Study of Fluzone® Quadrivalent, Fluzone® Intradermal, and Fluzone® High-Dose, Influenza Vaccines in Adults

• ClinicalTrials.gov Identifier: NCT02258334
• Recruitment Status: Completed
• First Posted: October 7, 2014
• Results First Posted: October 19, 2015
• Last Update Posted: October 19, 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: None (Open Label); Primary Purpose: Prevention
• Condition: Influenza
• Interventions: Biological: Fluzone® Quadrivalent vaccine, 2014-2015 formulation; Biological: Fluzone I®ntradermal vaccine, 2014-2015 formulation; Biological: Fluzone High Dose vaccine, 2014-2015 formulation
• Enrollment: 208

Participant Flow

Recruitment Details	Study participants were enrolled from 01 October 2014 to 07 November 2014 at 4 clinical sites in the United States.
Pre-assignment Details	A total of 208 participants who met all of the inclusion criteria and none of the exclusion criteria were enrolled and vaccinated in this study.

Arm/Group Title	Group 1	Group 2	Group 3	Group 4
Arm/Group Description	Adults 18 to < 65 years of age randomly assigned to receive an intramuscular dose of Fluzone Quadrivalent vaccine.	Adults 18 to < 65 years of age randomly assigned to receive an intradermal dose of Fluzone Intradermal vaccine.	Adults ≥65 years of age randomly assigned to receive an intramuscular dose of Fluzone Quadrivalent vaccine.	Adults ≥65 years of age randomly assigned to receive an intramuscular dose of Fluzone High-Dose vaccine.
Period Title: Overall Study
Started	50	54	52	52
Completed	49	54	52	52
Not Completed	1	0	0	0
Reason Not Completed
Adverse Event	1	0	0	0

Baseline Characteristics

Arm/Group Title		Group 1	Group 2	Group 3	Group 4	Total
Arm/Group Description		Adults 18 to < 65 years of age randomly assigned to receive an intramuscular dose of Fluzone Quadrivalent vaccine.	Adults 18 to < 65 years of age randomly assigned to receive an intradermal dose of Fluzone Intradermal vaccine.	Adults ≥ 65 years of age randomly assigned to receive an intramuscular dose of Fluzone Quadrivalent vaccine.	Adults ≥ 65 years of age randomly assigned to receive an intramuscular dose of Fluzone High-Dose vaccine.	Total of all reporting groups
Overall Number of Baseline Participants		50	54	52	52	208
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	50 participants	54 participants	52 participants	52 participants	208 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	50 100.0%	54 100.0%	0 0.0%	0 0.0%	104 50.0%
	>=65 years	0 0.0%	0 0.0%	52 100.0%	52 100.0%	104 50.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
Age Continuous	Number Analyzed	50 participants	54 participants	52 participants	52 participants	208 participants
		44.8 (14.9)	48.0 (12.1)	73.9 (5.0)	72.2 (5.4)	59.8 (16.8)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	50 participants	54 participants	52 participants	52 participants	208 participants
	Female	31 62.0%	33 61.1%	32 61.5%	31 59.6%	127 61.1%
	Male	19 38.0%	21 38.9%	20 38.5%	21 40.4%	81 38.9%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	50 participants	54 participants	52 participants	52 participants	208 participants
		50	54	52	52	208

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Reporting Solicited Injection-site and Solicited Systemic Reactions Following Vaccination With the 2014-2015 Formulation of Fluzone® Quadrivalent or Fluzone® Intradermal or Fluzone® High-Dose Vaccine
Description	Injection-site reactions: Pain, Erythema, Swelling, Induration, and Ecchymosis. Systemic reactions: Fever (Temperature), Headache, Malaise, Myalgia, and Shivering. Grade 3 Injection-site reactions: Pain, Significant, prevents daily activity; Erythema, Swelling, Induration, and Ecchymosis, >100 mm. Grade 3 Systemic reactions: Fever, ≥39.0°C or ≥102.1°F; Headache, Malaise, Myalgia, and Shivering, Significant, prevents daily activity.
Time Frame	Day 0 up to Day 7 post-vaccination

Outcome Measure Data

Analysis Population Description

Solicited injection-site and systemic reactions were assessed in the Safety Analysis Set.

Arm/Group Title	Group 1	Group 2	Group 3	Group 4
Arm/Group Description:	Adults 18 to < 65 years of age randomly assigned to receive an intramuscular dose of Fluzone Quadrivalent vaccine.	Adults 18 to < 65 years of age randomly assigned to receive an intradermal dose of Fluzone Intradermal vaccine.	Adults ≥65 years of age randomly assigned to receive an intramuscular dose of Fluzone Quadrivalent vaccine.	Adults ≥65 years of age randomly assigned to receive an intramuscular dose of Fluzone High-Dose vaccine.
Overall Number of Participants Analyzed	49	54	52	52
Measure Type: Number; Unit of Measure: Percentage of participants
Injection-site Pain	53.1	51.9	36.5	40.4
Grade 3 Injection-site Pain	0.0	1.9	0	0
Injection-site Erythema	6.1	35.2	3.8	7.7
Grade 3 Injection site Erythema	0.0	0	0	0
Injection-site Swelling	4.1	22.2	5.8	5.8
Grade 3 Injection-site Swelling	0.0	0	0	0
Injection-site Induration	6.1	18.5	0	1.9
Grade 3 Injection-site Induration	0.0	0	0	0
Injection-site Ecchymosis	2.0	5.6	0	1.9
Grade 3 Injection-site Ecchymosis	0.0	0	0	0
Fever	0.0	0	0	0
Grade 3 Fever	0.0	0	0	0
Headache	28.6	18.5	17.3	25.0
Grade 3 Headache	0.0	0	0	1.9
Malaise	16.3	27.8	9.6	15.4
Grade 3 Malaise	0.0	1.9	0	1.9
Myalgia	26.5	25.9	23.1	28.8
Grade 3 Myalgia	0.0	1.9	1.9	1.9
Shivering	4.1	9.3	1.9	1.9
Grade 3 Shivering	0.0	0	0	0

2. Secondary Outcome

Title	Geometric Mean Titers (GMTs) of Antibodies to the 2014-2015 Formulation of Fluzone® Quadrivalent or Fluzone® Intradermal or Fluzone® High-Dose Vaccine Antigens Before and Following Vaccination With the Respective Vaccine.
Description	Geometric mean titers of antibodies to Fluzone® Quadrivalent, Fluzone® Intradermal, and Fluzone® High-Dose vaccine antigens were assessed using the hemagglutination inhibition (HAI) assay.
Time Frame	Day 0 (pre-vaccination) and Day 21 post-vaccination

Outcome Measure Data

Analysis Population Description

Geometric mean titers were assessed in the Per-Protocol Analysis Set.

Arm/Group Title	Group 1	Group 2	Group 3	Group 4
Arm/Group Description:	Adults 18 to < 65 years of age randomly assigned to receive an intramuscular dose of Fluzone Quadrivalent vaccine.	Adults 18 to < 65 years of age randomly assigned to receive an intradermal dose of Fluzone Intradermal vaccine.	Adults ≥65 years of age randomly assigned to receive an intramuscular dose of Fluzone Quadrivalent vaccine.	Adults ≥65 years of age randomly assigned to receive an intramuscular dose of Fluzone High-Dose vaccine.
Overall Number of Participants Analyzed	49	53	52	52
Geometric Mean (95% Confidence Interval); Unit of Measure: Titers (1/dilution)
A/H1N1; Pre-vaccination (N=49,52,52,52)	153; (90.6 to 260)	148; (94.3 to 231)	148; (96.7 to 226)	171; (124 to 237)
A/H1N1; Post-vaccination (N=49,53,52,52)	707; (490 to 1020)	632; (459 to 870)	288; (200 to 414)	386; (294 to 506)
A/H3N2; Pre-vaccination (N=49,53,52,52)	139; (90.9 to 212)	147; (97.6 to 221)	168; (119 to 237)	275; (193 to 390)
A/H3N2; Post-vaccination (N=49,53,52,52)	613; (439 to 857)	648; (470 to 894)	349; (244 to 499)	680; (490 to 942)
B (Yamagata); Pre-vaccination (N=49,53,52,52)	596; (400 to 888)	471; (324 to 684)	471; (342 to 649)	465; (340 to 635)
B (Yamagata); Post-vaccination (N=49,53,52,52)	1836; (1376 to 2449)	1272; (906 to 1785)	864; (651 to 1146)	994; (777 to 1270)
B (Victoria); Pre-vaccination (N=49,0,52,0)	252; (164 to 385)	NA [1]; (NA to NA)	273; (195 to 382)	NA [1]; (NA to NA)
B (Victoria); Post-vaccination (N=49,0,52,0)	1119; (838 to 1495)	NA [1]; (NA to NA)	568; (430 to 750)	NA [1]; (NA to NA)

[1]

B (Victoria) antigen was not in the administered vaccine

3. Secondary Outcome

Title	Percentage of Participants With Seroprotection Before and Following Vaccination With the 2014-2015 Formulation of Fluzone® Quadrivalent or Fluzone® Intradermal or Fluzone® High-Dose Vaccine.
Description	Antibodies to Fluzone® Quadrivalent, Fluzone® Intradermal, and Fluzone® High-Dose vaccine antigens were assessed using the hemagglutination inhibition (HAI) assay. Seroprotection was defined as a titer ≥40 (l/dilution [dil]) at pre-vaccination and 21 days after vaccination.
Time Frame	Day 0 (pre-vaccination) and Day 21 post-vaccination

Outcome Measure Data

Analysis Population Description

Seroprotection was assessed in the Per-Protocol Analysis Set.

Arm/Group Title	Group 1	Group 2	Group 3	Group 4
Arm/Group Description:	Adults 18 to < 65 years of age randomly assigned to receive an intramuscular dose of Fluzone Quadrivalent vaccine.	Adults 18 to < 65 years of age randomly assigned to receive an intradermal of Fluzone Intradermal vaccine.	Adults ≥65 years of age randomly assigned to receive an intramuscular dose of Fluzone Quadrivalent vaccine.	Adults ≥65 years of age randomly assigned to receive an intramuscular dose of Fluzone High-Dose vaccine.
Overall Number of Participants Analyzed	49	53	52	52
Measure Type: Number; Unit of Measure: Percentage of participants
A/H1N1; Pre-vaccination (N=49,52,52,52)	77.6	84.6	82.7	90.4
A/H1N1; Post-vaccination (N=49,53,52,52)	98.0	100.0	92.3	100.0
A/H3N2; Pre-vaccination (N=49,53,52,52)	81.6	83.0	90.4	96.2
A/H3N2; Post-vaccination (N=49,53,52,52)	98.0	100.0	94.2	100.0
B (Yamagata); Pre-vaccination (N=49,53,52,52)	98.0	98.1	96.2	100.0
B (Yamagata); Post-vaccination (N=49,53,52,52)	100.0	100.0	100.0	100.0
B (Victoria); Pre-vaccination (n=49,0,52,0)	91.8	NA [1]	94.2	NA [1]
B (Victoria); Post-vaccination (N=49,0,52,0)	100.0	NA [1]	100.0	NA [1]

[1]

B (Victoria) antigen was not in the administered vaccine

4. Secondary Outcome

Title	Percentage of Participants With Seroconversion Following Vaccination With the 2014-2015 Formulation of Fluzone® Quadrivalent or Fluzone® Intradermal or Fluzone® High-Dose Vaccine
Description	Antibodies to Fluzone® Quadrivalent, Fluzone® Intradermal, and Fluzone® High-Dose vaccine antigens were assessed using the hemagglutination inhibition (HAI) assay. Seroconversion was defined as either a pre-vaccination titer < 10 (1/dil) and a post-vaccination titer ≥ 40 (1/dil) or a pre-vaccination titer ≥ 10 (1/dil) and a ≥ 4-fold increase in post-vaccination titer 21 days after vaccination.
Time Frame	Day 21 post-vaccination

Outcome Measure Data

Analysis Population Description

Seroconversion was assessed in the Per-Protocol Analysis Set.

Arm/Group Title	Group 1	Group 2	Group 3	Group 4
Arm/Group Description:	Adults 18 to < 65 years of age randomly assigned to receive an intramuscular dose of Fluzone Quadrivalent vaccine.	Adults 18 to < 65 years of age randomly assigned to receive an intradermal dose of Fluzone Intradermal vaccine.	Adults ≥65 years of age randomly assigned to receive an intramuscular dose of Fluzone Quadrivalent vaccine.	Adults ≥65 years of age randomly assigned to receive an intramuscular dose of Fluzone High Dose vaccine.
Overall Number of Participants Analyzed	49	53	52	52
Measure Type: Number; Unit of Measure: Percentage of participants
A/H1N1 (N=49,52,52,52)	34.7	42.3	15.4	28.8
A/H3N2 (N=49,53,52,52)	38.8	39.6	23.1	26.9
B (Yamagata) (N=49,53,52,52)	28.6	28.3	15.4	21.2
B (Victoria) (N=49,0,52,0)	51.0	NA [1]	23.1	NA [1]

[1]

B (Victoria) antigen was not in the administered vaccine

5. Secondary Outcome

Title	Geometric Mean Titer Ratios (GMTRs) of Antibodies to the 2014-2015 Formulation of Fluzone® Quadrivalent or Fluzone® Intradermal or Fluzone® High-Dose Vaccine Antigens Following Vaccination With the Respective Vaccine
Description	Geometric mean titer ratios of antibodies to Fluzone® Quadrivalent, Fluzone® Intradermal, and Fluzone® High-Dose vaccine antigens were assessed using the hemagglutination inhibition (HAI) assay.
Time Frame	Day 21 post-vaccination

Outcome Measure Data

Analysis Population Description

Geometric mean titer ratios were assessed in the Per-Protocol Analysis Set.

Arm/Group Title	Group 1	Group 2	Group 3	Group 4
Arm/Group Description:	Adults 18 to < 65 years of age randomly assigned to receive an intramuscular dose of Fluzone Quadrivalent vaccine.	Adults 18 to < 65 years of age randomly assigned to receive an intradermal dose of Fluzone Intradermal vaccine.	Adults ≥65 years of age randomly assigned to receive an intramuscular dose of Fluzone Quadrivalent vaccine.	Adults ≥65 years of age randomly assigned to receive an intramuscular dose of Fluzone High Dose vaccine.
Overall Number of Participants Analyzed	49	53	52	52
Geometric Mean (95% Confidence Interval); Unit of Measure: Titer ratios
A/H1N1 (N=49,52,52,52)	4.32; (2.66 to 7.04)	3.92; (2.54 to 6.06)	1.91; (1.53 to 2.38)	2.25; (1.79 to 2.83)
A/H3N2 (N=49,53,52,52)	4.26; (2.83 to 6.42)	4.24; (2.93 to 6.14)	2.08; (1.65 to 2.62)	2.48; (1.97 to 3.12)
B (Yamagata) (N=49,53,52,52)	3.08; (2.21 to 4.29)	2.70; (1.95 to 3.74)	1.83; (1.48 to 2.28)	2.14; (1.72 to 2.65)
B (Victoria) (N=49,0,52,0)	4.39; (3.05 to 6.30)	NA [1]; (NA to NA)	2.08; (1.62 to 2.68)	NA [1]; (NA to NA)

[1]

B (Victoria) antigen was not in the administered vaccine

Adverse Events

Time Frame	Adverse event data were collected from Day 0 (post-vaccination) up to Day 21 post-vaccination.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Group 1		Group 2		Group 3		Group 4
Arm/Group Description	Adults 18 to < 65 years of age randomly assigned to receive an intramuscular dose of Fluzone Quadrivalent vaccine.		Adults 18 to < 65 years of age randomly assigned to receive an intradermal dose of Fluzone Intradermal vaccine.		Adults ≥65 years of age randomly assigned to receive an intramuscular dose of Fluzone Quadrivalent vaccine.		Adults ≥65 years of age randomly assigned to receive an intramuscular dose of Fluzone High Dose vaccine.
All-Cause Mortality
	Group 1		Group 2		Group 3		Group 4
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--		--/--
Serious Adverse Events
	Group 1		Group 2		Group 3		Group 4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/49 (0.00%)		0/54 (0.00%)		1/52 (1.92%)		0/52 (0.00%)
Gastrointestinal disorders
Haematochezia * 1	0/49 (0.00%)	0	0/54 (0.00%)	0	1/52 (1.92%)	1	0/52 (0.00%)	0
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 16.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5.00%
	Group 1		Group 2		Group 3		Group 4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/49 (53.06%)		28/54 (51.85%)		19/52 (36.54%)		21/52 (40.38%)
General disorders
Injection site Pain † 1	26/49 (53.06%)	26	28/54 (51.85%)	28	19/52 (36.54%)	19	21/52 (40.38%)	21
Injection site Erythema † 1	3/49 (6.12%)	3	19/54 (35.19%)	19	2/52 (3.85%)	2	4/52 (7.69%)	4
Injection site Swelling † 1	2/49 (4.08%)	2	12/54 (22.22%)	12	3/52 (5.77%)	3	3/52 (5.77%)	3
Injection site Induration † 1	3/49 (6.12%)	3	10/54 (18.52%)	10	0/52 (0.00%)	0	1/52 (1.92%)	1
Injection site Ecchymosis † 1	1/49 (2.04%)	1	3/54 (5.56%)	3	0/52 (0.00%)	0	1/52 (1.92%)	1
Malaise † 1	8/49 (16.33%)	8	15/54 (27.78%)	15	5/52 (9.62%)	5	8/52 (15.38%)	8
Shivering † 1	2/49 (4.08%)	2	5/54 (9.26%)	5	1/52 (1.92%)	1	1/52 (1.92%)	1
Musculoskeletal and connective tissue disorders
Myalgia † 1	13/49 (26.53%)	13	14/54 (25.93%)	14	12/52 (23.08%)	12	15/52 (28.85%)	15
Nervous system disorders
Headache † 1	14/49 (28.57%)	14	10/54 (18.52%)	10	9/52 (17.31%)	9	13/52 (25.00%)	13
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 16.0

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

• Responsible Party: Sanofi ( Sanofi Pasteur, a Sanofi Company )
• ClinicalTrials.gov Identifier: NCT02258334
• Other Study ID Numbers: GRC55; U1111-1143-8931 ( Other Identifier: WHO )
• First Submitted: October 2, 2014
• First Posted: October 7, 2014
• Results First Submitted: September 16, 2015
• Results First Posted: October 19, 2015
• Last Update Posted: October 19, 2015