Trial Outcomes & Findings for A Study of a Seasonal Trivalent Split, Inactivated Influenza Vaccine (NCT NCT02585700)

NCT ID: NCT02585700

Last Updated: 2019-01-15

Results Overview

Number of subjects with observed immediate adverse events, including allergic reaction or anaphylaxis, following administration of the study product.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

60 participants

Primary outcome timeframe

30-minute post-vaccination period.

Results posted on

2019-01-15

Participant Flow

All volunteers were recruited at the Clinical Center of Serbia, Belgrade, Serbia.

66 people were screened for the study after signing consent. 6 subjects failed screening. A total of 60 subjects received vaccine or placebo.

Participant milestones

Participant milestones
Measure
Vaccine Group
0.5 mL of influenza vaccine split, inactivated with 15 mcg of HA of B/Massachusetts, H1/A/California, and H3/A/Texas
Placebo Group
0.5 mL of phosphate buffered saline
Overall Study
STARTED
30
30
Overall Study
COMPLETED
30
30
Overall Study
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of a Seasonal Trivalent Split, Inactivated Influenza Vaccine

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Vaccine Group
n=30 Participants
0.5 mL of influenza vaccine split, inactivated with 15 mcg of HA of B/Massachusetts, H1/A/California, and H3/A/Texas
Placebo Group
n=30 Participants
0.5 mL of phosphate buffered saline
Total
n=60 Participants
Total of all reporting groups
Age, Continuous
31.00 years
STANDARD_DEVIATION 7.21 • n=5 Participants
30.70 years
STANDARD_DEVIATION 6.14 • n=7 Participants
30.85 years
STANDARD_DEVIATION 6.64 • n=5 Participants
Sex: Female, Male
Female
9 Participants
n=5 Participants
9 Participants
n=7 Participants
18 Participants
n=5 Participants
Sex: Female, Male
Male
21 Participants
n=5 Participants
21 Participants
n=7 Participants
42 Participants
n=5 Participants
Race/Ethnicity, Customized
White
30 Participants
n=5 Participants
30 Participants
n=7 Participants
60 Participants
n=5 Participants
Race/Ethnicity, Customized
Other
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Region of Enrollment
Serbia
30 participants
n=5 Participants
30 participants
n=7 Participants
60 participants
n=5 Participants

PRIMARY outcome

Timeframe: 30-minute post-vaccination period.

Population: The analysis was conducted for subjects who were randomized and received a study vaccination

Number of subjects with observed immediate adverse events, including allergic reaction or anaphylaxis, following administration of the study product.

Outcome measures

Outcome measures
Measure
Vaccine Group
n=30 Participants
0.5 mL of influenza vaccine split, inactivated with 15 mcg of HA of B/Massachusetts, H1/A/California, and H3/A/Texas
Placebo Group
n=30 Participants
0.5 mL of phosphate buffered saline
Number of Subjects With Immediate Adverse Events
0 Participants
0 Participants

PRIMARY outcome

Timeframe: 7-day period (Days 0-6) post-vaccination.

Population: The analysis was conducted for subjects who were randomized and received a study vaccination

Number of subjects reporting solicited local reactions (redness, swelling, induration, pain and tenderness) at the injection site post-vaccination with study vaccine or placebo

Outcome measures

Outcome measures
Measure
Vaccine Group
n=30 Participants
0.5 mL of influenza vaccine split, inactivated with 15 mcg of HA of B/Massachusetts, H1/A/California, and H3/A/Texas
Placebo Group
n=30 Participants
0.5 mL of phosphate buffered saline
Number and Percentage of Subjects With Solicited Local Reactogenicity
Hardness
2 Participants
0 Participants
Number and Percentage of Subjects With Solicited Local Reactogenicity
Pain
14 Participants
4 Participants
Number and Percentage of Subjects With Solicited Local Reactogenicity
Redness
6 Participants
0 Participants
Number and Percentage of Subjects With Solicited Local Reactogenicity
Swelling
2 Participants
0 Participants
Number and Percentage of Subjects With Solicited Local Reactogenicity
Tenderness
10 Participants
1 Participants

PRIMARY outcome

Timeframe: 7-day period (Days 0-6) post-vaccination.

Population: The analysis was conducted for subjects who were randomized and received a study vaccination

Number of subjects reporting solicited systemic reactions (fever, fatigue/malaise, muscle aches, joint aches, chills, nausea, vomiting, and headache) post-vaccination with study vaccine or Placebo

Outcome measures

Outcome measures
Measure
Vaccine Group
n=30 Participants
0.5 mL of influenza vaccine split, inactivated with 15 mcg of HA of B/Massachusetts, H1/A/California, and H3/A/Texas
Placebo Group
n=30 Participants
0.5 mL of phosphate buffered saline
Number and Percentage of Subjects With Solicited Systemic Reactogenicity
Temperature above 37 C
2 Participants
1 Participants
Number and Percentage of Subjects With Solicited Systemic Reactogenicity
Chills
2 Participants
0 Participants
Number and Percentage of Subjects With Solicited Systemic Reactogenicity
Headache
5 Participants
2 Participants
Number and Percentage of Subjects With Solicited Systemic Reactogenicity
Joint aches
1 Participants
2 Participants
Number and Percentage of Subjects With Solicited Systemic Reactogenicity
Muscle aches
2 Participants
1 Participants
Number and Percentage of Subjects With Solicited Systemic Reactogenicity
Nausea
2 Participants
0 Participants
Number and Percentage of Subjects With Solicited Systemic Reactogenicity
Tiredness
5 Participants
0 Participants
Number and Percentage of Subjects With Solicited Systemic Reactogenicity
Vomiting
1 Participants
0 Participants

PRIMARY outcome

Timeframe: Within 21 days post vaccination

Population: The analysis was conducted for subjects who were randomized and received a study vaccination

These data are presented broadly as number per group for the study. Please see AE reporting section for more specific details on AEs.

Outcome measures

Outcome measures
Measure
Vaccine Group
n=30 Participants
0.5 mL of influenza vaccine split, inactivated with 15 mcg of HA of B/Massachusetts, H1/A/California, and H3/A/Texas
Placebo Group
n=30 Participants
0.5 mL of phosphate buffered saline
Number and Percentage of Subjects With Occurrence of Unsolicited Adverse Events
2 Participants
4 Participants

PRIMARY outcome

Timeframe: Over the entire study period (Day 90).

Population: The analysis was conducted for subjects who were randomized and received a study vaccination

Outcome measures

Outcome measures
Measure
Vaccine Group
n=30 Participants
0.5 mL of influenza vaccine split, inactivated with 15 mcg of HA of B/Massachusetts, H1/A/California, and H3/A/Texas
Placebo Group
n=30 Participants
0.5 mL of phosphate buffered saline
Number and Percentage of Subjects With Occurrence of Serious Adverse Events (SAE)
Serious adverse events (SAEs)--related
0 Participants
0 Participants
Number and Percentage of Subjects With Occurrence of Serious Adverse Events (SAE)
SAEs--not related
0 Participants
0 Participants

SECONDARY outcome

Timeframe: Day 21

Population: The analysis was conducted for subjects who were randomized and received a study vaccination

Seroconversion is defined as a serum HAI titer meeting the following criteria: * pre-vaccination titer \<1:10 and a post-vaccination titer ≥ 1:40 or * pre-vaccination titer ≥ 1:10 and at least a four-fold increase in post-vaccination measured on Day 21. The 3 influenza strains assessed were B/Massachusetts, H1/A/California and H3/A/Texas

Outcome measures

Outcome measures
Measure
Vaccine Group
n=30 Participants
0.5 mL of influenza vaccine split, inactivated with 15 mcg of HA of B/Massachusetts, H1/A/California, and H3/A/Texas
Placebo Group
n=30 Participants
0.5 mL of phosphate buffered saline
Number and Percentage of Seroconverted Subjects Against 3 Strains of Influenza Vaccine.
Seroconversion to H1
25 Participants
0 Participants
Number and Percentage of Seroconverted Subjects Against 3 Strains of Influenza Vaccine.
Seroconversion to H3
23 Participants
0 Participants
Number and Percentage of Seroconverted Subjects Against 3 Strains of Influenza Vaccine.
Seroconversion to B
21 Participants
0 Participants

SECONDARY outcome

Timeframe: Day 0 and Day 21 post vaccination

Population: All vaccinated subjects who have valid post vaccination immunogenicity measures with no major protocol violations

A seroprotected subject was defined as a vaccinated subject who had a serum Hemagluttination Inhibition (HAI) titer ≥ 1:40. The 3 influenza strains assessed were B/Massachusetts, H1/A/California an d H3/A/Texas

Outcome measures

Outcome measures
Measure
Vaccine Group
n=30 Participants
0.5 mL of influenza vaccine split, inactivated with 15 mcg of HA of B/Massachusetts, H1/A/California, and H3/A/Texas
Placebo Group
n=30 Participants
0.5 mL of phosphate buffered saline
Number and Percentage of Seroprotected Subjects Against 3 Strains of Influenza Vaccine
H1
30 Participants
10 Participants
Number and Percentage of Seroprotected Subjects Against 3 Strains of Influenza Vaccine
H3
30 Participants
19 Participants
Number and Percentage of Seroprotected Subjects Against 3 Strains of Influenza Vaccine
B
26 Participants
5 Participants

SECONDARY outcome

Timeframe: Pre- (Day 0) and post-vaccination (Day 21)

Population: All vaccinated subjects with no major protocol violations who have valid post vaccination immunogenicity measures

The 3 influenza strains assessed were B/Massachusetts, H1/A/California an d H3/A/Texas

Outcome measures

Outcome measures
Measure
Vaccine Group
n=30 Participants
0.5 mL of influenza vaccine split, inactivated with 15 mcg of HA of B/Massachusetts, H1/A/California, and H3/A/Texas
Placebo Group
n=30 Participants
0.5 mL of phosphate buffered saline
Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Antibodies Pre- (Day 0) and Post-vaccination (Day 21) for Each of the 3 Antigens
GMT to H1 Day 0
15.97 Titers
Interval 11.3 to 23.1
21.19 Titers
Interval 14.82 to 30.29
Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Antibodies Pre- (Day 0) and Post-vaccination (Day 21) for Each of the 3 Antigens
GMT to H1 Day 21
295.14 Titers
Interval 240.1 to 362.8
22.32 Titers
Interval 15.72 to 31.69
Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Antibodies Pre- (Day 0) and Post-vaccination (Day 21) for Each of the 3 Antigens
GMT to H3 Day 0
37.75 Titers
Interval 25.88 to 55.07
41.41 Titers
Interval 28.02 to 61.2
Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Antibodies Pre- (Day 0) and Post-vaccination (Day 21) for Each of the 3 Antigens
GMT to H3 Day 21
439.67 Titers
Interval 320.54 to 603.06
42.87 Titers
Interval 28.92 to 63.55
Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Antibodies Pre- (Day 0) and Post-vaccination (Day 21) for Each of the 3 Antigens
GMT to B Day 0
10.47 Titers
Interval 7.91 to 13.86
10.72 Titers
Interval 7.72 to 14.89
Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Antibodies Pre- (Day 0) and Post-vaccination (Day 21) for Each of the 3 Antigens
GMT to B Day 21
75.95 Titers
Interval 56.88 to 101.4
10.66 Titers
Interval 7.69 to 14.76

SECONDARY outcome

Timeframe: Pre- (Day 0) and post-vaccination (Day 21)

Population: All vaccinated subjects who have valid post vaccination immunogenicity measures with no major protocol violations

The 3 influenza strains assessed were B/Massachusetts, H1/A/California an d H3/A/Texas

Outcome measures

Outcome measures
Measure
Vaccine Group
n=30 Participants
0.5 mL of influenza vaccine split, inactivated with 15 mcg of HA of B/Massachusetts, H1/A/California, and H3/A/Texas
Placebo Group
n=30 Participants
0.5 mL of phosphate buffered saline
Geometric Mean Fold Rises (GMFRs) of Serum (HAI) Antibodies (Post-vaccination / Pre-vaccination) for Each of the 3 Antigens.
GMFR for H1
18.49 fold rise
Interval 12.22 to 27.95
1.05 fold rise
Interval 1.0 to 1.11
Geometric Mean Fold Rises (GMFRs) of Serum (HAI) Antibodies (Post-vaccination / Pre-vaccination) for Each of the 3 Antigens.
GMFR for H3
11.65 fold rise
Interval 7.82 to 17.35
1.04 fold rise
Interval 0.99 to 1.08
Geometric Mean Fold Rises (GMFRs) of Serum (HAI) Antibodies (Post-vaccination / Pre-vaccination) for Each of the 3 Antigens.
GMFR for B
7.25 fold rise
Interval 5.53 to 9.52
0.99 fold rise
Interval 0.96 to 1.03

SECONDARY outcome

Timeframe: Pre- (Day 0) and post-vaccination (Day 21)

Population: All vaccinated subjects who have valid post vaccination immunogenicity measures with no major protocol violations

Outcome measures

Outcome measures
Measure
Vaccine Group
n=30 Participants
0.5 mL of influenza vaccine split, inactivated with 15 mcg of HA of B/Massachusetts, H1/A/California, and H3/A/Texas
Placebo Group
n=30 Participants
0.5 mL of phosphate buffered saline
Geometric Mean Neutralization Titers of Neutralizing Antibodies (MNT) Pre- (Day 0) and Post-vaccination (Day 21) for Each of the 3 Antigens.
GMT to H1 Day 0
24.06 Titers
Interval 18.61 to 31.11
31.75 Titers
Interval 24.06 to 41.89
Geometric Mean Neutralization Titers of Neutralizing Antibodies (MNT) Pre- (Day 0) and Post-vaccination (Day 21) for Each of the 3 Antigens.
GMT to H1 Day 21
211.12 Titers
Interval 164.95 to 270.22
40.00 Titers
Interval 30.47 to 52.52
Geometric Mean Neutralization Titers of Neutralizing Antibodies (MNT) Pre- (Day 0) and Post-vaccination (Day 21) for Each of the 3 Antigens.
GMT to H3 Day 0
18.02 Titers
Interval 12.74 to 25.51
19.77 Titers
Interval 15.11 to 25.86
Geometric Mean Neutralization Titers of Neutralizing Antibodies (MNT) Pre- (Day 0) and Post-vaccination (Day 21) for Each of the 3 Antigens.
GMT to H3 Day 21
125.53 Titers
Interval 87.82 to 179.45
24.34 Titers
Interval 18.39 to 32.22
Geometric Mean Neutralization Titers of Neutralizing Antibodies (MNT) Pre- (Day 0) and Post-vaccination (Day 21) for Each of the 3 Antigens.
GMT to B Day 0
80.93 Titers
Interval 59.21 to 110.61
70.45 Titers
Interval 48.06 to 103.28
Geometric Mean Neutralization Titers of Neutralizing Antibodies (MNT) Pre- (Day 0) and Post-vaccination (Day 21) for Each of the 3 Antigens.
GMT to B Day 21
331.28 Titers
Interval 278.78 to 393.68
105.56 Titers
Interval 75.73 to 147.15

SECONDARY outcome

Timeframe: Pre- (Day 0) and post-vaccination (Day 21)

Population: All vaccinated subjects who have valid post vaccination immunogenicity measures with no major protocol violations

The 3 influenza strains assessed were B/Massachusetts, H1/A/California an d H3/A/Texas

Outcome measures

Outcome measures
Measure
Vaccine Group
n=30 Participants
0.5 mL of influenza vaccine split, inactivated with 15 mcg of HA of B/Massachusetts, H1/A/California, and H3/A/Texas
Placebo Group
n=30 Participants
0.5 mL of phosphate buffered saline
Geometric Mean Fold Rises (GMFRs) of MNT (Post-vaccination / Pre-vaccination) for Each of the 3 Antigens.
GMFR for H1
8.77 fold rise
Interval 6.7 to 11.49
1.26 fold rise
Interval 1.09 to 1.45
Geometric Mean Fold Rises (GMFRs) of MNT (Post-vaccination / Pre-vaccination) for Each of the 3 Antigens.
GMFR for H3
6.96 fold rise
Interval 4.89 to 9.92
1.23 fold rise
Interval 1.14 to 1.33
Geometric Mean Fold Rises (GMFRs) of MNT (Post-vaccination / Pre-vaccination) for Each of the 3 Antigens.
GMFR for B
4.09 fold rise
Interval 3.11 to 5.38
1.50 fold rise
Interval 1.18 to 1.89

Adverse Events

Vaccine Group

Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths

Placebo Group

Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Vaccine Group
n=30 participants at risk
0.5 mL of influenza vaccine, split, inactivated with 15 mcg of HA of each of 3 strains: * NYMC BX-51B reassortant of B/Massachusetts/2/2012 * X-181 reassortant of H1/A/California/7/2009 * X-223A reassortant of H3/A/Texas/50/2012.
Placebo Group
n=30 participants at risk
0.5 mL of phosphate buffered saline
Respiratory, thoracic and mediastinal disorders
Respiratory Tract Infection
3.3%
1/30 • 90 days
0.00%
0/30 • 90 days
Gastrointestinal disorders
Diarrhea
0.00%
0/30 • 90 days
3.3%
1/30 • 90 days
Investigations
Alanine Aminotransferase Increased
0.00%
0/30 • 90 days
3.3%
1/30 • 90 days
Musculoskeletal and connective tissue disorders
Back Pain
3.3%
1/30 • 90 days
3.3%
1/30 • 90 days
Respiratory, thoracic and mediastinal disorders
Cough
0.00%
0/30 • 90 days
3.3%
1/30 • 90 days

Additional Information

Dr. Goran Stevanovic

Clinical Center of Serbia-Clinic for Infectious and Tropical Diseases

Phone: +381 64 1703059

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place