Trial Outcomes & Findings for Phase 3 Trial of Serbian Seasonal Influenza Vaccine (NCT NCT02935192)
NCT ID: NCT02935192
Last Updated: 2019-04-19
Results Overview
Number of subjects reporting one or more solicited local reactions (redness/erythema, swelling/induration, pain, and tenderness) at the injection site post-vaccination with study vaccine or placebo
COMPLETED
PHASE3
480 participants
5-day period (Days 1-5) post-vaccination
2019-04-19
Participant Flow
503 subjects were consented and screened from across 6 clinical trial sites located in Belgrade and Vrsac, Serbia. Of the 503 subjects screened, 23 subjects failed screening.
Twenty-three (23) subjects failed screening and were not assigned to a treatment group. An additional 8 subjects withdrew consent prior to receiving any study product.
Participant milestones
| Measure |
Vaccine Arm
Trivalent seasonal influenza vaccine
|
Placebo Arm
Phosphate buffered saline
|
|---|---|---|
|
Overall Study
STARTED
|
320
|
160
|
|
Overall Study
Received Vaccine/Placebo
|
312
|
156
|
|
Overall Study
COMPLETED
|
312
|
156
|
|
Overall Study
NOT COMPLETED
|
8
|
4
|
Reasons for withdrawal
| Measure |
Vaccine Arm
Trivalent seasonal influenza vaccine
|
Placebo Arm
Phosphate buffered saline
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
8
|
4
|
Baseline Characteristics
Each row represents a subpopulation of age range for the study (18-44 years; 45-65 years). Together these totals add up to the overall study population in each arm.
Baseline characteristics by cohort
| Measure |
Vaccine
n=312 Participants
Seasonal trivalent split, inactivated influenza vaccine
Seasonal Influenza Vaccine: Seasonal trivalent split, inactivated influenza vaccine (A/H1N1; A/H3N2 and B); 0.5 mL by IM injection
|
Placebo
n=156 Participants
Phosphate buffered saline
Phosphate Buffered Saline: Phosphate buffered saline, 0.5 mL by IM injection
|
Total
n=468 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
18-44 years
|
32.8 years
n=232 Participants • Each row represents a subpopulation of age range for the study (18-44 years; 45-65 years). Together these totals add up to the overall study population in each arm.
|
32.0 years
n=116 Participants • Each row represents a subpopulation of age range for the study (18-44 years; 45-65 years). Together these totals add up to the overall study population in each arm.
|
32.6 years
n=348 Participants • Each row represents a subpopulation of age range for the study (18-44 years; 45-65 years). Together these totals add up to the overall study population in each arm.
|
|
Age, Continuous
45-65 years
|
54.7 years
n=80 Participants • Each row represents a subpopulation of age range for the study (18-44 years; 45-65 years). Together these totals add up to the overall study population in each arm.
|
53.8 years
n=40 Participants • Each row represents a subpopulation of age range for the study (18-44 years; 45-65 years). Together these totals add up to the overall study population in each arm.
|
54.4 years
n=120 Participants • Each row represents a subpopulation of age range for the study (18-44 years; 45-65 years). Together these totals add up to the overall study population in each arm.
|
|
Sex: Female, Male
Female
|
145 Participants
n=312 Participants
|
77 Participants
n=156 Participants
|
222 Participants
n=468 Participants
|
|
Sex: Female, Male
Male
|
167 Participants
n=312 Participants
|
79 Participants
n=156 Participants
|
246 Participants
n=468 Participants
|
|
Region of Enrollment
Serbia
|
312 participants
n=312 Participants
|
156 participants
n=156 Participants
|
468 participants
n=468 Participants
|
PRIMARY outcome
Timeframe: 30-minute post-vaccination periodPopulation: The analysis was conducted for subjects who were randomized and received a study vaccination
Number of participants experiencing one or more solicited local AEs, including redness /erythema, swelling / induration and pain
Outcome measures
| Measure |
Vaccine Arm
n=312 Participants
Trivalent seasonal influenza vaccine
|
Placebo Arm
n=156 Participants
Phosphate buffered saline
|
|---|---|---|
|
Number of Participants With Solicited Adverse Events (Local & Systemic Reactogenicity)
Hardness
|
5 Participants
|
1 Participants
|
|
Number of Participants With Solicited Adverse Events (Local & Systemic Reactogenicity)
Pain
|
5 Participants
|
0 Participants
|
|
Number of Participants With Solicited Adverse Events (Local & Systemic Reactogenicity)
Redness
|
22 Participants
|
3 Participants
|
|
Number of Participants With Solicited Adverse Events (Local & Systemic Reactogenicity)
Swelling
|
1 Participants
|
0 Participants
|
|
Number of Participants With Solicited Adverse Events (Local & Systemic Reactogenicity)
Tenderness
|
2 Participants
|
0 Participants
|
|
Number of Participants With Solicited Adverse Events (Local & Systemic Reactogenicity)
Temperature above 37 C
|
0 Participants
|
0 Participants
|
|
Number of Participants With Solicited Adverse Events (Local & Systemic Reactogenicity)
Chills
|
0 Participants
|
0 Participants
|
|
Number of Participants With Solicited Adverse Events (Local & Systemic Reactogenicity)
Headache
|
0 Participants
|
0 Participants
|
|
Number of Participants With Solicited Adverse Events (Local & Systemic Reactogenicity)
Joint aches
|
0 Participants
|
0 Participants
|
|
Number of Participants With Solicited Adverse Events (Local & Systemic Reactogenicity)
Muscle aches
|
0 Participants
|
0 Participants
|
|
Number of Participants With Solicited Adverse Events (Local & Systemic Reactogenicity)
Nausea
|
0 Participants
|
0 Participants
|
|
Number of Participants With Solicited Adverse Events (Local & Systemic Reactogenicity)
Tiredness
|
1 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: 5-day period (Days 1-5) post-vaccinationPopulation: Full analysis population
Number of subjects reporting one or more solicited local reactions (redness/erythema, swelling/induration, pain, and tenderness) at the injection site post-vaccination with study vaccine or placebo
Outcome measures
| Measure |
Vaccine Arm
n=312 Participants
Trivalent seasonal influenza vaccine
|
Placebo Arm
n=156 Participants
Phosphate buffered saline
|
|---|---|---|
|
Number of Participants With Solicited Local Adverse Events (Local Reactogenicity)
Hardness
|
29 Participants
|
0 Participants
|
|
Number of Participants With Solicited Local Adverse Events (Local Reactogenicity)
Pain
|
160 Participants
|
17 Participants
|
|
Number of Participants With Solicited Local Adverse Events (Local Reactogenicity)
Redness
|
40 Participants
|
3 Participants
|
|
Number of Participants With Solicited Local Adverse Events (Local Reactogenicity)
Swelling
|
20 Participants
|
0 Participants
|
|
Number of Participants With Solicited Local Adverse Events (Local Reactogenicity)
Tenderness
|
126 Participants
|
11 Participants
|
PRIMARY outcome
Timeframe: 5-day period (Days 1-5) post-vaccinationPopulation: Full analysis population
Number of subjects reporting one or more solicited systemic reactions (fever, fatigue/malaise, muscle aches, joint aches, chills, nausea, vomiting, and headache) post-vaccination with study vaccine or placebo.
Outcome measures
| Measure |
Vaccine Arm
n=312 Participants
Trivalent seasonal influenza vaccine
|
Placebo Arm
n=156 Participants
Phosphate buffered saline
|
|---|---|---|
|
Number of Participants With Solicited Systemic Adverse Events (Systemic Reactogenicity)
Chills
|
11 Participants
|
1 Participants
|
|
Number of Participants With Solicited Systemic Adverse Events (Systemic Reactogenicity)
Headache
|
47 Participants
|
19 Participants
|
|
Number of Participants With Solicited Systemic Adverse Events (Systemic Reactogenicity)
Joint Aches
|
16 Participants
|
5 Participants
|
|
Number of Participants With Solicited Systemic Adverse Events (Systemic Reactogenicity)
Muscle Aches
|
27 Participants
|
6 Participants
|
|
Number of Participants With Solicited Systemic Adverse Events (Systemic Reactogenicity)
Nausea
|
18 Participants
|
6 Participants
|
|
Number of Participants With Solicited Systemic Adverse Events (Systemic Reactogenicity)
Temperature
|
6 Participants
|
1 Participants
|
|
Number of Participants With Solicited Systemic Adverse Events (Systemic Reactogenicity)
Tiredness
|
53 Participants
|
16 Participants
|
PRIMARY outcome
Timeframe: Within 21 days post vaccinationPopulation: Full analysis population
Unsolicited AEs occurring in 1% or more of study participants; includes events irrespective of causality
Outcome measures
| Measure |
Vaccine Arm
n=312 Participants
Trivalent seasonal influenza vaccine
|
Placebo Arm
n=156 Participants
Phosphate buffered saline
|
|---|---|---|
|
Number of Participants With Unsolicited Adverse Events
Nasopharyngitis
|
3 Participants
|
4 Participants
|
|
Number of Participants With Unsolicited Adverse Events
Respiratory tract infection
|
7 Participants
|
1 Participants
|
|
Number of Participants With Unsolicited Adverse Events
Rhinitis
|
3 Participants
|
3 Participants
|
PRIMARY outcome
Timeframe: Over the entire study period (Day 91)Population: Full Analysis Population
Number of participants reporting one or more of all anticipated and unanticipated serious adverse events, grouped by organ system, with number and frequency of such events in each arm/group of the clinical study.
Outcome measures
| Measure |
Vaccine Arm
n=312 Participants
Trivalent seasonal influenza vaccine
|
Placebo Arm
n=156 Participants
Phosphate buffered saline
|
|---|---|---|
|
Number of Participants With Serious Adverse Events (SAE)
Acute Lymphocytic Leukemia · Related
|
0 Participants
|
0 Participants
|
|
Number of Participants With Serious Adverse Events (SAE)
Acute Lymphocytic Leukemia · Not related
|
1 Participants
|
0 Participants
|
|
Number of Participants With Serious Adverse Events (SAE)
Acute Lymphocytic Leukemia · Not reporting this SAE
|
311 Participants
|
156 Participants
|
|
Number of Participants With Serious Adverse Events (SAE)
Varicocele · Related
|
0 Participants
|
0 Participants
|
|
Number of Participants With Serious Adverse Events (SAE)
Varicocele · Not related
|
1 Participants
|
0 Participants
|
|
Number of Participants With Serious Adverse Events (SAE)
Varicocele · Not reporting this SAE
|
311 Participants
|
156 Participants
|
PRIMARY outcome
Timeframe: Day 22Population: Per Protocol (PP) Population: Immunogenicity was assessed in a subset of 151 participants (per-protocol population) with valid post-vaccination immunogenicity measures and no major protocol violations that were determined to potentially interfere with the immunogenicity assessment of the study vaccine. This was decided before unblinding.
Seroconversion is defined as a serum HAI antibody titer meeting the following criteria: * Pre-vaccination titer \<1:10 and a post-vaccination titer measured on Day 22 of ≥1:40; or * Pre-vaccination titer ≥1:10 and at least a four-fold increase in post-vaccination measured on Day 22. Measured against each of the 3 antigens
Outcome measures
| Measure |
Vaccine Arm
n=101 Participants
Trivalent seasonal influenza vaccine
|
Placebo Arm
n=50 Participants
Phosphate buffered saline
|
|---|---|---|
|
Number and Percentage of Seroconverted Subjects
Seroconversion to H3
|
77 Participants
|
0 Participants
|
|
Number and Percentage of Seroconverted Subjects
Seroconversion to H1
|
91 Participants
|
1 Participants
|
|
Number and Percentage of Seroconverted Subjects
Seroconversion to B
|
52 Participants
|
9 Participants
|
PRIMARY outcome
Timeframe: Day 1 and Day 22Population: Per Protocol (PP) Population: Immunogenicity was assessed in a subset of 151 participants (per-protocol population) with valid post-vaccination immunogenicity measures and no major protocol violations that were determined to potentially interfere with the immunogenicity assessment of the study vaccine. This was decided before unblinding.
Seroprotective Titers is considered as HAI antibody Titre ≥1:40; measured for each of the 3 antigens
Outcome measures
| Measure |
Vaccine Arm
n=101 Participants
Trivalent seasonal influenza vaccine
|
Placebo Arm
n=50 Participants
Phosphate buffered saline
|
|---|---|---|
|
Number and Percentage of Participants With a HAI Antibody Titer ≥1:40 (Seroprotection)
Seroprotection to H1N1 : Day 1
|
24 Participants
|
21 Participants
|
|
Number and Percentage of Participants With a HAI Antibody Titer ≥1:40 (Seroprotection)
Seroconversion to H3N2 : Day 1
|
7 Participants
|
3 Participants
|
|
Number and Percentage of Participants With a HAI Antibody Titer ≥1:40 (Seroprotection)
Seroconversion to H3N2 : Day 22
|
79 Participants
|
3 Participants
|
|
Number and Percentage of Participants With a HAI Antibody Titer ≥1:40 (Seroprotection)
Seroprotection to H1N1 : Day 22
|
96 Participants
|
22 Participants
|
|
Number and Percentage of Participants With a HAI Antibody Titer ≥1:40 (Seroprotection)
Seroprotection to B : Day 1
|
53 Participants
|
18 Participants
|
|
Number and Percentage of Participants With a HAI Antibody Titer ≥1:40 (Seroprotection)
Seroprotection to B : Day 22
|
93 Participants
|
26 Participants
|
PRIMARY outcome
Timeframe: Day 1 and Day 22Population: Per Protocol (PP) Population: Immunogenicity was assessed in a subset of 151 participants (per-protocol population) with valid post-vaccination immunogenicity measures and no major protocol violations that were determined to potentially interfere with the immunogenicity assessment of the study vaccine. This was decided before unblinding.
Serum HAI Antibodies GMTs Pre- (Day 1) and Post-vaccination (Day 22); measured for each of the 3 antigens
Outcome measures
| Measure |
Vaccine Arm
n=101 Participants
Trivalent seasonal influenza vaccine
|
Placebo Arm
n=50 Participants
Phosphate buffered saline
|
|---|---|---|
|
Geometric Mean Titers (GMTs) of Serum HAI Antibodies
GMT to H1 : Day 1
|
15.0 Titer
Interval 12.3 to 18.1
|
24.1 Titer
Interval 16.9 to 34.5
|
|
Geometric Mean Titers (GMTs) of Serum HAI Antibodies
GMT to H1 Day 22
|
336.3 Titer
Interval 268.2 to 421.7
|
25.0 Titer
Interval 17.7 to 35.2
|
|
Geometric Mean Titers (GMTs) of Serum HAI Antibodies
GMT to H3 : Day 1
|
6.9 Titer
Interval 6.0 to 7.8
|
8.0 Titer
Interval 6.4 to 10.0
|
|
Geometric Mean Titers (GMTs) of Serum HAI Antibodies
GMT to H3 : Day 22
|
88.4 Titer
Interval 65.9 to 118.5
|
8.4 Titer
Interval 6.6 to 10.5
|
|
Geometric Mean Titers (GMTs) of Serum HAI Antibodies
GMT to B : Day 1
|
27.4 Titer
Interval 21.6 to 34.8
|
21.9 Titer
Interval 15.8 to 30.3
|
|
Geometric Mean Titers (GMTs) of Serum HAI Antibodies
GMT to B : Day 22
|
103.5 Titer
Interval 86.9 to 123.3
|
36.1 Titer
Interval 26.7 to 48.7
|
PRIMARY outcome
Timeframe: Day 1 and Day 22Population: Per Protocol (PP) Population: Immunogenicity was assessed in a subset of 151 participants (per-protocol population) with valid post-vaccination immunogenicity measures and no major protocol violations that were determined to potentially interfere with the immunogenicity assessment of the study vaccine. This was decided before unblinding.
GMFR calculated as GMT for of Serum HAI Antibodies Post-vaccination/Pre-vaccination; measured for each of the 3 antigens
Outcome measures
| Measure |
Vaccine Arm
n=101 Participants
Trivalent seasonal influenza vaccine
|
Placebo Arm
n=50 Participants
Phosphate buffered saline
|
|---|---|---|
|
Geometric Mean Fold Rises (GMFRs) of Serum HAI Antibodies
GMFR for H1
|
22.5 Titer
Interval 17.5 to 28.9
|
1.0 Titer
Interval 0.9 to 1.2
|
|
Geometric Mean Fold Rises (GMFRs) of Serum HAI Antibodies
GMFR for H3
|
12.9 Titer
Interval 9.8 to 17.0
|
1.0 Titer
Interval 1.0 to 1.1
|
|
Geometric Mean Fold Rises (GMFRs) of Serum HAI Antibodies
GMFR for B
|
3.8 Titer
Interval 3.0 to 4.8
|
1.6 Titer
Interval 1.3 to 2.1
|
Adverse Events
Vaccine
Placebo
Serious adverse events
| Measure |
Vaccine
n=312 participants at risk
Trivalent seasonal influenza vaccine
|
Placebo
n=156 participants at risk
Phosphate buffered saline
|
|---|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute Lymphocytic Leukemia
|
0.32%
1/312 • Number of events 1 • 90 days
|
0.00%
0/156 • 90 days
|
|
Vascular disorders
Varicocele
|
0.32%
1/312 • Number of events 1 • 90 days
|
0.00%
0/156 • 90 days
|
Other adverse events
| Measure |
Vaccine
n=312 participants at risk
Trivalent seasonal influenza vaccine
|
Placebo
n=156 participants at risk
Phosphate buffered saline
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
0.96%
3/312 • Number of events 3 • 90 days
|
2.6%
4/156 • Number of events 4 • 90 days
|
|
Infections and infestations
Respiratory tract infection
|
2.2%
7/312 • Number of events 7 • 90 days
|
0.64%
1/156 • Number of events 1 • 90 days
|
|
Infections and infestations
Rhinitis
|
0.96%
3/312 • Number of events 3 • 90 days
|
1.9%
3/156 • Number of events 3 • 90 days
|
Additional Information
Katarina Ilic
Institute of Virology, Vaccines and Sera, Torlak
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place