Trial Outcomes & Findings for Systems Biology of Influenza A (H5N1) Virus Monovalent Vaccine With and Without Adjuvant System 03 (AS03) (NCT NCT01910519)
NCT ID: NCT01910519
Last Updated: 2019-02-12
Results Overview
To identify innate immune signatures; 1 day post first vaccination
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
50 participants
Primary outcome timeframe
Day 1
Results posted on
2019-02-12
Participant Flow
Patients were randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant undergoing scheduled anterior cruciate ligament (ACL) surgery at the Hope Clinic - Emory Vaccine Center in Decatur, Georgia. Participants were enrolled between July 2013 and January 2014.
Of the 99 screened participants, 50 were enrolled and vaccinated. 2 participants withdrew from the study.
Participant milestones
| Measure |
Influenza A (H5N1) Virus Monovalent Vaccine With AS03 Adjuvant
Participants randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine with AS03 adjuvant
|
Influenza A (H5N1) Virus Monovalent Vaccine Without AS03 Adjuv
Participants randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine without AS03 adjuvant
|
|---|---|---|
|
Overall Study
STARTED
|
35
|
15
|
|
Overall Study
COMPLETED
|
31
|
15
|
|
Overall Study
NOT COMPLETED
|
4
|
0
|
Reasons for withdrawal
| Measure |
Influenza A (H5N1) Virus Monovalent Vaccine With AS03 Adjuvant
Participants randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine with AS03 adjuvant
|
Influenza A (H5N1) Virus Monovalent Vaccine Without AS03 Adjuv
Participants randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine without AS03 adjuvant
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
0
|
|
Overall Study
Adverse Event
|
2
|
0
|
Baseline Characteristics
Systems Biology of Influenza A (H5N1) Virus Monovalent Vaccine With and Without Adjuvant System 03 (AS03)
Baseline characteristics by cohort
| Measure |
Influenza A (H5N1) Virus Monovalent Vaccine With AS03 Adjuvant
n=35 Participants
Participants randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine with AS03 adjuvant
|
Influenza A (H5N1) Virus Monovalent Vaccine Without AS03 Adjuv
n=15 Participants
Participants randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine without AS03 adjuvant
|
Total
n=50 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
35 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
50 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
22 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
35 participants
n=5 Participants
|
15 participants
n=7 Participants
|
50 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 1To identify innate immune signatures; 1 day post first vaccination
Outcome measures
| Measure |
Influenza A (H5N1) Virus Monovalent Vaccine With AS03 Adjuvant
n=35 Participants
Participants randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine with AS03 adjuvant
|
Influenza A (H5N1) Virus Monovalent Vaccine Without AS03 Adjuv
n=15 Participants
Participants randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine without AS03 adjuvant
|
|---|---|---|
|
Change in Traditional Immune Parameters Measurements Using Luminex Assays and Gene Expression Measurement Using Microarray Experiments From Baseline With Influenza A Vaccine With and Without AS03 Adjuvant
Upregulated
|
1434 differentially expressed genes (DEGs)
|
128 differentially expressed genes (DEGs)
|
|
Change in Traditional Immune Parameters Measurements Using Luminex Assays and Gene Expression Measurement Using Microarray Experiments From Baseline With Influenza A Vaccine With and Without AS03 Adjuvant
Downregulated
|
1768 differentially expressed genes (DEGs)
|
56 differentially expressed genes (DEGs)
|
PRIMARY outcome
Timeframe: Day 3To identify innate immune signatures; 3 days post first vaccination
Outcome measures
| Measure |
Influenza A (H5N1) Virus Monovalent Vaccine With AS03 Adjuvant
n=35 Participants
Participants randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine with AS03 adjuvant
|
Influenza A (H5N1) Virus Monovalent Vaccine Without AS03 Adjuv
n=15 Participants
Participants randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine without AS03 adjuvant
|
|---|---|---|
|
Change in Traditional Immune Parameters Measurements Using Luminex Assays and Gene Expression Measurement Using Microarray Experiments From Baseline With Influenza A Vaccine With and Without AS03 Adjuvant
Upregulated
|
654 differentially expressed genes (DEGs)
|
787 differentially expressed genes (DEGs)
|
|
Change in Traditional Immune Parameters Measurements Using Luminex Assays and Gene Expression Measurement Using Microarray Experiments From Baseline With Influenza A Vaccine With and Without AS03 Adjuvant
Downregulated
|
445 differentially expressed genes (DEGs)
|
620 differentially expressed genes (DEGs)
|
PRIMARY outcome
Timeframe: Day 7To identify innate immune signatures; 7 days post first vaccination
Outcome measures
| Measure |
Influenza A (H5N1) Virus Monovalent Vaccine With AS03 Adjuvant
n=35 Participants
Participants randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine with AS03 adjuvant
|
Influenza A (H5N1) Virus Monovalent Vaccine Without AS03 Adjuv
n=15 Participants
Participants randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine without AS03 adjuvant
|
|---|---|---|
|
Change in Traditional Immune Parameters Measurements Using Luminex Assays and Gene Expression Measurement Using Microarray Experiments From Baseline With Influenza A Vaccine With and Without AS03 Adjuvant
Upregulated
|
149 differentially expressed genes (DEGs)
|
83 differentially expressed genes (DEGs)
|
|
Change in Traditional Immune Parameters Measurements Using Luminex Assays and Gene Expression Measurement Using Microarray Experiments From Baseline With Influenza A Vaccine With and Without AS03 Adjuvant
Downregulated
|
232 differentially expressed genes (DEGs)
|
178 differentially expressed genes (DEGs)
|
PRIMARY outcome
Timeframe: Day 22To identify innate immune signatures; 1 day post second vaccination
Outcome measures
| Measure |
Influenza A (H5N1) Virus Monovalent Vaccine With AS03 Adjuvant
n=35 Participants
Participants randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine with AS03 adjuvant
|
Influenza A (H5N1) Virus Monovalent Vaccine Without AS03 Adjuv
n=15 Participants
Participants randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine without AS03 adjuvant
|
|---|---|---|
|
Change in Traditional Immune Parameters Measurements Using Luminex Assays and Gene Expression Measurement Using Microarray Experiments From Baseline With Influenza A Vaccine With and Without AS03 Adjuvant
Upregulated
|
1953 differentially expressed genes (DEGs)
|
81 differentially expressed genes (DEGs)
|
|
Change in Traditional Immune Parameters Measurements Using Luminex Assays and Gene Expression Measurement Using Microarray Experiments From Baseline With Influenza A Vaccine With and Without AS03 Adjuvant
Downregulated
|
2820 differentially expressed genes (DEGs)
|
99 differentially expressed genes (DEGs)
|
PRIMARY outcome
Timeframe: Day 24To identify innate immune signatures; 3 days post second vaccination
Outcome measures
| Measure |
Influenza A (H5N1) Virus Monovalent Vaccine With AS03 Adjuvant
n=35 Participants
Participants randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine with AS03 adjuvant
|
Influenza A (H5N1) Virus Monovalent Vaccine Without AS03 Adjuv
n=15 Participants
Participants randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine without AS03 adjuvant
|
|---|---|---|
|
Change in Traditional Immune Parameters Measurements Using Luminex Assays and Gene Expression Measurement Using Microarray Experiments From Baseline With Influenza A Vaccine With and Without AS03 Adjuvant
Upregulated
|
839 differentially expressed genes (DEGs)
|
78 differentially expressed genes (DEGs)
|
|
Change in Traditional Immune Parameters Measurements Using Luminex Assays and Gene Expression Measurement Using Microarray Experiments From Baseline With Influenza A Vaccine With and Without AS03 Adjuvant
Downregulated
|
487 differentially expressed genes (DEGs)
|
172 differentially expressed genes (DEGs)
|
PRIMARY outcome
Timeframe: Day 28To identify innate immune signatures; 7 days post second vaccination
Outcome measures
| Measure |
Influenza A (H5N1) Virus Monovalent Vaccine With AS03 Adjuvant
n=35 Participants
Participants randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine with AS03 adjuvant
|
Influenza A (H5N1) Virus Monovalent Vaccine Without AS03 Adjuv
n=15 Participants
Participants randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine without AS03 adjuvant
|
|---|---|---|
|
Change in Traditional Immune Parameters Measurements Using Luminex Assays and Gene Expression Measurement Using Microarray Experiments From Baseline With Influenza A Vaccine With and Without AS03 Adjuvant
Upregulated
|
63 differentially expressed genes (DEGs)
|
34 differentially expressed genes (DEGs)
|
|
Change in Traditional Immune Parameters Measurements Using Luminex Assays and Gene Expression Measurement Using Microarray Experiments From Baseline With Influenza A Vaccine With and Without AS03 Adjuvant
Downregulated
|
28 differentially expressed genes (DEGs)
|
52 differentially expressed genes (DEGs)
|
PRIMARY outcome
Timeframe: Day 21To measure selective adaptive immune response; 21 days post first vaccination
Outcome measures
| Measure |
Influenza A (H5N1) Virus Monovalent Vaccine With AS03 Adjuvant
n=35 Participants
Participants randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine with AS03 adjuvant
|
Influenza A (H5N1) Virus Monovalent Vaccine Without AS03 Adjuv
n=15 Participants
Participants randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine without AS03 adjuvant
|
|---|---|---|
|
Measurement of Hemagglutination Inhibition Assay (HAI) Titers With Influenza A Vaccine With and Without AS03 Adjuvant
|
5.561 IU/ml
Interval 4.976 to 6.213
|
5 IU/ml
Interval 5.0 to 5.0
|
PRIMARY outcome
Timeframe: Day 21To measure selective adaptive immune response; 21 days post first vaccination
Outcome measures
| Measure |
Influenza A (H5N1) Virus Monovalent Vaccine With AS03 Adjuvant
n=35 Participants
Participants randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine with AS03 adjuvant
|
Influenza A (H5N1) Virus Monovalent Vaccine Without AS03 Adjuv
n=15 Participants
Participants randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine without AS03 adjuvant
|
|---|---|---|
|
Measurement of Microneutralization (MN) Titers With Influenza A Vaccine With and Without AS03 Adjuvant
|
30.18 IU/ml
Interval 23.08 to 39.47
|
10.44 IU/ml
Interval 9.522 to 11.45
|
PRIMARY outcome
Timeframe: Day 42To measure selective adaptive immune response; 21 days post second vaccination
Outcome measures
| Measure |
Influenza A (H5N1) Virus Monovalent Vaccine With AS03 Adjuvant
n=35 Participants
Participants randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine with AS03 adjuvant
|
Influenza A (H5N1) Virus Monovalent Vaccine Without AS03 Adjuv
n=15 Participants
Participants randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine without AS03 adjuvant
|
|---|---|---|
|
Measurement of Hemagglutination Inhibition Assay (HAI) Titers With Influenza A Vaccine With and Without AS03 Adjuvant
|
41.3 IU/ml
Interval 26.19 to 65.12
|
5.183 IU/ml
Interval 4.919 to 5.462
|
PRIMARY outcome
Timeframe: Day 42To measure selective adaptive immune response; 21 days post second vaccination
Outcome measures
| Measure |
Influenza A (H5N1) Virus Monovalent Vaccine With AS03 Adjuvant
n=35 Participants
Participants randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine with AS03 adjuvant
|
Influenza A (H5N1) Virus Monovalent Vaccine Without AS03 Adjuv
n=15 Participants
Participants randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine without AS03 adjuvant
|
|---|---|---|
|
Measurement of Microneutralization (MN) Titers With Influenza A Vaccine With and Without AS03 Adjuvant
|
523.3 IU/ml
Interval 354.5 to 772.5
|
22.78 IU/ml
Interval 13.46 to 38.55
|
Adverse Events
Influenza A (H5N1) Virus Monovalent Vaccine With AS03 Adjuvant
Serious events: 1 serious events
Other events: 34 other events
Deaths: 0 deaths
Influenza A (H5N1) Virus Monovalent Vaccine Without AS03 Adjuv
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Influenza A (H5N1) Virus Monovalent Vaccine With AS03 Adjuvant
n=35 participants at risk
Participants randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine with AS03 adjuvant
|
Influenza A (H5N1) Virus Monovalent Vaccine Without AS03 Adjuv
n=15 participants at risk
Participants randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine without AS03 adjuvant
|
|---|---|---|
|
Pregnancy, puerperium and perinatal conditions
Missed abortion (unrelated to study vaccine)
|
2.9%
1/35 • Number of events 1 • Day 0 - Day 7 after 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant given 21 days apart.
Local and systemic reactogenicity after receipt of each vaccine
|
0.00%
0/15 • Day 0 - Day 7 after 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant given 21 days apart.
Local and systemic reactogenicity after receipt of each vaccine
|
Other adverse events
| Measure |
Influenza A (H5N1) Virus Monovalent Vaccine With AS03 Adjuvant
n=35 participants at risk
Participants randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine with AS03 adjuvant
|
Influenza A (H5N1) Virus Monovalent Vaccine Without AS03 Adjuv
n=15 participants at risk
Participants randomized to receive Influenza A (H5N1) Virus Monovalent Vaccine without AS03 adjuvant
|
|---|---|---|
|
General disorders
Body ache
|
37.1%
13/35 • Number of events 16 • Day 0 - Day 7 after 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant given 21 days apart.
Local and systemic reactogenicity after receipt of each vaccine
|
13.3%
2/15 • Number of events 2 • Day 0 - Day 7 after 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant given 21 days apart.
Local and systemic reactogenicity after receipt of each vaccine
|
|
Blood and lymphatic system disorders
Anemia
|
5.7%
2/35 • Number of events 2 • Day 0 - Day 7 after 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant given 21 days apart.
Local and systemic reactogenicity after receipt of each vaccine
|
13.3%
2/15 • Number of events 2 • Day 0 - Day 7 after 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant given 21 days apart.
Local and systemic reactogenicity after receipt of each vaccine
|
|
Gastrointestinal disorders
Diarrhea
|
8.6%
3/35 • Number of events 3 • Day 0 - Day 7 after 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant given 21 days apart.
Local and systemic reactogenicity after receipt of each vaccine
|
0.00%
0/15 • Day 0 - Day 7 after 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant given 21 days apart.
Local and systemic reactogenicity after receipt of each vaccine
|
|
Immune system disorders
Allergic reaction
|
5.7%
2/35 • Number of events 2 • Day 0 - Day 7 after 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant given 21 days apart.
Local and systemic reactogenicity after receipt of each vaccine
|
6.7%
1/15 • Number of events 1 • Day 0 - Day 7 after 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant given 21 days apart.
Local and systemic reactogenicity after receipt of each vaccine
|
|
Infections and infestations
Upper Respiratory Infections
|
5.7%
2/35 • Number of events 2 • Day 0 - Day 7 after 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant given 21 days apart.
Local and systemic reactogenicity after receipt of each vaccine
|
0.00%
0/15 • Day 0 - Day 7 after 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant given 21 days apart.
Local and systemic reactogenicity after receipt of each vaccine
|
|
Musculoskeletal and connective tissue disorders
Joint pain
|
14.3%
5/35 • Number of events 5 • Day 0 - Day 7 after 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant given 21 days apart.
Local and systemic reactogenicity after receipt of each vaccine
|
0.00%
0/15 • Day 0 - Day 7 after 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant given 21 days apart.
Local and systemic reactogenicity after receipt of each vaccine
|
|
Renal and urinary disorders
Renal calculi
|
0.00%
0/35 • Day 0 - Day 7 after 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant given 21 days apart.
Local and systemic reactogenicity after receipt of each vaccine
|
6.7%
1/15 • Number of events 1 • Day 0 - Day 7 after 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant given 21 days apart.
Local and systemic reactogenicity after receipt of each vaccine
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
5.7%
2/35 • Number of events 2 • Day 0 - Day 7 after 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant given 21 days apart.
Local and systemic reactogenicity after receipt of each vaccine
|
6.7%
1/15 • Number of events 1 • Day 0 - Day 7 after 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant given 21 days apart.
Local and systemic reactogenicity after receipt of each vaccine
|
|
General disorders
Fever
|
2.9%
1/35 • Number of events 1 • Day 0 - Day 7 after 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant given 21 days apart.
Local and systemic reactogenicity after receipt of each vaccine
|
6.7%
1/15 • Number of events 2 • Day 0 - Day 7 after 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant given 21 days apart.
Local and systemic reactogenicity after receipt of each vaccine
|
|
General disorders
Nausea
|
8.6%
3/35 • Number of events 4 • Day 0 - Day 7 after 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant given 21 days apart.
Local and systemic reactogenicity after receipt of each vaccine
|
20.0%
3/15 • Number of events 3 • Day 0 - Day 7 after 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant given 21 days apart.
Local and systemic reactogenicity after receipt of each vaccine
|
|
General disorders
Malaise
|
0.00%
0/35 • Day 0 - Day 7 after 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant given 21 days apart.
Local and systemic reactogenicity after receipt of each vaccine
|
6.7%
1/15 • Number of events 1 • Day 0 - Day 7 after 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant given 21 days apart.
Local and systemic reactogenicity after receipt of each vaccine
|
|
General disorders
Vomiting
|
2.9%
1/35 • Number of events 1 • Day 0 - Day 7 after 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant given 21 days apart.
Local and systemic reactogenicity after receipt of each vaccine
|
0.00%
0/15 • Day 0 - Day 7 after 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant given 21 days apart.
Local and systemic reactogenicity after receipt of each vaccine
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place