Study of Quadrivalent Influenza Vaccine Among Children

• ClinicalTrials.gov Identifier: NCT01240746
• Recruitment Status: Completed
• First Posted: November 15, 2010
• Results First Posted: January 14, 2014
• Last Update Posted: July 14, 2015
• Sponsor: Sanofi Pasteur, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Influenza
• Interventions: Biological: Licensed 2010-2011 Trivalent Influenza Vaccine, No Preservative; Biological: Investigational Trivalent Influenza Vaccine with alternate B strain, No Preservative; Biological: Quadrivalent Influenza Vaccine, No Preservative
• Enrollment: 4363

Participant Flow

Recruitment Details	The study participants were enrolled from 11 November 2010 to 20 June 2011 in 69 clinical centers in the US
Pre-assignment Details	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.

Arm/Group Title	Study Group 1 (2010-2011 Trivalent Influenza Vaccine)	Study Group 2 (Investigational Trivalent Influenza Vaccine)	Study Group 3 (Investigational Quadrivalent Influenza Vaccine)
Arm/Group Description	Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen.	Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Period Title: Overall Study
Started	736	725	2902
Completed	677	677	2659
Not Completed	59	48	243
Reason Not Completed
Adverse Event	2	0	10
Lost to Follow-up	23	20	102
Protocol Violation	24	15	72
Withdrawal by Subject	10	13	59

Baseline Characteristics

Arm/Group Title		Study Group 1 (Trivalent Influenza Vaccine)	Study Group 2 (Investigational Trivalent Influenza Vaccine)	Study Group 3 (Investigational Quadrivalent Influenza Vaccine)	Total
Arm/Group Description		Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)	Total of all reporting groups
Overall Number of Baseline Participants		736	725	2902	4363
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	736 participants	725 participants	2902 participants	4363 participants
	<=18 years	736 100.0%	725 100.0%	2902 100.0%	4363 100.0%
	Between 18 and 65 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Months
	Number Analyzed	736 participants	725 participants	2902 participants	4363 participants
		49.6 (29.0)	49.6 (28.7)	49.8 (29.7)	49.8 (29.4)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	736 participants	725 participants	2902 participants	4363 participants
	Female	367 49.9%	359 49.5%	1427 49.2%	2153 49.3%
	Male	369 50.1%	366 50.5%	1475 50.8%	2210 50.7%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	736 participants	725 participants	2902 participants	4363 participants
		736	725	2902	4363

Outcome Measures

1. Primary Outcome

Title	Geometric Mean Titers Against Influenza A Strains After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants
Description	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.
Time Frame	Day 28 post final vaccination

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Study Group 1 (Trivalent Influenza Vaccine)	Study Group 2 (Investigational Trivalent Influenza Vaccine)	Study Group 3 (Investigational Quadrivalent Influenza Vaccine)
Arm/Group Description:	Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Overall Number of Participants Analyzed	1461	0	2339
Geometric Mean (95% Confidence Interval); Unit of Measure: Titers
A/California/07/2009 (A/H1N1) [N = 1461, 0, 2339]	1096; (1008 to 1192)		1124; (1060 to 1192)
A/Victoria/210/2009 (A/H3N2) [N = 1461, 0, 2339	828; (774 to 887)		822; (783 to 862)

2. Primary Outcome

Title	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
Description	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.
Time Frame	Day 28 post final vaccination

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Study Group 1 (Trivalent Influenza Vaccine)	Study Group 2 (Investigational Trivalent Influenza Vaccine)	Study Group 3 (Investigational Quadrivalent Influenza Vaccine)
Arm/Group Description:	Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Overall Number of Participants Analyzed	582	599	2339
Geometric Mean (95% Confidence Interval); Unit of Measure: Titers
B/Brisbane/60/2008 (581, 0, 2238)	64.3; (58.3 to 70.9)	NA [1]; (NA to NA)	86.1; (81.8 to 90.6)
B/Florida/04/2006 (0, 598, 2338)	NA [2]; (NA to NA)	58.3; (52.6 to 64.7)	61.5; (58.6 to 64.7)

[1]

B/Brisbane/60/2008 antigen was not in the influenza vaccine administered to this group.

[2]

B/Florida/04/2006 antigen was not in the influenza vaccine administered to this group.

3. Primary Outcome

Title	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
Description	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.
Time Frame	Day 28 post final vaccination

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Study Group 1 (Trivalent Influenza Vaccine)	Study Group 2 (Investigational Trivalent Influenza Vaccine)	Study Group 3 (Investigational Quadrivalent Influenza Vaccine)
Arm/Group Description:	Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Overall Number of Participants Analyzed	582	599	2339
Geometric Mean (95% Confidence Interval); Unit of Measure: Titers
B/Brisbane/60/2008 (0, 599, 2338)	NA [1]; (NA to NA)	19.5; (17.4 to 21.8)	86.1; (81.8 to 90.6)
B/Florida/04/2006 (581, 0, 2338)	16.3; (14.8 to 17.9)	NA [2]; (NA to NA)	61.5; (58.6 to 64.7)

[1]

B/Florida/04/2006 antigen was not in the influenza vaccine administered to this group.

[2]

B/Brisbane/60/2008 antigen was not in the influenza vaccine administered to this group.

4. Primary Outcome

Title	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.
Description	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.
Time Frame	Day 28 post final vaccination

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Study Group 1 (Trivalent Influenza Vaccine)	Study Group 2 (Investigational Trivalent Influenza Vaccine)	Study Group 3 (Investigational Quadrivalent Influenza Vaccine)
Arm/Group Description:	Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Overall Number of Participants Analyzed	225	245	949
Geometric Mean (95% Confidence Interval); Unit of Measure: Titers
A/H1N1, Pre-vaccination (224, 245, 943)	25.6; (19.4 to 33.7)	31.3; (23.8 to 41.1)	25.7; (22.4 to 29.5)
A/H1N1, Post-vaccination (224, 243, 947)	797; (664 to 957)	645; (530 to 784)	747; (680 to 821)
A/H3N2, Pre-vaccination (224, 245, 945)	9.52; (7.90 to 11.5)	10.1; (8.26 to 12.3)	9.19; (8.42 to 10.0)
A/H3N2, Post-vaccination (224, 243, 944)	558; (483 to 646)	583; (507 to 671)	526; (492 to 562)
B/Brisbane, Pre-vaccination (225, 245, 947)	6.56; (5.92 to 7.27)	6.62; (6.00 to 7.30)	6.41; (6.10 to 6.73)
B/Brisbane, Post-vaccination (225, 245, 948)	54.7; (47.2 to 63.4)	12.0; (10.3 to 13.9)	72.8; (67.3 to 78.7)
B/Florida, Pre-vaccination (225, 245, 946)	5.33; (5.10 to 5.56)	5.26; (5.09 to 5.44)	5.34; (5.23 to 5.46)
B/Florida, Post-vaccination (225, 245, 948)	8.56; (7.68 to 9.54)	32.9; (28.7 to 37.6)	36.2; (33.7 to 38.8)

5. Primary Outcome

Title	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.
Description	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.
Time Frame	Day 28 post-vaccination

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Study Group 1 (Trivalent Influenza Vaccine)	Study Group 2 (Investigational Trivalent Influenza Vaccine)	Study Group 3 (Investigational Quadrivalent Influenza Vaccine)
Arm/Group Description:	Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Overall Number of Participants Analyzed	357	354	1390
Geometric Mean (95% Confidence Interval); Unit of Measure: Titers
A/H1N1, Pre-vaccination (357, 354, 1390)	53.5; (43.9 to 65.2)	54.4; (44.4 to 66.8)	54.9; (49.6 to 60.7)
A/H1N1, Post-vaccination (357, 354, 1390)	1565; (1355 to 1807)	1348; (1166 to 1559)	1484; (1380 to 1595)
A/H3N2, Pre-vaccination (355, 353, 1389)	70.6; (57.3 to 87.0)	64.1; (51.9 to 79.2)	63.9; (57.6 to 70.8)
A/H3N2, Post-vaccination (356, 353, 1390)	924; (816 to 1046)	1214; (1078 to 1367)	1112; (1046 to 1183)
B/Brisbane, Pre-vaccination (357, 354, 1390)	10.1; (9.05 to 11.2)	10.6; (9.52 to 11.9)	9.73; (9.23 to 10.3)
B/Brisbane, Post-vaccination (356, 354, 1390)	71.2; (62.6 to 81.1)	27.3; (23.4 to 31.8)	96.6; (90.3 to 103)
B/Florida, Pre-vaccination (357, 353, 1390)	9.09; (8.26 to 10.0)	9.84; (8.91 to 10.9)	9.34; (8.89 to 9.82)
B/Florida, Post-vaccination (356, 353, 1390)	24.4; (21.6 to 27.5)	86.9; (76.1 to 99.2)	88.5; (83.1 to 94.1)

6. Other Pre-specified Outcome

Title	Seroconversion Against Influenza B Strains After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines With Corresponding B Strain in All Participants
Description	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
Time Frame	Day 28 post final vaccination

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Study Group 1 (Trivalent Influenza Vaccine)	Study Group 2 (Investigational Trivalent Influenza Vaccine)	Study Group 3 (Investigational Quadrivalent Influenza Vaccine)
Arm/Group Description:	Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Overall Number of Participants Analyzed	582	599	2339
Measure Type: Number; Unit of Measure: Participants
B/Brisbane/60/2008 (581, 0, 2336)	355	NA [1]	1677
B/Florida/04/2006 (0, 598, 2335)	NA [2]	383	1543

[1]

B/Brisbane/60/2008 antigen was not in the influenza vaccine administered to this group.

[2]

B/Florida/04/2006 antigen was not in the influenza vaccine administered to this group.

7. Other Pre-specified Outcome

Title	Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants
Description	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)
Time Frame	Day 28 post final vaccination

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Study Group 1 (Trivalent Influenza Vaccine)	Study Group 2 (Investigational Trivalent Influenza Vaccine)	Study Group 3 (Investigational Quadrivalent Influenza Vaccine)
Arm/Group Description:	Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Overall Number of Participants Analyzed	582	599	2339
Measure Type: Number; Unit of Measure: Participants
A/H1N1 Pre-vaccination (581, 599, 2333)	291	305	1159
A/H1N1 Post-vaccination (581, 597, 2337)	573	585	2305
A/H3N2 Pre-vaccination (579, 596, 2334)	248	241	946
A/H3N2 Post-vaccination (580, 599, 2334)	575	593	2326
B/Brisbane Pre-vaccination 582, 599, 2337)	64	79	261
B/Brisbane Post-vaccination (581, 599, 2338)	418	202	1838
B/Florida Pre-vaccination (582, 598, 2336)	51	55	199
B/Florida Post-vaccination (581, 598, 2338)	169	416	1674

8. Other Pre-specified Outcome

Title	Seroconversion Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants
Description	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.
Time Frame	Day 28 post final vaccination

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Study Group 1 (Trivalent Influenza Vaccine)	Study Group 2 (Investigational Trivalent Influenza Vaccine)	Study Group 3 (Investigational Quadrivalent Influenza Vaccine)
Arm/Group Description:	Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Overall Number of Participants Analyzed	582	599	2339
Measure Type: Number; Unit of Measure: Participants
A/H1N1 (580, 597, 2331)	541	535	2135
A/H3N2 (578, 596, 2329)	477	512	2050
B/Brisbane (581, 599, 2336)	355	120	1677
B/Florida (581, 598, 2335)	104	383	1543

9. Other Pre-specified Outcome

Title	Seroconversion Against Influenza B Strains After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines Without Corresponding B Strain in All Participants.
Description	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.
Time Frame	Day 28 post final vaccination

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Study Group 1 (Trivalent Influenza Vaccine)	Study Group 2 (Investigational Trivalent Influenza Vaccine)	Study Group 3 (Investigational Quadrivalent Influenza Vaccine)
Arm/Group Description:	Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Overall Number of Participants Analyzed	582	599	2339
Measure Type: Number; Unit of Measure: Participants
B/Brisbane/60/2008 (0, 599, 2336)	NA [1]	120	1677
B/Florida/04/2006 (581, 0, 2335)	104	NA [2]	1543

[1]

B/Florida/04/2006 antigen was not in the influenza vaccine administered to this group

[2]

B/Brisbane/60/2008 antigen was not in the influenza vaccine administered to this group

10. Other Pre-specified Outcome

Title	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.
Description	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).
Time Frame	Day 28 post final vaccination

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Study Group 1 (Trivalent Influenza Vaccine)	Study Group 2 (Investigational Trivalent Influenza Vaccine)	Study Group 3 (Investigational Quadrivalent Influenza Vaccine)
Arm/Group Description:	Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Overall Number of Participants Analyzed	225	245	949
Measure Type: Number; Unit of Measure: Participants
H1N1 Pre-vaccination (224, 245, 943)	80	100	327
H1N1 Post-vaccination (223, 243, 941)	220	237	925
H3N2 Pre-vaccination (224, 245, 945)	26	29	104
H3N2 Post-vaccination (223, 243, 944)	221	242	943
B/Brisbane Pre-vaccination (225, 245, 947)	14	18	61
B/Brisbane Post-vaccination (225, 245, 948)	155	55	716
B/Florida Pre-vaccination (225, 245, 946)	4	1	10
B/Florida Post-vaccination (225, 245, 948)	19	135	550

11. Other Pre-specified Outcome

Title	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.
Description	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).
Time Frame	Day 28 post-vaccination

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Study Group 1 (Trivalent Influenza Vaccine)	Study Group 2 (Investigational Trivalent Influenza Vaccine)	Study Group 3 (Investigational Quadrivalent Influenza Vaccine)
Arm/Group Description:	Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Overall Number of Participants Analyzed	357	354	1390
Measure Type: Number; Unit of Measure: Participants
H1N1 Pre-vaccination (357, 354, 1390)	211	205	832
H1N1 Post-vaccination (357, 354, 1390)	353	348	1380
H3N2 Pre-vaccination (355, 353, 1389)	222	212	842
H3N2 Post-vaccination (356, 353, 1390)	354	351	1383
B/Brisbane Pre-vaccination (357, 354, 1390)	50	61	200
B/Brisbane Post-vaccination (356, 354, 1390)	263	147	1122
B/Florida Pre-vaccination (357, 353, 1390)	47	54	189
B/Florida Post-vaccination (356, 353, 1390)	150	281	1124

12. Other Pre-specified Outcome

Title	Seroprotection Against Influenza Vaccine Antigens After Vaccination With One Dose of Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants
Description	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).
Time Frame	Day 28 post-vaccination

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Study Group 1 (Trivalent Influenza Vaccine)	Study Group 2 (Investigational Trivalent Influenza Vaccine)	Study Group 3 (Investigational Quadrivalent Influenza Vaccine)
Arm/Group Description:	Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Overall Number of Participants Analyzed	114	141	510
Measure Type: Number; Unit of Measure: Participants
H1N1 Pre-vaccination (114, 141, 510)	62	89	289
H1N1 Post-vaccination (114, 141, 510)	111	139	498
H3N2 Pre-vaccination (112, 141, 510)	64	75	259
H3N2 Post-vaccination (112, 141, 510)	110	138	504
B/Brisbane Pre-vaccination (114, 141, 510)	15	25	66
B/Brisbane Post-vaccination (113, 141, 510)	72	55	341
B/Florida Pre-vaccination (114, 141, 510)	18	20	58
B/Florida Post-vaccination (113, 141, 510)	46	98	350

13. Other Pre-specified Outcome

Title	Seroprotection Against Influenza Vaccine Antigens After Vaccination With Two Doses of Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants
Description	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).
Time Frame	Day 28 post final vaccination

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Study Group 1 (Trivalent Influenza Vaccine)	Study Group 2 (Investigational Trivalent Influenza Vaccine)	Study Group 3 (Investigational Quadrivalent Influenza Vaccine)
Arm/Group Description:	Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Overall Number of Participants Analyzed	468	458	1829
Measure Type: Number; Unit of Measure: Participants
H1N1 Pre-vaccination (467, 458, 1823)	229	216	870
H1N1 Post-vaccination (467, 456, 1827)	462	446	1807
H3N2 Pre-vaccination (467, 457, 1824)	184	166	687
H3N2 Post-vaccination (467, 455, 1824)	465	455	1822
B/Brisbane Pre-vaccination (468, 458, 1827)	49	54	195
B/Brisbane Post-vaccination (468, 458, 1828)	346	147	1497
B/Florida Pre-vaccination (468, 457, 1826)	33	35	141
B/Florida Post-vaccination (468, 457, 1828)	123	318	1324

14. Other Pre-specified Outcome

Title	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.
Description	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.
Time Frame	Day 0 up to Day 7 post-vaccination

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Study Group 1 (Trivalent Influenza Vaccine)	Study Group 2 (Investigational Trivalent Influenza Vaccine)	Study Group 3 (Investigational Quadrivalent Influenza Vaccine)
Arm/Group Description:	Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Overall Number of Participants Analyzed	310	308	1223
Measure Type: Number; Unit of Measure: Participants
Injection site Pain (130, 149, 521)	68	75	297
Grade 3 Injection site Pain (130, 149, 521)	1	4	5
Injection site Tenderness (159, 145, 628)	77	72	340
Grade 3 Injection site Tenderness (159, 145, 628)	3	0	12
Injection site Erythema (289, 294, 1150)	95	98	429
Grade 3 Injection site Erythema (289, 294, 1150)	0	0	2
Injection site Swelling (289, 294, 1150)	57	51	248
Grade 3 Injection site Swelling (289, 294, 1150)	0	0	2
Fever (288, 293, 1148)	46	38	164
Grade 3 Fever (288, 293, 1148)	5	6	24
Vomiting (159, 144, 628)	18	20	93
Grade 3 Vomiting (159, 144, 628)	1	0	6
Crying abnormal (159, 144, 628)	58	43	259
Grade 3 Crying abnormal (159, 144, 628)	3	3	21
Drowsiness (159, 144, 628)	51	46	237
Grade 3 Drowsiness (159, 144, 628)	1	1	8
Headache (128, 148, 517)	12	18	46
Grade 3 Headache (128, 148, 517)	0	0	3
Appetite lost (159, 144, 628)	53	36	203
Grade 3 Appetite lost (159, 144, 628)	3	1	11
Malaise (128, 148, 517)	45	48	197
Grade Malaise (128, 148, 517)	6	10	24
Myalgia (128, 148, 517)	34	37	138
Grade 3 Myalgia (128, 148, 517)	2	4	10
Irritability (159, 144, 628)	84	77	339
Grade 3 Irritability (159, 144, 628)	5	4	20

15. Other Pre-specified Outcome

Title	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
Description	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.
Time Frame	Day 0 up to Day 7 post-vaccination

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Study Group 1 (Trivalent Influenza Vaccine)	Study Group 2 (Investigational Trivalent Influenza Vaccine)	Study Group 3 (Investigational Quadrivalent Influenza Vaccine)
Arm/Group Description:	Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen	Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen	Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
Overall Number of Participants Analyzed	424	413	1669
Measure Type: Number; Unit of Measure: Participants
Injection site Pain (410, 398, 1592)	265	254	1061
Grade 3 Injection site Pain (410, 398, 1592)	8	11	33
Injection site Erythema (410, 398, 1592)	151	140	543
Grade 3 Injection site Erythema (410, 398, 1592)	5	7	29
Injection site Swelling (410, 398, 1592)	104	103	395
Grade 3 Injection site Swelling (410, 398, 1592)	5	7	22
Fever (409, 396, 1591)	29	30	112
Grade 3 Fever (409, 396, 1591)	5	3	34
Headache (411, 398, 1593)	87	97	368
Grade 3 Headache (411, 398, 1593)	11	8	35
Malaise (411, 398, 1593)	135	133	508
Grade 3 Malaise (411, 398, 1593)	23	20	87
Myalgia (411, 398, 1593)	140	153	615
Grade 3 Myalgia (411, 398, 1593)	11	11	52

Adverse Events

Time Frame	Adverse events data were collected from Day 0 (post-vaccination) up to 6 months post-vaccination.
Adverse Event Reporting Description	Data are presented for participants with available safety data for the relevant endpoints.
Arm/Group Title	Study Group 1 (Trivalent Influenza Vaccine)		Study Group 2 (Investigational Trivalent Influenza Vaccine)		Study Group 3 (Investigational Quadrivalent Influenza Vaccine)
Arm/Group Description	Participants received the Licensed 2010-2011 Trivalent Influenza Vaccine (TIV) containing the primary B strain influenza antigen		Participants received the Investigational Trivalent Influenza Vaccine (TIV) containing the alternate B strain influenza antigen		Participants received the Investigational Quadrivalent Influenza Vaccine (QIV)
All-Cause Mortality
	Study Group 1 (Trivalent Influenza Vaccine)		Study Group 2 (Investigational Trivalent Influenza Vaccine)		Study Group 3 (Investigational Quadrivalent Influenza Vaccine)
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--
Serious Adverse Events
	Study Group 1 (Trivalent Influenza Vaccine)		Study Group 2 (Investigational Trivalent Influenza Vaccine)		Study Group 3 (Investigational Quadrivalent Influenza Vaccine)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/734 (0.95%)		14/721 (1.94%)		41/2892 (1.42%)
Cardiac disorders
Bradycardia * 1	0/734 (0.00%)	0	0/721 (0.00%)	0	1/2892 (0.03%)	1
General disorders
Drowning * 1	1/225 (0.44%)	1	0/721 (0.00%)	0	0/2892 (0.00%)	0
Pyrexia * 1	0/734 (0.00%)	0	0/721 (0.00%)	0	1/2892 (0.03%)	1
Infections and infestations
Appendicitis * 1	0/734 (0.00%)	0	1/721 (0.14%)	1	0/2892 (0.00%)	0
Croup infectious * 1	0/734 (0.00%)	0	0/721 (0.00%)	0	1/2892 (0.03%)	1
Gastroenteritis * 1	0/734 (0.00%)	0	2/721 (0.28%)	2	2/2892 (0.07%)	2
Gastroenteritis viral * 1	0/734 (0.00%)	0	0/721 (0.00%)	0	1/2892 (0.03%)	1
Mycoplasma infection * 1	0/734 (0.00%)	0	1/721 (0.14%)	1	0/2892 (0.00%)	0
Otitis media * 1	0/734 (0.00%)	0	1/721 (0.14%)	1	0/2892 (0.00%)	0
Periorbital cellulitis * 1	0/734 (0.00%)	0	0/721 (0.00%)	0	1/2892 (0.03%)	1
Peritonsillar abscess * 1	0/734 (0.00%)	0	1/721 (0.14%)	1	0/2892 (0.00%)	0
Pneumonia * 1	1/734 (0.14%)	1	1/721 (0.14%)	1	1/2892 (0.03%)	1
Respiratory syncytial vrus bronchiolitis * 1	1/734 (0.14%)	1	1/721 (0.14%)	1	2/2892 (0.07%)	2
Respiratory syncytial vrus infection * 1	0/734 (0.00%)	0	0/721 (0.00%)	0	1/2892 (0.03%)	1
Staphylococcal abscess * 1	1/734 (0.14%)	1	0/721 (0.00%)	0	0/2892 (0.00%)	0
Staphylococcal infection * 1	0/734 (0.00%)	0	0/721 (0.00%)	0	1/2892 (0.03%)	1
Viral infection * 1	0/734 (0.00%)	0	0/721 (0.00%)	0	1/2892 (0.03%)	1
Viral upper respiratory tract infection * 1	0/734 (0.00%)	0	1/721 (0.14%)	1	1/2892 (0.03%)	1
Injury, poisoning and procedural complications
Accidental exposure * 1	0/734 (0.00%)	0	0/721 (0.00%)	0	1/2892 (0.03%)	10
Femur fracture * 1	0/734 (0.00%)	0	0/721 (0.00%)	0	2/2892 (0.07%)	2
Metabolism and nutrition disorders
Dehydration * 1	0/734 (0.00%)	0	0/721 (0.00%)	0	1/2892 (0.03%)	1
Hypovolaemia * 1	0/734 (0.00%)	0	0/721 (0.00%)	0	1/2892 (0.03%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Astrocytoma, low grade * 1	0/734 (0.00%)	0	0/721 (0.00%)	0	1/2892 (0.03%)	1
Nervous system disorders
Autism * 1	0/734 (0.00%)	0	0/721 (0.00%)	0	1/2892 (0.03%)	1
Febrile convulsion * 1	2/734 (0.27%)	2	3/721 (0.42%)	3	8/2892 (0.28%)	8
Seizure anoxic * 1	0/734 (0.00%)	0	0/721 (0.00%)	0	1/2892 (0.03%)	1
Psychiatric disorders
Affective disorder * 1	0/734 (0.00%)	0	1/721 (0.14%)	1	0/2892 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Adenoidal hypertrophy * 1	0/734 (0.00%)	0	1/721 (0.14%)	1	0/2892 (0.00%)	0
Asthma * 1	0/734 (0.00%)	0	0/721 (0.00%)	0	8/2892 (0.28%)	8
Bronchial hrperreactivity * 1	0/734 (0.00%)	0	1/721 (0.14%)	1	1/2892 (0.03%)	1
Respiratory arrest * 1	0/734 (0.00%)	0	0/721 (0.00%)	0	1/2892 (0.03%)	1
Status asthmaticus * 1	1/734 (0.14%)	1	0/721 (0.00%)	0	0/2892 (0.00%)	0
Vascular disorders
Kawasaki's disease * 1	0/734 (0.00%)	0	0/721 (0.00%)	0	3/2892 (0.10%)	3
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA, version 13.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5.00%
	Study Group 1 (Trivalent Influenza Vaccine)		Study Group 2 (Investigational Trivalent Influenza Vaccine)		Study Group 3 (Investigational Quadrivalent Influenza Vaccine)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	333/734 (45.37%)		329/721 (45.63%)		1358/2892 (46.96%)
Gastrointestinal disorders
Vomiting † 1	18/159 (11.32%)	18	20/144 (13.89%)	20	93/628 (14.81%)	93
Diarrhoea * 1	42/734 (5.72%)	51	38/721 (5.27%)	48	135/2892 (4.67%)	150
Vomiting * 1	46/734 (6.27%)	52	55/721 (7.63%)	61	193/2892 (6.67%)	209
General disorders
Injection site pain * 1	333/540 (61.67%)	333	329/547 (60.15%)	329	1358/2113 (64.27%)	1358
Injection site Swelling * 1	161/734 (21.93%)	162	154/692 (22.25%)	154	643/2742 (23.45%)	643
Malaise † 1	180/539 (33.40%)	180	181/546 (33.15%)	181	705/2110 (33.41%)	705
Injection site tenderness † 1	77/159 (48.43%)	77	72/145 (49.66%)	72	340/628 (54.14%)	340
Injection site erythema † 1	246/699 (35.19%)	246	238/692 (34.39%)	238	972/2742 (35.45%)	972
Fever † 1	75/695 (10.79%)	75	68/689 (9.87%)	68	276/2739 (10.08%)	276
Pyrexia * 1	44/734 (5.99%)	49	65/721 (9.02%)	75	188/2892 (6.50%)	213
Infections and infestations
Upper respiratory tract infection * 1	43/734 (5.86%)	51	47/721 (6.52%)	50	184/2892 (6.36%)	203
Metabolism and nutrition disorders
Appetite lost † 1	53/159 (33.33%)	53	36/144 (25.00%)	36	203/628 (32.32%)	203
Musculoskeletal and connective tissue disorders
Myalgia † 1	174/539 (32.28%)	174	190/546 (34.80%)	190	753/2110 (35.69%)	753
Nervous system disorders
Headache † 1	99/539 (18.37%)	99	115/546 (21.06%)	115	414/2110 (19.62%)	414
Drowsiness † 1	51/159 (32.08%)	51	46/144 (31.94%)	46	237/628 (37.74%)	237
Psychiatric disorders
Crying abnormal † 1	58/159 (36.48%)	58	43/144 (29.86%)	43	259/628 (41.24%)	259
Irritability † 1	84/159 (52.83%)	84	77/144 (53.47%)	77	339/628 (53.98%)	339
Respiratory, thoracic and mediastinal disorders
Cough * 1	95/734 (12.94%)	107	89/721 (12.34%)	100	341/2892 (11.79%)	381
Rhinorrhoea * 1	37/734 (5.04%)	38	34/721 (4.72%)	39	167/2892 (5.77%)	189
† Indicates events were collected by systematic assessment; * Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA, version 13.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Medical Director
• Organization: Sanofi Pasteur Inc.
• EMail: RegistryContactUs@sanofipasteur.com

Publications of Results:

Greenberg DP, Robertson CA, Landolfi VA, Bhaumik A, Senders SD, Decker MD. Safety and immunogenicity of an inactivated quadrivalent influenza vaccine in children 6 months through 8 years of age. Pediatr Infect Dis J. 2014 Jun;33(6):630-6. doi: 10.1097/INF.0000000000000254.

• Responsible Party: Sanofi ( Sanofi Pasteur, a Sanofi Company )
• ClinicalTrials.gov Identifier: NCT01240746
• Other Study ID Numbers: QIV04; UTN: U1111-1114-3713 ( Other Identifier: WHO )
• First Submitted: November 11, 2010
• First Posted: November 15, 2010
• Results First Submitted: July 3, 2013
• Results First Posted: January 14, 2014
• Last Update Posted: July 14, 2015