Safety and Immunogenicity Testing of Influenza Vaccine in Healthy Children 2 Months and 6 Months of Age

• ClinicalTrials.gov Identifier: NCT00858468
• Recruitment Status: Completed
• First Posted: March 9, 2009
• Results First Posted: July 31, 2009
• 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: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: Influenza
• Intervention: Biological: Influenza virus vaccine (2004-2005 Formulation)
• Enrollment: 394

Participant Flow

Recruitment Details	Participants were enrolled from 08 April to 05 August 2005 in 8 medical centers in the US
Pre-assignment Details	A total of 394 participants that met the inclusion and exclusion criteria were enrolled, 393 were vaccinated.

Arm/Group Title	Age 6 to 12 Weeks	Age 24 to 36 Weeks
Arm/Group Description	Participants enrolled at 6 to 12 weeks of age	Participants enrolled at 24 to 36 weeks of age
Period Title: Overall Study
Started	201 [1]	192
Completed	201	192
Not Completed	0	0
[1] 1 enrolled participant was not vaccinated and removed from analysis

Baseline Characteristics

Arm/Group Title		Age 6 to 12 Weeks	Age 24 to 36 Weeks	Total
Arm/Group Description		Participants enrolled at 6 to 12 weeks of age	Participants enrolled at 24 to 36 weeks of age	Total of all reporting groups
Overall Number of Baseline Participants		201	192	393
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	201 participants	192 participants	393 participants
	<=18 years	201 100.0%	192 100.0%	393 100.0%
	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: Weeks
	Number Analyzed	201 participants	192 participants	393 participants
		9.4 (0.98)	27.0 (1.31)	18.0 (8.9)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	201 participants	192 participants	393 participants
	Female	98 48.8%	99 51.6%	197 50.1%
	Male	103 51.2%	93 48.4%	196 49.9%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	201 participants	192 participants	393 participants
		201	192	393

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation.
Description	Solicited local (injection site) reactions: Tenderness, erythema (redness), and swelling Solicited systemic reactions: Fever (Temperature), Vomiting, Crying abnormal, Drowsiness, Loss of Appetite, and Irritability.
Time Frame	Day 0 to Day 7 post-vaccination

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Age 6 to 12 Weeks	Age 24 to 36 Weeks
Arm/Group Description:	Participants enrolled at 6 to 12 weeks of age	Participants enrolled at 24 to 36 weeks of age
Overall Number of Participants Analyzed	201	192
Measure Type: Number; Unit of Measure: Percentage of participants
Any Solicited Injection Site Reaction - Dose 1	54	47
Any Tenderness	50	44
Grd 3 Tenderness-Inj. Limb movement reduced	6	2
Any Redness	11	7
Grade 3 Redness (≥ 5.0 cm)	0	0
Any Swelling	8	5
Grade 3 Swelling (≥ 5.0 cm)	0	0
Any Solicited Injection Site Reaction - Dose 2	41	27
Any Tenderness	38	26
Grd 3 Tenderness-Inj. Limb movement reduced	1	0
Any Redness	10	5
Grade 3 Redness (≥ 5.0 cm)	1	0
Any Swelling	5	2
Grade 3 Swelling (≥5.0 cm)	0	0
Any Solicited Injection Site Reaction - Any Doses	61	52
Any Tenderness	57	50
Grd 3 Tenderness-Inj. Limb movement reduced	7	2
Any Redness	16	10
Grade 3 Redness (≥ 5.0 cm)	1	0
Any Swelling	12	6
Grade 3 Swelling (≥ 5.0 cm)	0	0
Any Solicited Systemic Reaction Dose 1	90	82
Any Fever (Rectal Temp)	8	18
Grade 3 Fever (>39.5 ºC)	0	0
Any Vomiting	22	16
Grade 3 Vomiting (≥ 6 episodes per 24 hrs)	1	0
Any Abnormal Crying	59	45
Grade 3 Abnormal Crying	3	3
Any Drowsiness	72	50
Grade 3 Drowsiness (difficulty waking up)	2	1
Any Loss of Appetite	43	35
Grd 3 Loss of Appetite (refuses ≥ 3 meals)	0	2
Any Irritability	77	67
Grade 3 Irritability (inconsolable)	5	3
Any Solicited Systemic Reaction Dose 2	70	70
Any Fever (Rectal Temp)	4	14
Grade 3 Fever (>39.5 ºC)	0	2
Any Vomiting	14	8
Grade 3 Vomiting (≥ 6 episodes per 24 hrs)	1	0
Any Abnormal Crying	37	34
Grade 3 Abnormal Crying	4	1
Any Drowsiness	47	38
Grade 3 Drowsiness (difficulty waking up)	2	0
Any Loss of Appetite	28	27
Grade 3 Loss of Appetite (refuses ≥ 3 meals)	1	0
Any Irritability	55	53
Grade 3 Irritability (inconsolable)	3	1
Any Solicited Systemic Reaction Any Dose	92	89
Any Fever (Rectal Temp)	11	26
Grade 3 Fever (>39.5 ºC)	0	2
Any Vomiting	27	21
Grade 3 Vomiting (≥ 6 episodes per 24 hrs)	2	0
Any Abnormal Crying	66	55
Grade 3 Abnormal Crying	6	4
Any Drowsiness	78	58
Grade 3 Drowsiness (difficulty waking up)	4	1
Any Loss of Appetite	52	47
Grade 3 Loss of Appetite (refuses ≥ 3 meals)	1	2
Any Irritability	82	76
Grade 3 Irritability (inconsolable)	7	4

2. Other Pre-specified Outcome

Title	Percentage of Participants With Serum Hemagglutination Inhibition Antibody Titer ≥ 40 Post-vaccination With Fluzone® (Seroprotection).
Description	Data presented for each of the three influenza vaccine virus antigens in the Fluzone® 2004-2005 pediatric formulation. Seroprotection was defined as the percentage of participants with a reciprocal hemagglutination inhibition titers ≥ 40
Time Frame	21 days post-vaccination 2

Outcome Measure Data

Analysis Population Description

Seroprotection analysis was in all enrolled and vaccinated participants in the per-protocol immunogenicity population.

Arm/Group Title	Age 6 to 12 Weeks	Age 24 to 36 Weeks
Arm/Group Description:	Participants enrolled at 6 to 12 weeks of age	Participants enrolled at 24 to 36 weeks of age
Overall Number of Participants Analyzed	149	144
Measure Type: Number; Unit of Measure: Percentage of participants
A/NEW CALEDONIA/20/99 ≥ 40 Post-dose	46	69
A/WYOMING/03/2003 ≥ 40 Post-dose	59	78
B/JIANGSU/10/2003 ≥ 40 Post-dose	5	22

3. Other Pre-specified Outcome

Title	Percentage of Participants With a Pre-vaccination Serum Hemagglutination Inhibition Antibody Titer of ≤ 10 That Had a Titer of ≥ 40 Post-vaccination With Fluzone® (Seroconversion).
Description	Seroconversion was defined as the percentage of participants with a pre-titer < 1:10 who demonstrated a ≥ 4-fold increases in titer from pre- to post-vaccination.
Time Frame	21 days post-vaccination 2

Outcome Measure Data

Analysis Population Description

Seroconversion analysis was in all enrolled and vaccinated participants in the per-protocol immunogenicity population.

Arm/Group Title	Age 6 to 12 Weeks	Age 24 to 36 Weeks
Arm/Group Description:	Participants enrolled at 6 to 12 weeks of age	Participants enrolled at 24 to 36 weeks of age
Overall Number of Participants Analyzed	149	144
Measure Type: Number; Unit of Measure: Percentage of participants
A/NEW CALEDONIA/20/99, Pre-Dose ≤ 10	70	96
A/NEW CALEDONIA/20/99, Pre-Dose ≤10, Post-Dose ≥40	48	72
A/WYOMING/03/2003, Pre-Dose ≤ 10	32	74
A/WYOMING/03/2003, Pre-Dose ≤10, Post-Dose ≥40	60	86
FLU B/JIANGSU/10/2003, Pre-Dose ≤ 10	84	97
FLU B/JIANGSU/10/2003, Pre-Dose ≤10, Post-Dose ≥40	4	20

4. Other Pre-specified Outcome

Title	Geometric Mean Titers (GMTs) of Hemagglutination Antibodies Pre- and Post-vaccination With Fluzone® Vaccine.
Description	Data presented for each of the three influenza vaccine virus antigens in the Fluzone® 2004-2005 pediatric formulation.
Time Frame	21 days post-vaccination 2

Outcome Measure Data

Analysis Population Description

GMTs were assessed on the Per-Protocol Population

Arm/Group Title	Age 6 to 12 Weeks	Age 24 to 36 Weeks
Arm/Group Description:	Participants enrolled at 6 to 12 weeks of age	Participants enrolled at 24 to 36 weeks of age
Overall Number of Participants Analyzed	149	144
Geometric Mean (95% Confidence Interval); Unit of Measure: Titers
A/NEW CALEDONIA/20/99 Pre-dose	11.5; (9.4 to 14.1)	5.7; (5.3 to 6.0)
A/NEW CALEDONIA/20/99 Post-dose	27.6; (23.1 to 33.1)	47.0; (39.3 to 56.2)
A/WYOMING/03/2003 Pre-dose	40.8; (31.2 to 53.2)	9.8; (8.1 to 11.9)
A/WYOMING/03/2003 Post-dose	46.3; (38.7 to 55.4)	90.9; (72.2 to 114.4)
B/JIANGSU/10/2003 Pre-dose	7.0; (6.3 to 7.8)	5.4; (5.1 to 5.7)
B/JIANGSU/10/2003 Post-dose	8.4; (7.5 to 9.3)	15.3; (12.9 to 18.2)

Adverse Events

Time Frame	Adverse event data were collected for 6 months post-vaccination.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Age 6 to 12 Weeks		Age 24 to 36 Weeks
Arm/Group Description	Participants enrolled at 6 to 12 weeks of age		Participants enrolled at 24 to 36 weeks of age
All-Cause Mortality
	Age 6 to 12 Weeks		Age 24 to 36 Weeks
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Age 6 to 12 Weeks		Age 24 to 36 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/201 (1.99%)		3/192 (1.56%)
Gastrointestinal disorders
Viral gastroenteritis * 1	0/201 (0.00%)	0	1/192 (0.52%)	1
Infections and infestations
Kawasaki's disease * 1	1/201 (0.50%)	1	0/192 (0.00%)	0
Cellulitis * 1	0/201 (0.00%)	0	1/192 (0.52%)	1
Fever * 1	1/201 (0.50%)	1	0/192 (0.00%)	0
Nervous system disorders
Febrile convulsion * 1	0/201 (0.00%)	0	1/192 (0.52%)	3
Respiratory, thoracic and mediastinal disorders
Choking * 1	1/201 (0.50%)	1	0/192 (0.00%)	0
Bronchiolitis * 1	1/201 (0.50%)	1	0/192 (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	5.0%
	Age 6 to 12 Weeks		Age 24 to 36 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	54/201 (26.87%)		94/192 (48.96%)
Gastrointestinal disorders
Diarrhoea * 1	10/201 (4.98%)	11	12/192 (6.25%)	13
Teething * 1	0/201 (0.00%)	0	17/192 (8.85%)	22
General disorders
Injection site haemorrhage * 1	4/201 (1.99%)	5	10/192 (5.21%)	11
Pyrexia * 1	5/201 (2.49%)	6	19/192 (9.90%)	20
Infections and infestations
Nasopharyngitis * 1	2/201 (1.00%)	2	11/192 (5.73%)	12
Otitis media * 1	3/201 (1.49%)	3	16/192 (8.33%)	18
Upper respiratory tract infection * 1	13/201 (6.47%)	13	19/192 (9.90%)	20
Respiratory, thoracic and mediastinal disorders
Cough * 1	8/201 (3.98%)	8	16/192 (8.33%)	17
Nasal congestion * 1	13/201 (6.47%)	14	3/192 (1.56%)	3
Rhinorrhoea * 1	9/201 (4.48%)	10	15/192 (7.81%)	17
Skin and subcutaneous tissue disorders
Rash * 1	4/201 (1.99%)	5	10/192 (5.21%)	11
* 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: NCT00858468
• Other Study ID Numbers: GRC27
• First Submitted: March 5, 2009
• First Posted: March 9, 2009
• Results First Submitted: April 20, 2009
• Results First Posted: July 31, 2009
• Last Update Posted: April 14, 2016