Trial Outcomes & Findings for A/H5N1/LT Dose Ranging Study (NCT NCT00908687)
NCT ID: NCT00908687
Last Updated: 2021-12-10
Results Overview
Seroconversion is defined as either 1) baseline HI titer \< 1:10 and a post-vaccination HI titer ≥ 1:40, or 2) baseline HI titer ≥ 1:10 and a minimum four-fold rise. Seroprotection is defined as a post-vaccination HI antibody titer ≥ 1:40. FDA/EMEA criterion for seroconversion was to meet or exceed 40%. FDA/EMEA criterion for seroprotection was to meet or exceed 70%.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
500 participants
Primary outcome timeframe
Day 28
Results posted on
2021-12-10
Participant Flow
Participant milestones
| Measure |
Group 1: 30 µg HA, no LT Patch
A/H5N1 Vaccine 30 µg HA i.m. on Day 0
A/H5N1: A/H5N1 Low Dose
|
Group 2: 30 µg HA + 50 µg LT Patch
A/H5N1 Vaccine 30 µg HA i.m. + LT adjuvant patch containing 50 µg of LT on Day 0
A/H5N1: A/H5N1 Low Dose
LT Adjuvant Patch: LT Adjuvant Patch Low Dose
|
Group 3: 30 µg HA + 100 µg LT Patch
A/H5N1 Vaccine 30 µg HA i.m. + LT adjuvant patch containing 100 µg of LT on Day 0
A/H5N1: A/H5N1 Low Dose
LT Adjuvant Patch: LT Adjuvant Patch High Dose
|
Group 4: 45 µg HA, no LT Patch
A/H5N1 Vaccine 45 µg HA i.m. on Day 0
A/H5N1: A/H5N1 High Dose
|
Group 5: 45 µg HA + 50 µg LT Patch
A/H5N1 Vaccine 45 µg HA i.m. + LT adjuvant patch containing 50 µg of LT on Day 0
A/H5N1: A/H5N1 High Dose
LT Adjuvant Patch: LT Adjuvant Patch Low Dose
|
Group 6: 45 µg HA + 100 µg LT Patch
A/H5N1 Vaccine 45 µg HA i.m. + LT adjuvant patch containing 100 µg of LT on Day 0
A/H5N1: A/H5N1 High Dose
LT Adjuvant Patch: LT Adjuvant Patch High Dose
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
50
|
100
|
102
|
50
|
98
|
100
|
|
Overall Study
COMPLETED
|
49
|
99
|
99
|
47
|
94
|
94
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
3
|
3
|
4
|
6
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A/H5N1/LT Dose Ranging Study
Baseline characteristics by cohort
| Measure |
Group 1: 30 µg HA, no LT Patch
n=50 Participants
A/H5N1 Vaccine 30 µg HA i.m. on Day 0
A/H5N1: A/H5N1 Low Dose
|
Group 2: 30 µg HA + 50 µg LT Patch
n=100 Participants
A/H5N1 Vaccine 30 µg HA i.m. + LT adjuvant patch containing 50 µg of LT on Day 0
A/H5N1: A/H5N1 Low Dose
LT Adjuvant Patch: LT Adjuvant Patch Low Dose
|
Group 3: 30 µg HA + 100 µg LT Patch
n=102 Participants
A/H5N1 Vaccine 30 µg HA i.m. + LT adjuvant patch containing 100 µg of LT on Day 0
A/H5N1: A/H5N1 Low Dose
LT Adjuvant Patch: LT Adjuvant Patch High Dose
|
Group 4: 45 µg HA, no LT Patch
n=50 Participants
A/H5N1 Vaccine 45 µg HA i.m. on Day 0
A/H5N1: A/H5N1 High Dose
|
Group 5: 45 µg HA + 50 µg LT Patch
n=98 Participants
A/H5N1 Vaccine 45 µg HA i.m. + LT adjuvant patch containing 50 µg of LT on Day 0
A/H5N1: A/H5N1 High Dose
LT Adjuvant Patch: LT Adjuvant Patch Low Dose
|
Group 6: 45 µg HA + 100 µg LT Patch
n=100 Participants
A/H5N1 Vaccine 45 µg HA i.m. + LT adjuvant patch containing 100 µg of LT on Day 0
A/H5N1: A/H5N1 High Dose
LT Adjuvant Patch: LT Adjuvant Patch High Dose
|
Total
n=500 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
30.9 years
STANDARD_DEVIATION 9.7 • n=5 Participants
|
29.8 years
STANDARD_DEVIATION 9.6 • n=7 Participants
|
31.3 years
STANDARD_DEVIATION 10.4 • n=5 Participants
|
30.5 years
STANDARD_DEVIATION 8.7 • n=4 Participants
|
28.1 years
STANDARD_DEVIATION 8.2 • n=21 Participants
|
30.8 years
STANDARD_DEVIATION 8.3 • n=10 Participants
|
30.1 years
STANDARD_DEVIATION 9.2 • n=115 Participants
|
|
Sex: Female, Male
Female
|
29 Participants
n=5 Participants
|
54 Participants
n=7 Participants
|
61 Participants
n=5 Participants
|
25 Participants
n=4 Participants
|
53 Participants
n=21 Participants
|
64 Participants
n=10 Participants
|
286 Participants
n=115 Participants
|
|
Sex: Female, Male
Male
|
21 Participants
n=5 Participants
|
46 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
25 Participants
n=4 Participants
|
45 Participants
n=21 Participants
|
36 Participants
n=10 Participants
|
214 Participants
n=115 Participants
|
PRIMARY outcome
Timeframe: Day 28Population: Primary Immunogenicity Evaluable Population (PIEP): all subjects who were consented, randomized, received the assigned treatment, had HI assay results at all the following time points: baseline (Day 0), Day 21 and Day 28, and did not have any major protocol deviations
Seroconversion is defined as either 1) baseline HI titer \< 1:10 and a post-vaccination HI titer ≥ 1:40, or 2) baseline HI titer ≥ 1:10 and a minimum four-fold rise. Seroprotection is defined as a post-vaccination HI antibody titer ≥ 1:40. FDA/EMEA criterion for seroconversion was to meet or exceed 40%. FDA/EMEA criterion for seroprotection was to meet or exceed 70%.
Outcome measures
| Measure |
Group 1: 30 µg HA, no LT Patch
n=49 Participants
A/H5N1 Vaccine 30 µg HA i.m. on Day 0
A/H5N1: A/H5N1 Low Dose
|
Group 2: 30 µg HA + 50 µg LT Patch
n=98 Participants
A/H5N1 Vaccine 30 µg HA i.m. + LT adjuvant patch containing 50 µg of LT on Day 0
A/H5N1: A/H5N1 Low Dose
LT Adjuvant Patch: LT Adjuvant Patch Low Dose
|
Group 3: 30 µg HA + 100 µg LT Patch
n=101 Participants
A/H5N1 Vaccine 30 µg HA i.m. + LT adjuvant patch containing 100 µg of LT on Day 0
A/H5N1: A/H5N1 Low Dose
LT Adjuvant Patch: LT Adjuvant Patch High Dose
|
Group 4: 45 µg HA, no LT Patch
n=50 Participants
A/H5N1 Vaccine 45 µg HA i.m. on Day 0
A/H5N1: A/H5N1 High Dose
|
Group 5: 45 µg HA + 50 µg LT Patch
n=96 Participants
A/H5N1 Vaccine 45 µg HA i.m. + LT adjuvant patch containing 50 µg of LT on Day 0
A/H5N1: A/H5N1 High Dose
LT Adjuvant Patch: LT Adjuvant Patch Low Dose
|
Group 6: 45 µg HA + 100 µg LT Patch
n=94 Participants
A/H5N1 Vaccine 45 µg HA i.m. + LT adjuvant patch containing 100 µg of LT on Day 0
A/H5N1: A/H5N1 High Dose
LT Adjuvant Patch: LT Adjuvant Patch High Dose
|
|---|---|---|---|---|---|---|
|
Assess the Proportion of Subjects in Each Dose Group Achieving Seroconversion and Seroprotection for HI Antibody Titer Through Day 28.
HI Seroconversion Rates
|
35.4 percentage of subjects
Interval 22.2 to 50.5
|
47.4 percentage of subjects
Interval 37.2 to 57.8
|
37.6 percentage of subjects
Interval 28.2 to 47.8
|
53.1 percentage of subjects
Interval 38.3 to 67.5
|
50.5 percentage of subjects
Interval 40.1 to 61.0
|
50.0 percentage of subjects
Interval 39.5 to 60.5
|
|
Assess the Proportion of Subjects in Each Dose Group Achieving Seroconversion and Seroprotection for HI Antibody Titer Through Day 28.
HI Seroprotection Rates
|
35.4 percentage of subjects
Interval 22.2 to 50.5
|
47.4 percentage of subjects
Interval 37.2 to 57.8
|
37.6 percentage of subjects
Interval 28.2 to 47.8
|
55.1 percentage of subjects
Interval 40.2 to 69.3
|
53.7 percentage of subjects
Interval 43.2 to 64.0
|
50.0 percentage of subjects
Interval 39.5 to 60.5
|
SECONDARY outcome
Timeframe: 6 monthsOutcome measures
| Measure |
Group 1: 30 µg HA, no LT Patch
n=50 Participants
A/H5N1 Vaccine 30 µg HA i.m. on Day 0
A/H5N1: A/H5N1 Low Dose
|
Group 2: 30 µg HA + 50 µg LT Patch
n=100 Participants
A/H5N1 Vaccine 30 µg HA i.m. + LT adjuvant patch containing 50 µg of LT on Day 0
A/H5N1: A/H5N1 Low Dose
LT Adjuvant Patch: LT Adjuvant Patch Low Dose
|
Group 3: 30 µg HA + 100 µg LT Patch
n=102 Participants
A/H5N1 Vaccine 30 µg HA i.m. + LT adjuvant patch containing 100 µg of LT on Day 0
A/H5N1: A/H5N1 Low Dose
LT Adjuvant Patch: LT Adjuvant Patch High Dose
|
Group 4: 45 µg HA, no LT Patch
n=50 Participants
A/H5N1 Vaccine 45 µg HA i.m. on Day 0
A/H5N1: A/H5N1 High Dose
|
Group 5: 45 µg HA + 50 µg LT Patch
n=98 Participants
A/H5N1 Vaccine 45 µg HA i.m. + LT adjuvant patch containing 50 µg of LT on Day 0
A/H5N1: A/H5N1 High Dose
LT Adjuvant Patch: LT Adjuvant Patch Low Dose
|
Group 6: 45 µg HA + 100 µg LT Patch
n=100 Participants
A/H5N1 Vaccine 45 µg HA i.m. + LT adjuvant patch containing 100 µg of LT on Day 0
A/H5N1: A/H5N1 High Dose
LT Adjuvant Patch: LT Adjuvant Patch High Dose
|
|---|---|---|---|---|---|---|
|
Safety of A/H5N1 Vaccine IM Injection With and Without an LT Adjuvant Patch
All Serious AEs
|
0 Number of Events
|
0 Number of Events
|
1 Number of Events
|
0 Number of Events
|
1 Number of Events
|
1 Number of Events
|
|
Safety of A/H5N1 Vaccine IM Injection With and Without an LT Adjuvant Patch
All AEs
|
70 Number of Events
|
484 Number of Events
|
507 Number of Events
|
136 Number of Events
|
516 Number of Events
|
471 Number of Events
|
|
Safety of A/H5N1 Vaccine IM Injection With and Without an LT Adjuvant Patch
Local AEs
|
19 Number of Events
|
309 Number of Events
|
358 Number of Events
|
37 Number of Events
|
361 Number of Events
|
337 Number of Events
|
|
Safety of A/H5N1 Vaccine IM Injection With and Without an LT Adjuvant Patch
Systemic AEs
|
51 Number of Events
|
175 Number of Events
|
149 Number of Events
|
99 Number of Events
|
155 Number of Events
|
134 Number of Events
|
|
Safety of A/H5N1 Vaccine IM Injection With and Without an LT Adjuvant Patch
All Severe AEs
|
4 Number of Events
|
28 Number of Events
|
13 Number of Events
|
6 Number of Events
|
26 Number of Events
|
28 Number of Events
|
|
Safety of A/H5N1 Vaccine IM Injection With and Without an LT Adjuvant Patch
Severe Local AEs
|
0 Number of Events
|
18 Number of Events
|
11 Number of Events
|
0 Number of Events
|
18 Number of Events
|
21 Number of Events
|
|
Safety of A/H5N1 Vaccine IM Injection With and Without an LT Adjuvant Patch
Related Severe Local AEs
|
0 Number of Events
|
18 Number of Events
|
11 Number of Events
|
0 Number of Events
|
18 Number of Events
|
21 Number of Events
|
|
Safety of A/H5N1 Vaccine IM Injection With and Without an LT Adjuvant Patch
Severe Systemic AEs
|
4 Number of Events
|
10 Number of Events
|
2 Number of Events
|
6 Number of Events
|
8 Number of Events
|
7 Number of Events
|
|
Safety of A/H5N1 Vaccine IM Injection With and Without an LT Adjuvant Patch
Related Severe Systemic AEs
|
2 Number of Events
|
4 Number of Events
|
0 Number of Events
|
1 Number of Events
|
4 Number of Events
|
3 Number of Events
|
|
Safety of A/H5N1 Vaccine IM Injection With and Without an LT Adjuvant Patch
Serious Local AEs
|
0 Number of Events
|
0 Number of Events
|
0 Number of Events
|
0 Number of Events
|
0 Number of Events
|
0 Number of Events
|
|
Safety of A/H5N1 Vaccine IM Injection With and Without an LT Adjuvant Patch
Serious Systemic AEs
|
0 Number of Events
|
0 Number of Events
|
1 Number of Events
|
0 Number of Events
|
1 Number of Events
|
1 Number of Events
|
SECONDARY outcome
Timeframe: Day 28Outcome measures
| Measure |
Group 1: 30 µg HA, no LT Patch
n=49 Participants
A/H5N1 Vaccine 30 µg HA i.m. on Day 0
A/H5N1: A/H5N1 Low Dose
|
Group 2: 30 µg HA + 50 µg LT Patch
n=98 Participants
A/H5N1 Vaccine 30 µg HA i.m. + LT adjuvant patch containing 50 µg of LT on Day 0
A/H5N1: A/H5N1 Low Dose
LT Adjuvant Patch: LT Adjuvant Patch Low Dose
|
Group 3: 30 µg HA + 100 µg LT Patch
n=101 Participants
A/H5N1 Vaccine 30 µg HA i.m. + LT adjuvant patch containing 100 µg of LT on Day 0
A/H5N1: A/H5N1 Low Dose
LT Adjuvant Patch: LT Adjuvant Patch High Dose
|
Group 4: 45 µg HA, no LT Patch
n=50 Participants
A/H5N1 Vaccine 45 µg HA i.m. on Day 0
A/H5N1: A/H5N1 High Dose
|
Group 5: 45 µg HA + 50 µg LT Patch
n=96 Participants
A/H5N1 Vaccine 45 µg HA i.m. + LT adjuvant patch containing 50 µg of LT on Day 0
A/H5N1: A/H5N1 High Dose
LT Adjuvant Patch: LT Adjuvant Patch Low Dose
|
Group 6: 45 µg HA + 100 µg LT Patch
n=94 Participants
A/H5N1 Vaccine 45 µg HA i.m. + LT adjuvant patch containing 100 µg of LT on Day 0
A/H5N1: A/H5N1 High Dose
LT Adjuvant Patch: LT Adjuvant Patch High Dose
|
|---|---|---|---|---|---|---|
|
Evaluate Treatment Group HI Responses Against US FDA Guidance for Industry: Clinical Data Needed to Support the Licensure of Pandemic Influenza Vaccines (May 2007) and EMA CPMP/BWP/214/96 Criteria for Immunogenicity
|
7.1 fold increase of Geometric Mean Titers
Interval 4.8 to 10.5
|
8.4 fold increase of Geometric Mean Titers
Interval 6.2 to 11.3
|
8.6 fold increase of Geometric Mean Titers
Interval 6.4 to 11.6
|
12.7 fold increase of Geometric Mean Titers
Interval 8.5 to 19.2
|
10.7 fold increase of Geometric Mean Titers
Interval 8.0 to 14.2
|
13.5 fold increase of Geometric Mean Titers
Interval 9.7 to 18.7
|
Adverse Events
Group 1: 30 µg HA, no LT Patch
Serious events: 0 serious events
Other events: 31 other events
Deaths: 0 deaths
Group 2: 30 µg HA + 50 µg LT Patch
Serious events: 0 serious events
Other events: 86 other events
Deaths: 0 deaths
Group 3: 30 µg HA + 100 µg LT Patch
Serious events: 1 serious events
Other events: 86 other events
Deaths: 0 deaths
Group 4: 45 µg HA, no LT Patch
Serious events: 0 serious events
Other events: 36 other events
Deaths: 0 deaths
Group 5: 45 µg HA + 50 µg LT Patch
Serious events: 1 serious events
Other events: 87 other events
Deaths: 0 deaths
Group 6: 45 µg HA + 100 µg LT Patch
Serious events: 1 serious events
Other events: 85 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Group 1: 30 µg HA, no LT Patch
n=50 participants at risk
A/H5N1 Vaccine 30 µg HA i.m. on Day 0
A/H5N1: A/H5N1 Low Dose
|
Group 2: 30 µg HA + 50 µg LT Patch
n=100 participants at risk
A/H5N1 Vaccine 30 µg HA i.m. + LT adjuvant patch containing 50 µg of LT on Day 0
A/H5N1: A/H5N1 Low Dose
LT Adjuvant Patch: LT Adjuvant Patch Low Dose
|
Group 3: 30 µg HA + 100 µg LT Patch
n=102 participants at risk
A/H5N1 Vaccine 30 µg HA i.m. + LT adjuvant patch containing 100 µg of LT on Day 0
A/H5N1: A/H5N1 Low Dose
LT Adjuvant Patch: LT Adjuvant Patch High Dose
|
Group 4: 45 µg HA, no LT Patch
n=50 participants at risk
A/H5N1 Vaccine 45 µg HA i.m. on Day 0
A/H5N1: A/H5N1 High Dose
|
Group 5: 45 µg HA + 50 µg LT Patch
n=98 participants at risk
A/H5N1 Vaccine 45 µg HA i.m. + LT adjuvant patch containing 50 µg of LT on Day 0
A/H5N1: A/H5N1 High Dose
LT Adjuvant Patch: LT Adjuvant Patch Low Dose
|
Group 6: 45 µg HA + 100 µg LT Patch
n=100 participants at risk
A/H5N1 Vaccine 45 µg HA i.m. + LT adjuvant patch containing 100 µg of LT on Day 0
A/H5N1: A/H5N1 High Dose
LT Adjuvant Patch: LT Adjuvant Patch High Dose
|
|---|---|---|---|---|---|---|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/50
|
0.00%
0/100
|
0.00%
0/102
|
0.00%
0/50
|
1.0%
1/98
|
0.00%
0/100
|
|
Reproductive system and breast disorders
Adenomyosis
|
0.00%
0/50
|
0.00%
0/100
|
0.00%
0/102
|
0.00%
0/50
|
0.00%
0/98
|
1.0%
1/100
|
|
Vascular disorders
Hypotension
|
0.00%
0/50
|
0.00%
0/100
|
0.98%
1/102
|
0.00%
0/50
|
0.00%
0/98
|
0.00%
0/100
|
Other adverse events
| Measure |
Group 1: 30 µg HA, no LT Patch
n=50 participants at risk
A/H5N1 Vaccine 30 µg HA i.m. on Day 0
A/H5N1: A/H5N1 Low Dose
|
Group 2: 30 µg HA + 50 µg LT Patch
n=100 participants at risk
A/H5N1 Vaccine 30 µg HA i.m. + LT adjuvant patch containing 50 µg of LT on Day 0
A/H5N1: A/H5N1 Low Dose
LT Adjuvant Patch: LT Adjuvant Patch Low Dose
|
Group 3: 30 µg HA + 100 µg LT Patch
n=102 participants at risk
A/H5N1 Vaccine 30 µg HA i.m. + LT adjuvant patch containing 100 µg of LT on Day 0
A/H5N1: A/H5N1 Low Dose
LT Adjuvant Patch: LT Adjuvant Patch High Dose
|
Group 4: 45 µg HA, no LT Patch
n=50 participants at risk
A/H5N1 Vaccine 45 µg HA i.m. on Day 0
A/H5N1: A/H5N1 High Dose
|
Group 5: 45 µg HA + 50 µg LT Patch
n=98 participants at risk
A/H5N1 Vaccine 45 µg HA i.m. + LT adjuvant patch containing 50 µg of LT on Day 0
A/H5N1: A/H5N1 High Dose
LT Adjuvant Patch: LT Adjuvant Patch Low Dose
|
Group 6: 45 µg HA + 100 µg LT Patch
n=100 participants at risk
A/H5N1 Vaccine 45 µg HA i.m. + LT adjuvant patch containing 100 µg of LT on Day 0
A/H5N1: A/H5N1 High Dose
LT Adjuvant Patch: LT Adjuvant Patch High Dose
|
|---|---|---|---|---|---|---|
|
Nervous system disorders
Headache
|
8.0%
4/50
|
19.0%
19/100
|
12.7%
13/102
|
20.0%
10/50
|
10.2%
10/98
|
9.0%
9/100
|
|
General disorders
Malaise
|
6.0%
3/50
|
13.0%
13/100
|
5.9%
6/102
|
18.0%
9/50
|
9.2%
9/98
|
7.0%
7/100
|
|
Gastrointestinal disorders
Diarrhea
|
8.0%
4/50
|
13.0%
13/100
|
15.7%
16/102
|
8.0%
4/50
|
15.3%
15/98
|
15.0%
15/100
|
|
General disorders
Chills
|
0.00%
0/50
|
2.0%
2/100
|
2.9%
3/102
|
6.0%
3/50
|
2.0%
2/98
|
3.0%
3/100
|
|
Gastrointestinal disorders
Nausea
|
10.0%
5/50
|
11.0%
11/100
|
5.9%
6/102
|
10.0%
5/50
|
12.2%
12/98
|
6.0%
6/100
|
|
Injury, poisoning and procedural complications
Vaccination site erythema
|
4.0%
2/50
|
49.0%
49/100
|
50.0%
51/102
|
6.0%
3/50
|
55.1%
54/98
|
53.0%
53/100
|
|
Injury, poisoning and procedural complications
Vaccination site rash
|
0.00%
0/50
|
45.0%
45/100
|
55.9%
57/102
|
4.0%
2/50
|
59.2%
58/98
|
55.0%
55/100
|
|
Injury, poisoning and procedural complications
Vaccination site hyperpigmentation
|
0.00%
0/50
|
22.0%
22/100
|
26.5%
27/102
|
0.00%
0/50
|
25.5%
25/98
|
25.0%
25/100
|
|
Injury, poisoning and procedural complications
Vaccination site edema
|
2.0%
1/50
|
12.0%
12/100
|
15.7%
16/102
|
2.0%
1/50
|
11.2%
11/98
|
10.0%
10/100
|
|
Injury, poisoning and procedural complications
Vaccination site pain
|
14.0%
7/50
|
32.0%
32/100
|
40.2%
41/102
|
26.0%
13/50
|
35.7%
35/98
|
33.0%
33/100
|
|
Injury, poisoning and procedural complications
Vaccination site induration
|
12.0%
6/50
|
13.0%
13/100
|
14.7%
15/102
|
16.0%
8/50
|
15.3%
15/98
|
12.0%
12/100
|
|
Injury, poisoning and procedural complications
Vaccination site eccymosis
|
2.0%
1/50
|
5.0%
5/100
|
10.8%
11/102
|
2.0%
1/50
|
7.1%
7/98
|
6.0%
6/100
|
|
Injury, poisoning and procedural complications
Vaccination site pruritis
|
2.0%
1/50
|
45.0%
45/100
|
52.0%
53/102
|
10.0%
5/50
|
52.0%
51/98
|
54.0%
54/100
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER