Trial Outcomes & Findings for Safety and Immunogenicity of Fluzone® Quadrivalent Vaccine Administered to Healthy Children (NCT NCT02915302)
NCT ID: NCT02915302
Last Updated: 2022-03-29
Results Overview
Fever rate was defined as percentage of participants with fever (temperature \>=100.4 degrees Fahrenheit \[38.0 degrees Celsius\]) following vaccination with Fluzone Quadrivalent vaccine.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
1950 participants
Primary outcome timeframe
Within 7 days after any vaccination
Results posted on
2022-03-29
Participant Flow
Study participants were enrolled in 38 centers in the United States from 23 September 2016 to 02 January 2017.
A total of 1950 participants were randomized in the study.
Participant milestones
| Measure |
Fluzone Quadrivalent Vaccine, 0.25-mL
Participants received a 0.25-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended per Advisory Committee on Immunization Practices (ACIP) guidance, a second 0.25-mL dose of Fluzone Quadrivalent vaccine was administered at Day 28.
|
Fluzone Quadrivalent Vaccine, 0.5-mL
Participants received a 0.5-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended per ACIP guidance, a second 0.5-mL dose of Fluzone Quadrivalent vaccine was administered at Day 28.
|
|---|---|---|
|
Overall Study
STARTED
|
955
|
995
|
|
Overall Study
Vaccinated (Safety Analysis Set)
|
949
|
992
|
|
Overall Study
COMPLETED
|
890
|
917
|
|
Overall Study
NOT COMPLETED
|
65
|
78
|
Reasons for withdrawal
| Measure |
Fluzone Quadrivalent Vaccine, 0.25-mL
Participants received a 0.25-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended per Advisory Committee on Immunization Practices (ACIP) guidance, a second 0.25-mL dose of Fluzone Quadrivalent vaccine was administered at Day 28.
|
Fluzone Quadrivalent Vaccine, 0.5-mL
Participants received a 0.5-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended per ACIP guidance, a second 0.5-mL dose of Fluzone Quadrivalent vaccine was administered at Day 28.
|
|---|---|---|
|
Overall Study
Adverse Event
|
3
|
0
|
|
Overall Study
Protocol Violation
|
20
|
27
|
|
Overall Study
Lost to Follow-up
|
19
|
22
|
|
Overall Study
Withdrawal by Subject
|
22
|
29
|
|
Overall Study
Other
|
1
|
0
|
Baseline Characteristics
Safety and Immunogenicity of Fluzone® Quadrivalent Vaccine Administered to Healthy Children
Baseline characteristics by cohort
| Measure |
Fluzone Quadrivalent Vaccine, 0.25-mL
n=949 Participants
Participants received a 0.25-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended per ACIP guidance, a second 0.25-mL dose of Fluzone Quadrivalent vaccine was administered at Day 28.
|
Fluzone Quadrivalent Vaccine, 0.5-mL
n=992 Participants
Participants received a 0.5-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended per ACIP guidance, a second 0.5-mL dose of Fluzone Quadrivalent vaccine was administered at Day 28.
|
Total
n=1941 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
20.4 Months
STANDARD_DEVIATION 8.75 • n=99 Participants
|
20.5 Months
STANDARD_DEVIATION 8.55 • n=107 Participants
|
20.5 Months
STANDARD_DEVIATION 8.65 • n=206 Participants
|
|
Sex: Female, Male
Female
|
469 Participants
n=99 Participants
|
495 Participants
n=107 Participants
|
964 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
480 Participants
n=99 Participants
|
497 Participants
n=107 Participants
|
977 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
206 Participants
n=99 Participants
|
221 Participants
n=107 Participants
|
427 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
731 Participants
n=99 Participants
|
763 Participants
n=107 Participants
|
1494 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
12 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
20 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
9 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
19 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
9 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
4 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
9 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
178 Participants
n=99 Participants
|
195 Participants
n=107 Participants
|
373 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
717 Participants
n=99 Participants
|
725 Participants
n=107 Participants
|
1442 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
36 Participants
n=99 Participants
|
43 Participants
n=107 Participants
|
79 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
949 participants
n=99 Participants
|
992 participants
n=107 Participants
|
1941 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Within 7 days after any vaccinationPopulation: Analysis was performed using the safety analysis set. Here, 'Number of participants analyzed' = those participants with available data for this endpoint.
Fever rate was defined as percentage of participants with fever (temperature \>=100.4 degrees Fahrenheit \[38.0 degrees Celsius\]) following vaccination with Fluzone Quadrivalent vaccine.
Outcome measures
| Measure |
Fluzone Quadrivalent Vaccine, 0.25-mL
n=893 Participants
Participants received a 0.25-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended per ACIP guidance, a second 0.25-mL dose of Fluzone Quadrivalent vaccine was administered at Day 28.
|
Fluzone Quadrivalent Vaccine, 0.5-mL
n=930 Participants
Participants received a 0.5-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended per ACIP guidance, a second 0.5-mL dose of Fluzone Quadrivalent vaccine was administered at Day 28.
|
|---|---|---|
|
Percentage of Participants With Fever (Fever Rate) Following Vaccination With Fluzone Quadrivalent Vaccine
|
11.31 percentage of participants
Interval 9.31 to 13.57
|
12.15 percentage of participants
Interval 10.12 to 14.42
|
SECONDARY outcome
Timeframe: 28 days post-final vaccinationPopulation: Analysis was performed using Per-protocol (PP) analysis set which included participants who received at least 1 dose of study vaccine and had a valid post-vaccination serologic result for at least 1 strain without any protocol deviations. Here, 'Number Analyzed' = those participants with available data for specified categories.
Anti-influenza antibodies were measured using a hemagglutination inhibition (HAI) assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, B Yamagata lineage.
Outcome measures
| Measure |
Fluzone Quadrivalent Vaccine, 0.25-mL
n=525 Participants
Participants received a 0.25-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended per ACIP guidance, a second 0.25-mL dose of Fluzone Quadrivalent vaccine was administered at Day 28.
|
Fluzone Quadrivalent Vaccine, 0.5-mL
n=543 Participants
Participants received a 0.5-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended per ACIP guidance, a second 0.5-mL dose of Fluzone Quadrivalent vaccine was administered at Day 28.
|
|---|---|---|
|
Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies
A/H3N2
|
221 Titers (1/dilutions [dil])
Interval 191.0 to 256.0
|
332 Titers (1/dilutions [dil])
Interval 290.0 to 380.0
|
|
Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies
A/H1N1
|
214 Titers (1/dilutions [dil])
Interval 185.0 to 247.0
|
310 Titers (1/dilutions [dil])
Interval 271.0 to 354.0
|
|
Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies
B Victoria
|
261 Titers (1/dilutions [dil])
Interval 227.0 to 299.0
|
348 Titers (1/dilutions [dil])
Interval 304.0 to 398.0
|
|
Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies
B Yamagata
|
243 Titers (1/dilutions [dil])
Interval 213.0 to 277.0
|
349 Titers (1/dilutions [dil])
Interval 307.0 to 397.0
|
SECONDARY outcome
Timeframe: 28 days post-final vaccinationPopulation: Analysis was performed using the PP analysis set. Here, 'Number Analyzed' = those participants with available data for specified categories.
Anti-influenza antibodies were measured using HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, B Yamagata lineage. SCR was defined as percentage of participants with either a pre-vaccination titer \<10 (1/dil) and a post-final vaccination titer \>=40 (1/dil), or a pre-vaccination titer \>=10 (1/dil) and at least a four-fold increase in post-final vaccination titer.
Outcome measures
| Measure |
Fluzone Quadrivalent Vaccine, 0.25-mL
n=525 Participants
Participants received a 0.25-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended per ACIP guidance, a second 0.25-mL dose of Fluzone Quadrivalent vaccine was administered at Day 28.
|
Fluzone Quadrivalent Vaccine, 0.5-mL
n=543 Participants
Participants received a 0.5-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended per ACIP guidance, a second 0.5-mL dose of Fluzone Quadrivalent vaccine was administered at Day 28.
|
|---|---|---|
|
Percentage of Participants With Seroconversion (Seroconversion Rate [SCR]) to Influenza Vaccine Antigens
A/H1N1
|
78.9 percentage of participants
Interval 75.0 to 82.5
|
84.1 percentage of participants
Interval 80.5 to 87.2
|
|
Percentage of Participants With Seroconversion (Seroconversion Rate [SCR]) to Influenza Vaccine Antigens
A/H3N2
|
81.9 percentage of participants
Interval 78.1 to 85.3
|
86.2 percentage of participants
Interval 82.9 to 89.2
|
|
Percentage of Participants With Seroconversion (Seroconversion Rate [SCR]) to Influenza Vaccine Antigens
B Victoria
|
87.2 percentage of participants
Interval 83.9 to 90.1
|
88.6 percentage of participants
Interval 85.4 to 91.3
|
|
Percentage of Participants With Seroconversion (Seroconversion Rate [SCR]) to Influenza Vaccine Antigens
B Yamagata
|
87.8 percentage of participants
Interval 84.5 to 90.6
|
91.2 percentage of participants
Interval 88.3 to 93.5
|
Adverse Events
Fluzone Quadrivalent Vaccine, 0.25-mL
Serious events: 5 serious events
Other events: 698 other events
Deaths: 0 deaths
Fluzone Quadrivalent Vaccine, 0.5-mL
Serious events: 5 serious events
Other events: 737 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Fluzone Quadrivalent Vaccine, 0.25-mL
n=949 participants at risk
Participants received a 0.25-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended per ACIP guidance, a second 0.25-mL dose of Fluzone Quadrivalent vaccine was administered at Day 28.
|
Fluzone Quadrivalent Vaccine, 0.5-mL
n=992 participants at risk
Participants received a 0.5-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended per ACIP guidance, a second 0.5-mL dose of Fluzone Quadrivalent vaccine was administered at Day 28.
|
|---|---|---|
|
Infections and infestations
Cellulitis
|
0.00%
0/949 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
0.10%
1/992 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
|
Infections and infestations
Pneumonia
|
0.11%
1/949 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
0.10%
1/992 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
|
Infections and infestations
Respiratory syncytial virus bronchiolitis
|
0.00%
0/949 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
0.10%
1/992 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
|
Infections and infestations
Tonsillitis
|
0.11%
1/949 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
0.00%
0/992 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.11%
1/949 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
0.00%
0/992 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
|
Injury, poisoning and procedural complications
Accidental exposure to product by child
|
0.00%
0/949 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
0.10%
1/992 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/949 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
0.10%
1/992 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial hyperreactivity
|
0.11%
1/949 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
0.00%
0/992 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
|
Skin and subcutaneous tissue disorders
Urticaria chronic
|
0.11%
1/949 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
0.00%
0/992 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
Other adverse events
| Measure |
Fluzone Quadrivalent Vaccine, 0.25-mL
n=949 participants at risk
Participants received a 0.25-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended per ACIP guidance, a second 0.25-mL dose of Fluzone Quadrivalent vaccine was administered at Day 28.
|
Fluzone Quadrivalent Vaccine, 0.5-mL
n=992 participants at risk
Participants received a 0.5-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended per ACIP guidance, a second 0.5-mL dose of Fluzone Quadrivalent vaccine was administered at Day 28.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
5.7%
54/949 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
5.8%
58/992 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
|
Gastrointestinal disorders
Vomiting
|
12.1%
115/949 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
11.0%
109/992 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
|
General disorders
Crying
|
31.8%
302/949 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
32.4%
321/992 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
|
General disorders
Injection site erythema
|
22.1%
210/949 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
23.0%
228/992 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
|
General disorders
Injection site pain
|
45.3%
430/949 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
47.7%
473/992 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
|
General disorders
Injection site swelling
|
12.3%
117/949 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
13.9%
138/992 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
|
General disorders
Pyrexia
|
15.9%
151/949 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
16.5%
164/992 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
|
Infections and infestations
Upper respiratory tract infection
|
7.3%
69/949 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
7.1%
70/992 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
26.2%
249/949 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
26.9%
267/992 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
|
Nervous system disorders
Somnolence
|
30.8%
292/949 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
29.6%
294/992 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
|
Psychiatric disorders
Irritability
|
45.4%
431/949 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
46.2%
458/992 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
11.5%
109/949 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
10.8%
107/992 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
7.8%
74/949 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
7.5%
74/992 • Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 28 post-final vaccination.
All AEs were presented.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Sponsor must have the opportunity to review at least 60 days prior to submission for publication or presentation. If review indicates that potentially patentable subject matter would be disclosed, publication or public disclosure may be delayed for a maximum of an additional 60 days to allow for filing the necessary patent applications.
- Publication restrictions are in place
Restriction type: OTHER