Evaluation of Responses to Fluzone® in Infants ≥ 6 Months of Age Who Did or Did Not Receive Fluzone® at 2 Months of Age

• ClinicalTrials.gov Identifier: NCT00885105
• Recruitment Status: Completed
• First Posted: April 21, 2009
• Results First Posted: January 1, 2010
• Last Update Posted: April 14, 2016
• Sponsor: Sanofi Pasteur, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: Influenza
• Intervention: Biological: Influenza Virus Vaccine
• Enrollment: 242

Participant Flow

Recruitment Details	Participants were enrolled from 17 October 2005 to 05 January 2006 at 7 medical centers in the US.
Pre-assignment Details	A total of 242 participants who met the inclusion and exclusion criteria were enrolled and vaccinated.

Arm/Group Title	Fluzone® Vaccine-Primed Group	Influenza Vaccine-Naive Group
Arm/Group Description	Participants had received 2 doses of Fluzone® vaccine at age 2 to 3 months; they received 2 doses of Fluzone® 2005-2006 pediatric formulation at age 6 to 11 months.	Participants had never previously received influenza vaccine, they received 2 doses of Fluzone® 2005-2006 pediatric formulation at age 6 to 11 months.
Period Title: Overall Study
Started	112	130
Completed	111	120
Not Completed	1	10
Reason Not Completed
Withdrawal by Subject	0	8
Adverse Event	1	0
Protocol Violation	0	2

Baseline Characteristics

Arm/Group Title		Fluzone® Vaccine-Primed Group	Influenza Vaccine-Naive Group	Total
Arm/Group Description		Participants had received 2 doses of Fluzone® vaccine at age 2 to 3 months; they received 2 doses of Fluzone® 2005-2006 pediatric formulation at age 6 to 11 months.	Participants had never previously received influenza vaccine, they received 2 doses of Fluzone® 2005-2006 pediatric formulation at age 6 to 11 months.	Total of all reporting groups
Overall Number of Baseline Participants		112	130	242
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	112 participants	130 participants	242 participants
	<=18 years	112 100.0%	130 100.0%	242 100.0%
	Between 18 and 65 years	0 0.0%	0 0.0%	0 0.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Months
	Number Analyzed	112 participants	130 participants	242 participants
		7.29 (1.1)	7.28 (1.47)	7.28 (1.3)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	112 participants	130 participants	242 participants
	Female	53 47.3%	60 46.2%	113 46.7%
	Male	59 52.7%	70 53.8%	129 53.3%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	112 participants	130 participants	242 participants
		112	130	242

Outcome Measures

1. Primary Outcome

Title	Summary of Influenza Seroprotection Post-vaccination With Fluzone® Vaccine.
Description	Seroprotection was defined as a Reciprocal Hemagglutination Inhibition Titers of ≥ 40 Post-vaccination with Fluzone® Vaccine.
Time Frame	Day 28 Post-vaccination

Outcome Measure Data

Analysis Population Description

Hemagglutination inhibition titers to the Influenza vaccine antigens were assessed in the per-protocol immunogenicity population.

Arm/Group Title	Fluzone® Vaccine-Primed Group	Influenza Vaccine-Naive Group
Arm/Group Description:	Participants had received 2 doses of Fluzone® vaccine at age 2 to 3 months; they received 2 doses of Fluzone® 2005-2006 pediatric formulation at age 6 to 11 months.	Participants had never previously received influenza vaccine, they received 2 doses of Fluzone® 2005-2006 pediatric formulation at age 6 to 11 months.
Overall Number of Participants Analyzed	51	51
Measure Type: Number; Unit of Measure: Percentage of Participants
A/New Caledonia/20/99 Post-Dose 1	44	34
A/New York/55/2004 Post-Dose 1	31	74
B/Jiangsu/310/2003 Post-Dose 1	22	6
A/New Caledonia/20/99 Post-Dose 2	69	86
A/New York/55/2004 Post-Dose 2	84	100
B/Jiangsu/310/2003 Post-Dose 2	28	47

2. Other Pre-specified Outcome

Title	Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Post-Vaccination With Fluzone® Vaccine.
Description	Antibodies against Influenza virus in Fluzone® Vaccine determined by the Hemagglutination inhibition (HAI) assay method.
Time Frame	Day 28 Post-vaccination

Outcome Measure Data

Analysis Population Description

Geometric Mean Titers to the Influenza vaccine antigens were assessed in the per-protocol immunogenicity population.

Arm/Group Title	Fluzone® Vaccine-Primed Group	Influenza Vaccine-Naive Group
Arm/Group Description:	Participants had received 2 doses of Fluzone® vaccine at age 2 to 3 months; they received 2 doses of Fluzone® 2005-2006 pediatric formulation at age 6 to 11 months.	Participants had never previously received influenza vaccine, they received 2 doses of Fluzone® 2005-2006 pediatric formulation at age 6 to 11 months.
Overall Number of Participants Analyzed	51	51
Geometric Mean (95% Confidence Interval); Unit of Measure: Titers
A/New Caledonia/20/99 Post-Dose 1	30.5; (22.3 to 41.8)	18.9; (14.1 to 25.4)
A/New York/55/2004 Post-Dose 1	21.4; (15.7 to 29.3)	65.6; (47.7 to 90.2)
B/Jiangsu/310/2003 Post-Dose 1	13.2; (9.89 to 17.6)	6.2; (5.27 to 7.29)
A/New Caledonia/20/99 Post-Dose 2	38.1; (29.6 to 49.2)	104; (77.1 to 139)
A/New York/55/2004 Post-Dose 2	78.9; (61.3 to 102)	277; (223 to 346)
B/Jiangsu/310/2003 Post-Dose 2	20.7; (16.1 to 26.6)	23.9; (18.2 to 31.3)

3. Other Pre-specified Outcome

Title	Geometric Mean Titers (GMTs) for Pertussis, Tetanus, Diphtheria, and Haemophilus Influenzae, Antigens Post-vaccination With Fluzone® Vaccine.
Description	Antibodies against Pertussis, Tetanus, and Haemophilus influenzae antigens were determined by an indirect Enzyme linked immunosorbent assay (ELISA). Anti-diphtheria antibody response was measured by the Vero Cells - diphtheria toxin challenge method. The serological determinations of total anti-PRP antibody was performed using a Farr-type radioimmunoassay.
Time Frame	Day 28 Post-vaccination

Outcome Measure Data

Analysis Population Description

GMTs to the Pertussis, Tetanus, Diphtheria and Haemophilus Influenzae antigens were assessed in the per-protocol immunogenicity population.

Arm/Group Title	Fluzone® Vaccine-Primed Group	Influenza Vaccine-Naive Group
Arm/Group Description:	Participants had received 2 doses of Fluzone® vaccine at age 2 to 3 months; they received 2 doses of Fluzone® 2005-2006 pediatric formulation at age 6 to 11 months.	Participants had never previously received influenza vaccine, they received 2 doses of Fluzone® 2005-2006 pediatric formulation at age 6 to 11 months.
Overall Number of Participants Analyzed	94	104
Geometric Mean (95% Confidence Interval); Unit of Measure: Titers
Pertussis Toxoid (EU/mL)	57.9; (47.9 to 69.9)	69.5; (57.6 to 83.7)
Filamentous Hemagglutinin (EU/mL)	37.3; (29.5 to 47.1)	47.3; (37.9 to 59.0)
Pertactin (EU/mL)	22.0; (16.8 to 28.8)	33.6; (26.1 to 43.2)
Fimbriae Types 2 and 3 (EU/mL)	26.7; (18.1 to 39.5)	11.6; (7.76 to 17.4)
Diphtheria (IU/mL)	0.230; (0.180 to 0.294)	0.251; (0.191 to 0.329)
Tetanus (IU/mL)	0.976; (0.694 to 1.37)	0.980; (0.720 to 1.33)

4. Other Pre-specified Outcome

Title	Geometric Mean Titers (GMTs) for Polyribosylribitol Phosphate and Pneumococcal Antibodies After Concomitant Vaccination With Fluzone® Vaccine.
Description	Human antibodies to Streptococcus pneumoniae (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) were determined by an Enzyme linked immunosorbent assay (ELISA).
Time Frame	Day 28 post-vaccination

Outcome Measure Data

Analysis Population Description

Geometric Mean Titers (GMTs) for Polyribosylribitol Phosphate and Pneumococcal antibodies were determined in the per-protocol population.

Arm/Group Title	Fluzone® Vaccine-Primed Group	Influenza Vaccine-Naive Group
Arm/Group Description:	Participants had received 2 doses of Fluzone® vaccine at age 2 to 3 months; they received 2 doses of Fluzone® 2005-2006 pediatric formulation at age 6 to 11 months.	Participants had never previously received influenza vaccine, they received 2 doses of Fluzone® 2005-2006 pediatric formulation at age 6 to 11 months.
Overall Number of Participants Analyzed	91	97
Geometric Mean (95% Confidence Interval); Unit of Measure: Titers
Polyribosylribitol Phosphate (mcg/mL)	1.69; (1.16 to 2.46)	2.12; (1.49 to 3.02)
Pneumococcal 4 (mcg/mL)	1.02; (0.854 to 1.22)	0.956; (0.781 to 1.17)
Pneumococcal 6B (mcg/mL)	1.14; (0.906 to 1.44)	1.24; (0.949 to 1.61)
Pneumococcal 9V (mcg/mL)	0.974; (0.812 to 1.17)	1.20; (0.981 to 1.46)
Pneumococcal 14 (mcg/mL)	4.98; (4.12 to 6.03)	5.54; (4.56 to 6.74)
Pneumococcal 18C (mcg/mL)	0.783; (0.646 to 0.950)	0.790; (0.644 to 0.970)
Pneumococcal 19F (mcg/mL)	1.49; (1.27 to 1.74)	1.26; (1.05 to 1.51)
Pneumococcal 23F (mcg/mL)	0.920; (0.737 to 1.15)	1.00; (0.779 to 1.29)

5. Other Pre-specified Outcome

Title	Geometric Mean Titers (GMTs) for Polio Antibodies After Concomitant Vaccination With Fluzone® Vaccine.
Description	Antibodies to polio viruses were measured by a serum neutralization assay.
Time Frame	Day 28 post-vaccination

Outcome Measure Data

Analysis Population Description

Geometric Mean Titers (GMTs) for the Polio antibodies were determined in the per-protocol population.

Arm/Group Title	Fluzone® Vaccine-Primed Group	Influenza Vaccine-Naive Group
Arm/Group Description:	Participants had received 2 doses of Fluzone® vaccine at age 2 to 3 months; they received 2 doses of Fluzone® 2005-2006 pediatric formulation at age 6 to 11 months.	Participants had never previously received influenza vaccine, they received 2 doses of Fluzone® 2005-2006 pediatric formulation at age 6 to 11 months.
Overall Number of Participants Analyzed	94	104
Geometric Mean (95% Confidence Interval); Unit of Measure: Titers
Polio Type 1 (1/dil)	555; (415 to 742)	1072; (814 to 1411)
Polio Type 2 (1/dil)	356; (268 to 474)	550; (411 to 736)
Polio Type 3 (1/dil)	394; (282 to 551)	571; (397 to 822)

6. Other Pre-specified Outcome

Title	Percentage of Participants With Solicited Injection Site and Systemic Reactions Post-vaccination With Fluzone® Vaccine.
Description	Solicited injection site reactions: Tenderness, erythema and swelling. Solicited systemic reactions: Fever (temperature), vomiting, abnormal crying, drowsiness, loss of appetite, and irritability.
Time Frame	Days 0 up to 7 post-vaccination

Outcome Measure Data

Analysis Population Description

Safety analysis was on all enrolled and vaccinated participants with available reaction data, intent-to-treat population

Arm/Group Title	Fluzone® Vaccine-Primed Group	Influenza Vaccine-Naive Group
Arm/Group Description:	Participants had received 2 doses of Fluzone® vaccine at age 2 to 3 months; they received 2 doses of Fluzone® 2005-2006 pediatric formulation at age 6 to 11 months.	Participants had never previously received influenza vaccine, they received 2 doses of Fluzone® 2005-2006 pediatric formulation at age 6 to 11 months.
Overall Number of Participants Analyzed	112	130
Measure Type: Number; Unit of Measure: Percentage of Participants
Any Solicited Injection Site Reaction Post-Dose 1	45	42
Any Tenderness	40	40
Grd 3 Tenderness (injected limb movement reduced)	1	1
Any Redness (> 0.5 cm)	11	14
Grade 3 Redness (≥ 5.0 cm)	2	1
Any Swelling (> 0.5 cm)	9	7
Grade 3 Swelling (≥ 5.0 cm)	1	0
Any Solicited Injection Site Reaction Post-Dose 2	36	34
Any Tenderness	34	28
Grd 3 Tenderness (injected limb movement reduced)	1	0
Any Redness (> 0.5 cm)	12	10
Grade 3 Redness ≥ 5.0 cm)	0	0
Any Swelling (> 0.5 cm)	10	5
Grade 3 Swelling (≥ 5.0 cm)	1	0
Any Solicited Injection Site Reaction - Any Dose	51	51
Any Tenderness	48	45
Grd 3 Tenderness (injected limb movement reduced)	2	1
Any Redness (> 0.5 cm)	16	19
Grade 3 Redness (≥ 5.0 cm)	2	1
Any Swelling (> 0.5 cm)	13	10
Grade 3 Swelling (≥ 5.0 cm)	1	0
Any Solicited Systemic Reaction Post-Dose 1	79	82
Any Fever	25	25
Grade 3 Fever ≥ 103.3 ºF)	0	1
Any Vomiting	14	7
Grade 3 Vomiting (≥ 6 episodes per 24 hours)	1	0
Any Abnormal Crying	46	32
Grade 3 Abnormal Crying (> 3 hours)	5	1
Any Drowsiness	47	45
Grade 3 Drowsiness (difficulty waking up)	1	1
Any Loss of Appetite	39	33
Grd 3 Loss of Appetite (refuses ≥ 3 or most feeds)	1	0
Any Irritability	65	63
Grade 3 Irritability (inconsolable)	2	1
Any Solicited Systemic Reaction Post-Dose 2	64	62
Any Fever	14	14
Grade 3 Fever (≥ 103.3 ºF)	1	2
Any Vomiting	8	12
Grade 3 Vomiting (≥ 6 episodes per 24 hours)	0	3
Any Abnormal Crying	39	26
Grade 3 Abnormal Crying (> 3 hours)	2	3
Any Drowsiness	29	34
Grade 3 Drowsiness (difficulty waking up)	0	1
Any Loss of Appetite	29	28
Grd 3 Loss of Appetite (refuses ≥ 3 or most feeds)	0	1
Any Irritability	56	43
Grade 3 Irritability (inconsolable)	3	3
Any Solicited Systemic Reaction - Any Dose	86	90
Any Fever	32	34
Grade 3 Fever (≥ 103.3 ºF)	1	2
Any Vomiting	20	16
Grade 3 Vomiting (≥ 6 episodes per 24 hours)	1	2
Any Abnormal Crying	55	45
Grade 3 Abnormal Crying (> 3 hours)	6	3
Any Drowsiness	53	53
Grade 3 Drowsiness (difficulty waking up)	1	2
Any Loss of Appetite	52	43
Grd 3 Loss of Appetite (refuses ≥ 3 or most feeds)	1	1
Any Irritability	76	71
Grade 3 Irritability (inconsolable)	4	2

Adverse Events

Time Frame	Adverse event data were collected over a period of 8 months. Six months post-vaccination 2
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Fluzone® Vaccine-Primed Group		Influenza Vaccine-Naive Group
Arm/Group Description	Participants had received 2 doses of Fluzone® vaccine at age 2 to 3 months; they received 2 doses of Fluzone® 2005-2006 pediatric formulation at age 6 to 11 months.		Participants had never previously received influenza vaccine, they received 2 doses of Fluzone® 2005-2006 pediatric formulation at age 6 to 11 months.
All-Cause Mortality
	Fluzone® Vaccine-Primed Group		Influenza Vaccine-Naive Group
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Fluzone® Vaccine-Primed Group		Influenza Vaccine-Naive Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/112 (4.46%)		1/130 (0.77%)
Congenital, familial and genetic disorders
Sickle cell anaemia with crisis * 1	0/112 (0.00%)	0	1/130 (0.77%)	3
Ear and labyrinth disorders
Deafness bilateral * 1	1/112 (0.89%)	1	0/130 (0.00%)	0
Infections and infestations
Bronchiolitis * 1	1/112 (0.89%)	1	0/130 (0.00%)	0
Gastroenteritis * 1	0/112 (0.00%)	0	1/130 (0.77%)	1
Gastroenteritis viral * 1	1/112 (0.89%)	1	0/130 (0.00%)	0
Pneumonia * 1	1/112 (0.89%)	1	1/130 (0.77%)	1
Pneumonia respiratory syncytial viral * 1	1/112 (0.89%)	1	0/130 (0.00%)	0
Metabolism and nutrition disorders
Dehydration * 1	1/112 (0.89%)	1	0/130 (0.00%)	0
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 7.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Fluzone® Vaccine-Primed Group		Influenza Vaccine-Naive Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	57/112 (50.89%)		56/130 (43.08%)
Eye disorders
Conjunctivitis * 1	5/112 (4.46%)	5	7/130 (5.38%)	9
General disorders
Pyrexia * 1	8/112 (7.14%)	8	6/130 (4.62%)	6
Infections and infestations
Bronchiolitis * 1	5/112 (4.46%)	5	8/130 (6.15%)	8
Croup infectious * 1	7/112 (6.25%)	7	2/130 (1.54%)	2
Otitis media * 1	30/112 (26.79%)	34	30/130 (23.08%)	31
Upper respiratory tract infection * 1	20/112 (17.86%)	21	24/130 (18.46%)	26
Respiratory, thoracic and mediastinal disorders
Cough * 1	7/112 (6.25%)	7	12/130 (9.23%)	13
Rhinorrhoea * 1	3/112 (2.68%)	3	8/130 (6.15%)	8
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 7.1

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: NCT00885105
• Other Study ID Numbers: GRC32
• First Submitted: April 20, 2009
• First Posted: April 21, 2009
• Results First Submitted: September 2, 2009
• Results First Posted: January 1, 2010
• Last Update Posted: April 14, 2016