 and 6
|
Cohorts B & C - Full Dose Dengue Vaccine
Full dose dengue vaccine at study months 0 and 6
|
|---|---|---|---|---|---|
|
Percentage of Subjects With a Dengue Viremia 10 Days Post Booster Dose
10 days post dose 2
|
0.0 % of subjects
|
5.9 % of subjects
|
—
|
—
|
—
|
|
Percentage of Subjects With a Dengue Viremia 10 Days Post Booster Dose
10 days post dose 1
|
2.9 % of subjects
|
14.7 % of subjects
|
—
|
—
|
—
|
Adverse Events
Cohort A: Dengue Vaccine- 1/10 Dose (T-DEN F17 )
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Cohort B: Full Dose (T-DEN F17 )
Serious events: 1 serious events
Other events: 10 other events
Deaths: 0 deaths
Cohort C: Dengue Vaccine - Full Dose (T-DEN F17 )
Serious events: 0 serious events
Other events: 20 other events
Deaths: 0 deaths
Control Group
Serious events: 3 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Cohort A: Dengue Vaccine- 1/10 Dose (T-DEN F17 )
n=4 participants at risk
Dengue vaccine at Months 0 and 6 and booster follow-up at 3 years;
|
Cohort B: Full Dose (T-DEN F17 )
n=10 participants at risk
Control vaccines: Hemophilus influenza type b (Hib) vaccine and varicella vaccine
|
Cohort C: Dengue Vaccine - Full Dose (T-DEN F17 )
n=20 participants at risk
Dengue vaccine at Months 0 and 6 and booster follow-up at 3 years
|
Control Group
n=17 participants at risk
Hemophilus influenza type b (Hib) vaccine and varicella vaccine
|
|---|---|---|---|---|
|
Injury, poisoning and procedural complications
Fracture left forearm
|
0.00%
0/4 • 8.5 months
|
10.0%
1/10 • Number of events 1 • 8.5 months
|
0.00%
0/20 • 8.5 months
|
0.00%
0/17 • 8.5 months
|
|
Gastrointestinal disorders
Acute gastroenteritis with dehydration
|
0.00%
0/4 • 8.5 months
|
0.00%
0/10 • 8.5 months
|
0.00%
0/20 • 8.5 months
|
5.9%
1/17 • Number of events 1 • 8.5 months
|
|
Gastrointestinal disorders
Acute gastroenteritis with febrile seizure
|
0.00%
0/4 • 8.5 months
|
0.00%
0/10 • 8.5 months
|
0.00%
0/20 • 8.5 months
|
5.9%
1/17 • Number of events 1 • 8.5 months
|
|
Gastrointestinal disorders
Viral gastritis with dehydration/vomiting, fever
|
0.00%
0/4 • 8.5 months
|
0.00%
0/10 • 8.5 months
|
0.00%
0/20 • 8.5 months
|
5.9%
1/17 • Number of events 1 • 8.5 months
|
Other adverse events
| Measure |
Cohort A: Dengue Vaccine- 1/10 Dose (T-DEN F17 )
n=4 participants at risk
Dengue vaccine at Months 0 and 6 and booster follow-up at 3 years;
|
Cohort B: Full Dose (T-DEN F17 )
n=10 participants at risk
Control vaccines: Hemophilus influenza type b (Hib) vaccine and varicella vaccine
|
Cohort C: Dengue Vaccine - Full Dose (T-DEN F17 )
n=20 participants at risk
Dengue vaccine at Months 0 and 6 and booster follow-up at 3 years
|
Control Group
n=17 participants at risk
Hemophilus influenza type b (Hib) vaccine and varicella vaccine
|
|---|---|---|---|---|
|
General disorders
Pain
|
25.0%
1/4 • Number of events 1 • 8.5 months
|
20.0%
2/10 • Number of events 2 • 8.5 months
|
55.0%
11/20 • Number of events 11 • 8.5 months
|
11.8%
2/17 • Number of events 2 • 8.5 months
|
|
Skin and subcutaneous tissue disorders
Redness
|
25.0%
1/4 • Number of events 1 • 8.5 months
|
10.0%
1/10 • Number of events 1 • 8.5 months
|
60.0%
12/20 • Number of events 12 • 8.5 months
|
17.6%
3/17 • Number of events 3 • 8.5 months
|
|
General disorders
Swelling
|
25.0%
1/4 • Number of events 1 • 8.5 months
|
0.00%
0/10 • 8.5 months
|
40.0%
8/20 • Number of events 8 • 8.5 months
|
5.9%
1/17 • Number of events 1 • 8.5 months
|
Additional Information
Wipa Chawachalasai
U.S. Army Medical Component Armed Forces Research Institute of Medical Services
Phone: 662-696-2700
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place