Trial Outcomes & Findings for Study of Quadrivalent Influenza Vaccine Among Children (NCT NCT01240746)

Last Updated: 2015-07-14

Results Overview

Immunogenicity outcomes were assessed in serum samples by hemagglutination inhibition (HAI) assay. The lower limit of quantitation (LLOQ) was set at the lowest dilution used in the assay, 1/10. Titers below this level were reported as \<10.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

4363 participants

Primary outcome timeframe

Day 28 post final vaccination

Results posted on

2015-07-14

Participant Flow

The study participants were enrolled from 11 November 2010 to 20 June 2011 in 69 clinical centers in the US

A total of 4363 participants who met all the inclusion criteria and none of the exclusion criteria were enrolled, randomized and vaccinated in the study.

Participant milestones

Participant milestones
Measure	Study Group 1 (2010-2011 Trivalent Influenza Vaccine) Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen.	Study Group 2 (Investigational Trivalent Influenza Vaccine) Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Study Group 3 (Investigational Quadrivalent Influenza Vaccine) Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Overall Study STARTED	736	725	2902
Overall Study COMPLETED	677	677	2659
Overall Study NOT COMPLETED	59	48	243

Reasons for withdrawal

Reasons for withdrawal
Measure	Study Group 1 (2010-2011 Trivalent Influenza Vaccine) Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen.	Study Group 2 (Investigational Trivalent Influenza Vaccine) Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Study Group 3 (Investigational Quadrivalent Influenza Vaccine) Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Overall Study Adverse Event	2	0	10
Overall Study Lost to Follow-up	23	20	102
Overall Study Protocol Violation	24	15	72
Overall Study Withdrawal by Subject	10	13	59

Baseline Characteristics

Study of Quadrivalent Influenza Vaccine Among Children

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Study Group 1 (Trivalent Influenza Vaccine) n=736 Participants Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Study Group 2 (Investigational Trivalent Influenza Vaccine) n=725 Participants Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Study Group 3 (Investigational Quadrivalent Influenza Vaccine) n=2902 Participants Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)	Total n=4363 Participants Total of all reporting groups
Age, Categorical <=18 years	736 Participants n=5 Participants	725 Participants n=7 Participants	2902 Participants n=5 Participants	4363 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	49.6 Months STANDARD_DEVIATION 29.0 • n=5 Participants	49.6 Months STANDARD_DEVIATION 28.7 • n=7 Participants	49.8 Months STANDARD_DEVIATION 29.7 • n=5 Participants	49.8 Months STANDARD_DEVIATION 29.4 • n=4 Participants
Sex: Female, Male Female	367 Participants n=5 Participants	359 Participants n=7 Participants	1427 Participants n=5 Participants	2153 Participants n=4 Participants
Sex: Female, Male Male	369 Participants n=5 Participants	366 Participants n=7 Participants	1475 Participants n=5 Participants	2210 Participants n=4 Participants
Region of Enrollment United States	736 Participants n=5 Participants	725 Participants n=7 Participants	2902 Participants n=5 Participants	4363 Participants n=4 Participants

PRIMARY outcome

Timeframe: Day 28 post final vaccination

Population: Geometric mean titers (GMT) to influenza vaccine A antigens were determined in randomized and vaccinated participants, per-protocol population. The GMT data for antigen A/Victoria/210/2009 and A/California/07/2009 were pooled for participants vaccinated with either 2010-2011 TIV or the investigational TIV. Data presented in column for Group 1.

Outcome measures

Outcome measures
Measure	Study Group 1 (Trivalent Influenza Vaccine) n=1461 Participants Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Study Group 2 (Investigational Trivalent Influenza Vaccine) Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Study Group 3 (Investigational Quadrivalent Influenza Vaccine) n=2339 Participants Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Geometric Mean Titers Against Influenza A Strains After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants A/California/07/2009 (A/H1N1) [N = 1461, 0, 2339]	1096 Titers Interval 1008.0 to 1192.0	—	1124 Titers Interval 1060.0 to 1192.0
Geometric Mean Titers Against Influenza A Strains After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants A/Victoria/210/2009 (A/H3N2) [N = 1461, 0, 2339	828 Titers Interval 774.0 to 887.0	—	822 Titers Interval 783.0 to 862.0

PRIMARY outcome

Timeframe: Day 28 post final vaccination

Population: Geometric mean titers to influenza vaccine B antigens were determined in randomized and vaccinated participants, per-protocol population. Data presented for participants with valid serology results for the B antigen.

Outcome measures

Outcome measures
Measure	Study Group 1 (Trivalent Influenza Vaccine) n=582 Participants Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Study Group 2 (Investigational Trivalent Influenza Vaccine) n=599 Participants Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Study Group 3 (Investigational Quadrivalent Influenza Vaccine) n=2339 Participants Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Geometric Mean Titers Against Influenza B Strains After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines With Corresponding B Strain in All Participants B/Brisbane/60/2008 (581, 0, 2238)	64.3 Titers Interval 58.3 to 70.9	NA Titers B/Brisbane/60/2008 antigen was not in the influenza vaccine administered to this group.	86.1 Titers Interval 81.8 to 90.6
Geometric Mean Titers Against Influenza B Strains After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines With Corresponding B Strain in All Participants B/Florida/04/2006 (0, 598, 2338)	NA Titers B/Florida/04/2006 antigen was not in the influenza vaccine administered to this group.	58.3 Titers Interval 52.6 to 64.7	61.5 Titers Interval 58.6 to 64.7

PRIMARY outcome

Timeframe: Day 28 post final vaccination

Population: Geometric mean titers to influenza vaccine B antigens (cross-reactive antibody) were determined in randomized and vaccinated participants, per-protocol population. Data presented for participants with valid serology results for the B antigen.

Outcome measures

Outcome measures
Measure	Study Group 1 (Trivalent Influenza Vaccine) n=582 Participants Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Study Group 2 (Investigational Trivalent Influenza Vaccine) n=599 Participants Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Study Group 3 (Investigational Quadrivalent Influenza Vaccine) n=2339 Participants Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Geometric Mean Titers Against Influenza B Strains After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines Without Corresponding B Strain in All Participants B/Brisbane/60/2008 (0, 599, 2338)	NA Titers B/Florida/04/2006 antigen was not in the influenza vaccine administered to this group.	19.5 Titers Interval 17.4 to 21.8	86.1 Titers Interval 81.8 to 90.6
Geometric Mean Titers Against Influenza B Strains After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines Without Corresponding B Strain in All Participants B/Florida/04/2006 (581, 0, 2338)	16.3 Titers Interval 14.8 to 17.9	NA Titers B/Brisbane/60/2008 antigen was not in the influenza vaccine administered to this group.	61.5 Titers Interval 58.6 to 64.7

PRIMARY outcome

Timeframe: Day 28 post final vaccination

Population: Geometric mean titers to influenza vaccine antigens were determined in randomized and vaccinated participants, per-protocol population. Data presented for participants aged 6 months to less than 36 months with valid serology results for the particular antigen.

Outcome measures

Outcome measures
Measure	Study Group 1 (Trivalent Influenza Vaccine) n=225 Participants Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Study Group 2 (Investigational Trivalent Influenza Vaccine) n=245 Participants Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Study Group 3 (Investigational Quadrivalent Influenza Vaccine) n=949 Participants Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Geometric Mean Titers Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 6 Months to Less Than 36 Months. A/H1N1, Pre-vaccination (224, 245, 943)	25.6 Titers Interval 19.4 to 33.7	31.3 Titers Interval 23.8 to 41.1	25.7 Titers Interval 22.4 to 29.5
Geometric Mean Titers Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 6 Months to Less Than 36 Months. A/H1N1, Post-vaccination (224, 243, 947)	797 Titers Interval 664.0 to 957.0	645 Titers Interval 530.0 to 784.0	747 Titers Interval 680.0 to 821.0
Geometric Mean Titers Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 6 Months to Less Than 36 Months. A/H3N2, Pre-vaccination (224, 245, 945)	9.52 Titers Interval 7.9 to 11.5	10.1 Titers Interval 8.26 to 12.3	9.19 Titers Interval 8.42 to 10.0
Geometric Mean Titers Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 6 Months to Less Than 36 Months. A/H3N2, Post-vaccination (224, 243, 944)	558 Titers Interval 483.0 to 646.0	583 Titers Interval 507.0 to 671.0	526 Titers Interval 492.0 to 562.0
Geometric Mean Titers Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 6 Months to Less Than 36 Months. B/Brisbane, Pre-vaccination (225, 245, 947)	6.56 Titers Interval 5.92 to 7.27	6.62 Titers Interval 6.0 to 7.3	6.41 Titers Interval 6.1 to 6.73
Geometric Mean Titers Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 6 Months to Less Than 36 Months. B/Brisbane, Post-vaccination (225, 245, 948)	54.7 Titers Interval 47.2 to 63.4	12.0 Titers Interval 10.3 to 13.9	72.8 Titers Interval 67.3 to 78.7
Geometric Mean Titers Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 6 Months to Less Than 36 Months. B/Florida, Pre-vaccination (225, 245, 946)	5.33 Titers Interval 5.1 to 5.56	5.26 Titers Interval 5.09 to 5.44	5.34 Titers Interval 5.23 to 5.46
Geometric Mean Titers Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 6 Months to Less Than 36 Months. B/Florida, Post-vaccination (225, 245, 948)	8.56 Titers Interval 7.68 to 9.54	32.9 Titers Interval 28.7 to 37.6	36.2 Titers Interval 33.7 to 38.8

PRIMARY outcome

Timeframe: Day 28 post-vaccination

Population: Geometric mean titers to influenza vaccine antigens were determined in randomized and vaccinated participants, per-protocol population. Data presented for participants aged 3 years to less than 9 Years with valid serology results for the particular antigen.

Outcome measures

Outcome measures
Measure	Study Group 1 (Trivalent Influenza Vaccine) n=357 Participants Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Study Group 2 (Investigational Trivalent Influenza Vaccine) n=354 Participants Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Study Group 3 (Investigational Quadrivalent Influenza Vaccine) n=1390 Participants Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Geometric Mean Titers Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 3 Years to Less Than 9 Years. A/H1N1, Post-vaccination (357, 354, 1390)	1565 Titers Interval 1355.0 to 1807.0	1348 Titers Interval 1166.0 to 1559.0	1484 Titers Interval 1380.0 to 1595.0
Geometric Mean Titers Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 3 Years to Less Than 9 Years. A/H3N2, Pre-vaccination (355, 353, 1389)	70.6 Titers Interval 57.3 to 87.0	64.1 Titers Interval 51.9 to 79.2	63.9 Titers Interval 57.6 to 70.8
Geometric Mean Titers Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 3 Years to Less Than 9 Years. A/H3N2, Post-vaccination (356, 353, 1390)	924 Titers Interval 816.0 to 1046.0	1214 Titers Interval 1078.0 to 1367.0	1112 Titers Interval 1046.0 to 1183.0
Geometric Mean Titers Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 3 Years to Less Than 9 Years. B/Brisbane, Pre-vaccination (357, 354, 1390)	10.1 Titers Interval 9.05 to 11.2	10.6 Titers Interval 9.52 to 11.9	9.73 Titers Interval 9.23 to 10.3
Geometric Mean Titers Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 3 Years to Less Than 9 Years. B/Brisbane, Post-vaccination (356, 354, 1390)	71.2 Titers Interval 62.6 to 81.1	27.3 Titers Interval 23.4 to 31.8	96.6 Titers Interval 90.3 to 103.0
Geometric Mean Titers Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 3 Years to Less Than 9 Years. A/H1N1, Pre-vaccination (357, 354, 1390)	53.5 Titers Interval 43.9 to 65.2	54.4 Titers Interval 44.4 to 66.8	54.9 Titers Interval 49.6 to 60.7
Geometric Mean Titers Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 3 Years to Less Than 9 Years. B/Florida, Pre-vaccination (357, 353, 1390)	9.09 Titers Interval 8.26 to 10.0	9.84 Titers Interval 8.91 to 10.9	9.34 Titers Interval 8.89 to 9.82
Geometric Mean Titers Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 3 Years to Less Than 9 Years. B/Florida, Post-vaccination (356, 353, 1390)	24.4 Titers Interval 21.6 to 27.5	86.9 Titers Interval 76.1 to 99.2	88.5 Titers Interval 83.1 to 94.1

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 28 post final vaccination

Population: Seroconversion with respect to influenza vaccine B antigens were determined in randomized and vaccinated participants, per-protocol population

Immunogenicity outcomes were assessed in serum samples by HAI assay. The lower limit of quantitation (LLOQ) was set at the lowest dilution used in the assay, 1/10. Titers below this level were reported as \<10. Seroconversion was defined as either a pre-vaccination HAI titer \<1:10 and a post-vaccination titer ≥1:40 or a pre-vaccination titer ≥1:10 and ≥four-fold increase in post-vaccination

Outcome measures

Outcome measures
Measure	Study Group 1 (Trivalent Influenza Vaccine) n=582 Participants Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Study Group 2 (Investigational Trivalent Influenza Vaccine) n=599 Participants Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Study Group 3 (Investigational Quadrivalent Influenza Vaccine) n=2339 Participants Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Seroconversion Against Influenza B Strains After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines With Corresponding B Strain in All Participants B/Brisbane/60/2008 (581, 0, 2336)	355 Participants	NA Participants Interval 0.0 to 0.0 B/Brisbane/60/2008 antigen was not in the influenza vaccine administered to this group.	1677 Participants Interval 0.0 to 0.0
Seroconversion Against Influenza B Strains After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines With Corresponding B Strain in All Participants B/Florida/04/2006 (0, 598, 2335)	NA Participants B/Florida/04/2006 antigen was not in the influenza vaccine administered to this group.	383 Participants Interval 0.0 to 0.0	1543 Participants Interval 0.0 to 0.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 28 post final vaccination

Population: Seroprotection against influenza vaccine antigens was determined in randomized and vaccinated participants, per-protocol population. Data presented for participants with valid serology results for the particular antigen.

Immunogenicity outcomes were assessed in serum samples by HAI assay. The lower limit of quantitation (LLOQ) was set at the lowest dilution used in the assay, 1/10. Titers below this level were reported as \<10. Seroprotection was defined as a pre-vaccination and post-vaccination titer ≥ 40 (l/dil)

Outcome measures

Outcome measures
Measure	Study Group 1 (Trivalent Influenza Vaccine) n=582 Participants Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Study Group 2 (Investigational Trivalent Influenza Vaccine) n=599 Participants Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Study Group 3 (Investigational Quadrivalent Influenza Vaccine) n=2339 Participants Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants A/H1N1 Pre-vaccination (581, 599, 2333)	291 Participants	305 Participants Interval 0.0 to 0.0	1159 Participants Interval 0.0 to 0.0
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants A/H1N1 Post-vaccination (581, 597, 2337)	573 Participants	585 Participants Interval 0.0 to 0.0	2305 Participants Interval 0.0 to 0.0
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants A/H3N2 Pre-vaccination (579, 596, 2334)	248 Participants	241 Participants Interval 0.0 to 0.0	946 Participants Interval 0.0 to 0.0
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants A/H3N2 Post-vaccination (580, 599, 2334)	575 Participants	593 Participants Interval 0.0 to 0.0	2326 Participants Interval 0.0 to 0.0
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants B/Brisbane Pre-vaccination 582, 599, 2337)	64 Participants	79 Participants Interval 25.0 to 33.7	261 Participants Interval 0.0 to 0.0
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants B/Brisbane Post-vaccination (581, 599, 2338)	418 Participants	202 Participants Interval 0.0 to 0.0	1838 Participants Interval 0.0 to 0.0
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants B/Florida Pre-vaccination (582, 598, 2336)	51 Participants	55 Participants Interval 0.0 to 0.0	199 Participants Interval 0.0 to 0.0
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants B/Florida Post-vaccination (581, 598, 2338)	169 Participants	416 Participants Interval 0.0 to 0.0	1674 Participants Interval 0.0 to 0.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 28 post final vaccination

Population: Seroconversion with respect to vaccine antigens (cross-reactive antibody) were determined in randomized and vaccinated participants, per-protocol population. Data presented for participants with valid serology results for the particular antigen.

Immunogenicity outcomes were assessed in serum samples by HAI assay. The lower limit of quantitation (LLOQ) was set at the lowest dilution used in the assay, 1/10. Titers below this level were reported as \<10. Seroconversion was defined as either a pre vaccination HAI titer \<1:10 and a post vaccination titer ≥1:40 or a pre-vaccination titer ≥1:10 and a four-fold increase in post-vaccination.

Outcome measures

Outcome measures
Measure	Study Group 1 (Trivalent Influenza Vaccine) n=582 Participants Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Study Group 2 (Investigational Trivalent Influenza Vaccine) n=599 Participants Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Study Group 3 (Investigational Quadrivalent Influenza Vaccine) n=2339 Participants Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Seroconversion Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants A/H1N1 (580, 597, 2331)	541 Participants	535 Participants Interval 0.0 to 0.0	2135 Participants Interval 0.0 to 0.0
Seroconversion Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants A/H3N2 (578, 596, 2329)	477 Participants	512 Participants Interval 0.0 to 0.0	2050 Participants Interval 0.0 to 0.0
Seroconversion Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants B/Brisbane (581, 599, 2336)	355 Participants	120 Participants Interval 0.0 to 0.0	1677 Participants Interval 0.0 to 0.0
Seroconversion Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants B/Florida (581, 598, 2335)	104 Participants	383 Participants Interval 0.0 to 0.0	1543 Participants Interval 0.0 to 0.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 28 post final vaccination

Population: Seroconversion with respect to influenza vaccine B antigens (cross-reactive antibody) was determined in randomized and vaccinated participants, per-protocol population. Data presented for participants with valid serology results for the B antigens.

Immunogenicity outcomes were assessed in serum samples by HAI assay. The lower limit of quantitation (LLOQ) was set at the lowest dilution used in the assay, 1/10. Titers below this level were reported as \<10. Seroconversion was defined as either a pre vaccination HAI titer \<1:10 and a post vaccination titer ≥1:40 or a pre-vaccination titer ≥1:10 and a four-fold increase in post-vaccination.

Outcome measures

Outcome measures
Measure	Study Group 1 (Trivalent Influenza Vaccine) n=582 Participants Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Study Group 2 (Investigational Trivalent Influenza Vaccine) n=599 Participants Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Study Group 3 (Investigational Quadrivalent Influenza Vaccine) n=2339 Participants Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Seroconversion Against Influenza B Strains After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines Without Corresponding B Strain in All Participants. B/Brisbane/60/2008 (0, 599, 2336)	NA Participants B/Florida/04/2006 antigen was not in the influenza vaccine administered to this group	120 Participants	1677 Participants
Seroconversion Against Influenza B Strains After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines Without Corresponding B Strain in All Participants. B/Florida/04/2006 (581, 0, 2335)	104 Participants	NA Participants B/Brisbane/60/2008 antigen was not in the influenza vaccine administered to this group	1543 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 28 post final vaccination

Population: Seroprotection against influenza vaccine antigens were determined in randomized and vaccinated participants, per-protocol population. Data presented for participants aged 6 months to less than 36 months with valid serology results for the particular antigen.

Immunogenicity outcomes were assessed in serum samples by HAI assay. The lower limit of quantitation (LLOQ) was set at the lowest dilution used in the assay, 1/10. Titers below this level were reported as \<10. Seroprotection was defined as a pre-vaccination and post-vaccination titer ≥ 40 (l/dil).

Outcome measures

Outcome measures
Measure	Study Group 1 (Trivalent Influenza Vaccine) n=225 Participants Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Study Group 2 (Investigational Trivalent Influenza Vaccine) n=245 Participants Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Study Group 3 (Investigational Quadrivalent Influenza Vaccine) n=949 Participants Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 6 Months to Less Than 36 Months. H1N1 Pre-vaccination (224, 245, 943)	80 Participants	100 Participants	327 Participants
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 6 Months to Less Than 36 Months. H1N1 Post-vaccination (223, 243, 941)	220 Participants	237 Participants	925 Participants
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 6 Months to Less Than 36 Months. H3N2 Pre-vaccination (224, 245, 945)	26 Participants	29 Participants	104 Participants
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 6 Months to Less Than 36 Months. H3N2 Post-vaccination (223, 243, 944)	221 Participants	242 Participants	943 Participants
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 6 Months to Less Than 36 Months. B/Brisbane Pre-vaccination (225, 245, 947)	14 Participants	18 Participants	61 Participants
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 6 Months to Less Than 36 Months. B/Brisbane Post-vaccination (225, 245, 948)	155 Participants	55 Participants	716 Participants
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 6 Months to Less Than 36 Months. B/Florida Pre-vaccination (225, 245, 946)	4 Participants	1 Participants	10 Participants
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 6 Months to Less Than 36 Months. B/Florida Post-vaccination (225, 245, 948)	19 Participants	135 Participants	550 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 28 post-vaccination

Population: Seroprotection against influenza vaccine antigens were determined in randomized and vaccinated participants, per-protocol population. Data presented for participants aged 3 years to less than 9 years with valid serology results for the particular antigen.

Immunogenicity outcomes were assessed in serum samples by HAI assay. The lower limit of quantitation (LLOQ) was set at the lowest dilution used in the assay, 1/10. Titers below this level were reported as \<10. Seroprotection was defined as a pre-vaccination and post-vaccination titer ≥ 40 (l/dil).

Outcome measures

Outcome measures
Measure	Study Group 1 (Trivalent Influenza Vaccine) n=357 Participants Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Study Group 2 (Investigational Trivalent Influenza Vaccine) n=354 Participants Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Study Group 3 (Investigational Quadrivalent Influenza Vaccine) n=1390 Participants Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 3 Years to Less Than 9 Years. H1N1 Pre-vaccination (357, 354, 1390)	211 Participants	205 Participants	832 Participants
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 3 Years to Less Than 9 Years. H1N1 Post-vaccination (357, 354, 1390)	353 Participants	348 Participants	1380 Participants
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 3 Years to Less Than 9 Years. H3N2 Pre-vaccination (355, 353, 1389)	222 Participants	212 Participants	842 Participants
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 3 Years to Less Than 9 Years. H3N2 Post-vaccination (356, 353, 1390)	354 Participants	351 Participants	1383 Participants
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 3 Years to Less Than 9 Years. B/Brisbane Pre-vaccination (357, 354, 1390)	50 Participants	61 Participants	200 Participants
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 3 Years to Less Than 9 Years. B/Brisbane Post-vaccination (356, 354, 1390)	263 Participants	147 Participants	1122 Participants
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 3 Years to Less Than 9 Years. B/Florida Pre-vaccination (357, 353, 1390)	47 Participants	54 Participants	189 Participants
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 3 Years to Less Than 9 Years. B/Florida Post-vaccination (356, 353, 1390)	150 Participants	281 Participants	1124 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 28 post-vaccination

Population: Seroprotection against influenza vaccine antigens were determined in randomized and vaccinated participants, per-protocol population. Data presented for participants with valid serology results for the particular antigen.

Immunogenicity outcomes were assessed in serum samples by HAI assay. The lower limit of quantitation (LLOQ) was set at the lowest dilution used in the assay, 1/10. Titers below this level were reported as \<10. Seroprotection was defined as a pre-vaccination and post-vaccination titer ≥ 40 (l/dil).

Outcome measures

Outcome measures
Measure	Study Group 1 (Trivalent Influenza Vaccine) n=114 Participants Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Study Group 2 (Investigational Trivalent Influenza Vaccine) n=141 Participants Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Study Group 3 (Investigational Quadrivalent Influenza Vaccine) n=510 Participants Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Seroprotection Against Influenza Vaccine Antigens After Vaccination With One Dose of Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants H1N1 Pre-vaccination (114, 141, 510)	62 Participants	89 Participants	289 Participants
Seroprotection Against Influenza Vaccine Antigens After Vaccination With One Dose of Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants H1N1 Post-vaccination (114, 141, 510)	111 Participants	139 Participants	498 Participants
Seroprotection Against Influenza Vaccine Antigens After Vaccination With One Dose of Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants H3N2 Pre-vaccination (112, 141, 510)	64 Participants	75 Participants	259 Participants
Seroprotection Against Influenza Vaccine Antigens After Vaccination With One Dose of Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants H3N2 Post-vaccination (112, 141, 510)	110 Participants	138 Participants	504 Participants
Seroprotection Against Influenza Vaccine Antigens After Vaccination With One Dose of Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants B/Brisbane Pre-vaccination (114, 141, 510)	15 Participants	25 Participants	66 Participants
Seroprotection Against Influenza Vaccine Antigens After Vaccination With One Dose of Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants B/Brisbane Post-vaccination (113, 141, 510)	72 Participants	55 Participants	341 Participants
Seroprotection Against Influenza Vaccine Antigens After Vaccination With One Dose of Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants B/Florida Pre-vaccination (114, 141, 510)	18 Participants	20 Participants	58 Participants
Seroprotection Against Influenza Vaccine Antigens After Vaccination With One Dose of Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants B/Florida Post-vaccination (113, 141, 510)	46 Participants	98 Participants	350 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 28 post final vaccination

Population: Seroprotection against influenza vaccine antigens were determined in randomized and vaccinated participants, per-protocol population. Data presented for participants with valid serology results for the particular antigen.

Immunogenicity outcomes were assessed in serum samples by HAI assay. The lower limit of quantitation (LLOQ) was set at the lowest dilution used in the assay, 1/10. Titers below this level were reported as \<10. Seroprotection was defined as a pre-vaccination and post-vaccination titer ≥ 40 (l/dil).

Outcome measures

Outcome measures
Measure	Study Group 1 (Trivalent Influenza Vaccine) n=468 Participants Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Study Group 2 (Investigational Trivalent Influenza Vaccine) n=458 Participants Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Study Group 3 (Investigational Quadrivalent Influenza Vaccine) n=1829 Participants Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Two Doses of Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants H1N1 Pre-vaccination (467, 458, 1823)	229 Participants	216 Participants	870 Participants
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Two Doses of Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants H1N1 Post-vaccination (467, 456, 1827)	462 Participants	446 Participants	1807 Participants
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Two Doses of Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants H3N2 Pre-vaccination (467, 457, 1824)	184 Participants	166 Participants	687 Participants
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Two Doses of Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants H3N2 Post-vaccination (467, 455, 1824)	465 Participants	455 Participants	1822 Participants
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Two Doses of Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants B/Brisbane Pre-vaccination (468, 458, 1827)	49 Participants	54 Participants	195 Participants
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Two Doses of Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants B/Brisbane Post-vaccination (468, 458, 1828)	346 Participants	147 Participants	1497 Participants
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Two Doses of Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants B/Florida Pre-vaccination (468, 457, 1826)	33 Participants	35 Participants	141 Participants
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Two Doses of Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants B/Florida Post-vaccination (468, 457, 1828)	123 Participants	318 Participants	1324 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 0 up to Day 7 post-vaccination

Population: Safety profile were assessed in all randomized and vaccinated participants, safety population. Values presented for participants aged 6 months to \<36 months with available data for the relevant endpoint.

Solicited injection site reactions (Age 6-23 Months): Tenderness, Erythema and Swelling. Solicited systemic reactions: Fever (Temperature), Vomiting, Abnormal crying, Drowsiness, Loss of appetite, and Irritability. Grade 3: Tenderness: cries when injected limb is moved; Erythema and Swelling ≥ 50 mm; Fever: \>103.1°F; Vomiting: ≥6 episodes/24 hours; Abnormal crying: \>3 hours; Drowsiness: Sleeping most of the time; Loss of appetite: refuses ≥3 feeds/meals or most feeds/meals; Irritability: inconsolable. Solicited Injection site reactions (Age 24 Months to \< 36 months): Pain, Erythema, and Swelling. Systemic reactions: Fever (Temperature), Headache, Malaise, and Myalgia. Grade 3: Pain: Incapacitating, unable to perform usual activities; Redness and Swelling: ≥ 50 mm; Fever: ≥102.1°F; Headache, Malaise and Myalgia: Significant, prevents daily activity.

Outcome measures

Outcome measures
Measure	Study Group 1 (Trivalent Influenza Vaccine) n=310 Participants Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Study Group 2 (Investigational Trivalent Influenza Vaccine) n=308 Participants Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Study Group 3 (Investigational Quadrivalent Influenza Vaccine) n=1223 Participants Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Number of Participants Aged 6 Months to <36 Months Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines. Injection site Pain (130, 149, 521)	68 Participants	75 Participants Interval 0.0 to 0.0	297 Participants Interval 0.0 to 0.0
Number of Participants Aged 6 Months to <36 Months Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines. Grade 3 Injection site Pain (130, 149, 521)	1 Participants	4 Participants Interval 0.0 to 0.0	5 Participants Interval 0.0 to 0.0
Number of Participants Aged 6 Months to <36 Months Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines. Injection site Tenderness (159, 145, 628)	77 Participants	72 Participants	340 Participants
Number of Participants Aged 6 Months to <36 Months Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines. Grade 3 Injection site Tenderness (159, 145, 628)	3 Participants	0 Participants	12 Participants
Number of Participants Aged 6 Months to <36 Months Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines. Injection site Erythema (289, 294, 1150)	95 Participants	98 Participants Interval 0.0 to 0.0	429 Participants Interval 0.0 to 0.0
Number of Participants Aged 6 Months to <36 Months Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines. Grade 3 Injection site Erythema (289, 294, 1150)	0 Participants	0 Participants Interval 0.0 to 0.0	2 Participants Interval 0.0 to 0.0
Number of Participants Aged 6 Months to <36 Months Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines. Injection site Swelling (289, 294, 1150)	57 Participants	51 Participants Interval 0.0 to 0.0	248 Participants Interval 0.0 to 0.0
Number of Participants Aged 6 Months to <36 Months Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines. Grade 3 Injection site Swelling (289, 294, 1150)	0 Participants	0 Participants Interval 0.0 to 0.0	2 Participants Interval 0.0 to 0.0
Number of Participants Aged 6 Months to <36 Months Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines. Fever (288, 293, 1148)	46 Participants	38 Participants Interval 0.0 to 0.0	164 Participants Interval 0.0 to 0.0
Number of Participants Aged 6 Months to <36 Months Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines. Grade 3 Fever (288, 293, 1148)	5 Participants	6 Participants Interval 0.0 to 0.0	24 Participants Interval 0.0 to 0.0
Number of Participants Aged 6 Months to <36 Months Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines. Vomiting (159, 144, 628)	18 Participants	20 Participants	93 Participants
Number of Participants Aged 6 Months to <36 Months Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines. Grade 3 Vomiting (159, 144, 628)	1 Participants	0 Participants	6 Participants
Number of Participants Aged 6 Months to <36 Months Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines. Crying abnormal (159, 144, 628)	58 Participants	43 Participants	259 Participants
Number of Participants Aged 6 Months to <36 Months Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines. Grade 3 Crying abnormal (159, 144, 628)	3 Participants	3 Participants	21 Participants
Number of Participants Aged 6 Months to <36 Months Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines. Drowsiness (159, 144, 628)	51 Participants	46 Participants	237 Participants
Number of Participants Aged 6 Months to <36 Months Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines. Grade 3 Drowsiness (159, 144, 628)	1 Participants	1 Participants	8 Participants
Number of Participants Aged 6 Months to <36 Months Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines. Headache (128, 148, 517)	12 Participants	18 Participants Interval 0.0 to 0.0	46 Participants Interval 0.0 to 0.0
Number of Participants Aged 6 Months to <36 Months Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines. Grade 3 Headache (128, 148, 517)	0 Participants	0 Participants Interval 0.0 to 0.0	3 Participants Interval 0.0 to 0.0
Number of Participants Aged 6 Months to <36 Months Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines. Appetite lost (159, 144, 628)	53 Participants	36 Participants	203 Participants
Number of Participants Aged 6 Months to <36 Months Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines. Grade 3 Appetite lost (159, 144, 628)	3 Participants	1 Participants	11 Participants
Number of Participants Aged 6 Months to <36 Months Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines. Malaise (128, 148, 517)	45 Participants	48 Participants Interval 0.0 to 0.0	197 Participants Interval 0.0 to 0.0
Number of Participants Aged 6 Months to <36 Months Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines. Grade Malaise (128, 148, 517)	6 Participants	10 Participants Interval 0.0 to 0.0	24 Participants Interval 0.0 to 0.0
Number of Participants Aged 6 Months to <36 Months Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines. Myalgia (128, 148, 517)	34 Participants	37 Participants Interval 0.0 to 0.0	138 Participants Interval 0.0 to 0.0
Number of Participants Aged 6 Months to <36 Months Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines. Grade 3 Myalgia (128, 148, 517)	2 Participants	4 Participants Interval 0.0 to 0.0	10 Participants Interval 0.0 to 0.0
Number of Participants Aged 6 Months to <36 Months Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines. Irritability (159, 144, 628)	84 Participants	77 Participants	339 Participants
Number of Participants Aged 6 Months to <36 Months Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines. Grade 3 Irritability (159, 144, 628)	5 Participants	4 Participants	20 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 0 up to Day 7 post-vaccination

Population: Safety profile were assessed in all randomized and vaccinated participants, safety population. Values presented for participants aged 3 years to \<9 years with available data for the relevant endpoint.

Solicited injection site reactions: Pain, Redness, and Swelling. Solicited systemic reactions: Fever (Temperature); Headache, Malaise and Myalgia Grade 3 Pain: incapacitating, unable to perform usual activities; Redness and Swelling: ≥ 50 mm; Fever: ≥ 102.1°F; Headache, Malaise and Myalgia: Significant, prevents daily activity, respectively.

Outcome measures

Outcome measures
Measure	Study Group 1 (Trivalent Influenza Vaccine) n=424 Participants Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Study Group 2 (Investigational Trivalent Influenza Vaccine) n=413 Participants Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Study Group 3 (Investigational Quadrivalent Influenza Vaccine) n=1669 Participants Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Number of Participants Aged 3 Years to <9 Years Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines Injection site Pain (410, 398, 1592)	265 Participants	254 Participants	1061 Participants
Number of Participants Aged 3 Years to <9 Years Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines Grade 3 Injection site Pain (410, 398, 1592)	8 Participants	11 Participants	33 Participants
Number of Participants Aged 3 Years to <9 Years Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines Injection site Erythema (410, 398, 1592)	151 Participants	140 Participants	543 Participants
Number of Participants Aged 3 Years to <9 Years Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines Grade 3 Injection site Erythema (410, 398, 1592)	5 Participants	7 Participants	29 Participants
Number of Participants Aged 3 Years to <9 Years Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines Injection site Swelling (410, 398, 1592)	104 Participants	103 Participants	395 Participants
Number of Participants Aged 3 Years to <9 Years Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines Grade 3 Injection site Swelling (410, 398, 1592)	5 Participants	7 Participants	22 Participants
Number of Participants Aged 3 Years to <9 Years Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines Fever (409, 396, 1591)	29 Participants	30 Participants	112 Participants
Number of Participants Aged 3 Years to <9 Years Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines Grade 3 Fever (409, 396, 1591)	5 Participants	3 Participants	34 Participants
Number of Participants Aged 3 Years to <9 Years Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines Headache (411, 398, 1593)	87 Participants	97 Participants	368 Participants
Number of Participants Aged 3 Years to <9 Years Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines Grade 3 Headache (411, 398, 1593)	11 Participants	8 Participants	35 Participants
Number of Participants Aged 3 Years to <9 Years Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines Malaise (411, 398, 1593)	135 Participants	133 Participants	508 Participants
Number of Participants Aged 3 Years to <9 Years Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines Grade 3 Malaise (411, 398, 1593)	23 Participants	20 Participants	87 Participants
Number of Participants Aged 3 Years to <9 Years Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines Myalgia (411, 398, 1593)	140 Participants	153 Participants	615 Participants
Number of Participants Aged 3 Years to <9 Years Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines Grade 3 Myalgia (411, 398, 1593)	11 Participants	11 Participants	52 Participants

Adverse Events

Study Group 1 (Trivalent Influenza Vaccine)

Serious events: 7 serious events

Other events: 333 other events

Deaths: 0 deaths

Study Group 2 (Investigational Trivalent Influenza Vaccine)

Serious events: 14 serious events

Other events: 329 other events

Deaths: 0 deaths

Study Group 3 (Investigational Quadrivalent Influenza Vaccine)

Serious events: 41 serious events

Other events: 1358 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Director

Sanofi Pasteur Inc.

Email: [email protected]

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

Measure	Study Group 1 (Trivalent Influenza Vaccine) n=734 participants at risk Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Study Group 2 (Investigational Trivalent Influenza Vaccine) n=721 participants at risk Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Study Group 3 (Investigational Quadrivalent Influenza Vaccine) n=2892 participants at risk Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
General disorders Injection site pain	61.7% 333/540 • Number of events 333 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	60.1% 329/547 • Number of events 329 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	64.3% 1358/2113 • Number of events 1358 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.
General disorders Injection site Swelling	21.9% 161/734 • Number of events 162 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	22.3% 154/692 • Number of events 154 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	23.5% 643/2742 • Number of events 643 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.
Nervous system disorders Headache	18.4% 99/539 • Number of events 99 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	21.1% 115/546 • Number of events 115 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	19.6% 414/2110 • Number of events 414 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.
General disorders Malaise	33.4% 180/539 • Number of events 180 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	33.2% 181/546 • Number of events 181 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	33.4% 705/2110 • Number of events 705 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.
Musculoskeletal and connective tissue disorders Myalgia	32.3% 174/539 • Number of events 174 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	34.8% 190/546 • Number of events 190 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	35.7% 753/2110 • Number of events 753 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.
General disorders Injection site tenderness	48.4% 77/159 • Number of events 77 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	49.7% 72/145 • Number of events 72 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	54.1% 340/628 • Number of events 340 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.
General disorders Injection site erythema	35.2% 246/699 • Number of events 246 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	34.4% 238/692 • Number of events 238 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	35.4% 972/2742 • Number of events 972 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.
General disorders Fever	10.8% 75/695 • Number of events 75 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	9.9% 68/689 • Number of events 68 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	10.1% 276/2739 • Number of events 276 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.
Gastrointestinal disorders Vomiting	6.3% 46/734 • Number of events 52 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	7.6% 55/721 • Number of events 61 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	6.7% 193/2892 • Number of events 209 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.
Metabolism and nutrition disorders Appetite lost	33.3% 53/159 • Number of events 53 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	25.0% 36/144 • Number of events 36 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	32.3% 203/628 • Number of events 203 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.
Nervous system disorders Drowsiness	32.1% 51/159 • Number of events 51 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	31.9% 46/144 • Number of events 46 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	37.7% 237/628 • Number of events 237 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.
Psychiatric disorders Crying abnormal	36.5% 58/159 • Number of events 58 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	29.9% 43/144 • Number of events 43 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	41.2% 259/628 • Number of events 259 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.
Psychiatric disorders Irritability	52.8% 84/159 • Number of events 84 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	53.5% 77/144 • Number of events 77 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	54.0% 339/628 • Number of events 339 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.
Gastrointestinal disorders Diarrhoea	5.7% 42/734 • Number of events 51 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	5.3% 38/721 • Number of events 48 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	4.7% 135/2892 • Number of events 150 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.
General disorders Pyrexia	6.0% 44/734 • Number of events 49 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	9.0% 65/721 • Number of events 75 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	6.5% 188/2892 • Number of events 213 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.
Infections and infestations Upper respiratory tract infection	5.9% 43/734 • Number of events 51 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	6.5% 47/721 • Number of events 50 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	6.4% 184/2892 • Number of events 203 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.
Respiratory, thoracic and mediastinal disorders Cough	12.9% 95/734 • Number of events 107 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	12.3% 89/721 • Number of events 100 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	11.8% 341/2892 • Number of events 381 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	5.0% 37/734 • Number of events 38 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	4.7% 34/721 • Number of events 39 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.	5.8% 167/2892 • Number of events 189 • Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination. Data are presented for participants with available safety data for the relevant endpoints.