Safety and Immunogenicity of Fluzone® Vaccine in Children Who Received 2 Doses of the 2005-2006 Fluzone Formulation.

• ClinicalTrials.gov Identifier: NCT00390884
• Recruitment Status: Completed
• First Posted: October 23, 2006
• Results First Posted: December 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: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: Influenza
• Intervention: Biological: Influenza Virus Vaccine, Fluzone®
• Enrollment: 173

Participant Flow

Recruitment Details	Participants were enrolled into this study from 03 October 2006 to 04 January 2007 at 5 US clinical centers.
Pre-assignment Details	A total of 173 participants were enrolled, vaccinated, and analyzed.

Arm/Group Title	Fluzone®-Primed Group	Fluzone®-Naive Group
Arm/Group Description	Participants had received two doses of the 2005-2006 formulation of Fluzone® vaccine in the fall of 2005 (Study GRC28 NCT00242424); they received two doses of Fluzone® Pediatric 2006-2007 formulation.	Participants had never received influenza vaccine and had received two doses of placebo (Study GRC28 NCT00242424); they received two doses of Fluzone® Pediatric 2006-2007 formulation.
Period Title: Overall Study
Started	116	57
Completed	114	55
Not Completed	2	2
Reason Not Completed
Withdrawal by Subject	2	2

Baseline Characteristics

Arm/Group Title		Fluzone®-Primed Group	Fluzone®-Naive Group	Total
Arm/Group Description		Participants had received two doses of the 2005-2006 formulation of Fluzone® vaccine in the fall of 2005 (Study GRC28 NCT00242424); they received two doses of Fluzone® Pediatric 2006-2007 formulation.	Participants had never received influenza vaccine and had received two doses of placebo (Study GRC28 NCT00242424); they received two doses of Fluzone® Pediatric 2006-2007 formulation.	Total of all reporting groups
Overall Number of Baseline Participants		116	57	173
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	116 participants	57 participants	173 participants
	<=18 years	116 100.0%	57 100.0%	173 100.0%
	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	116 participants	57 participants	173 participants
		13.8 (1.01)	13.9 (1.13)	13.8 (1.07)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	116 participants	57 participants	173 participants
	Female	48 41.4%	22 38.6%	70 40.5%
	Male	68 58.6%	35 61.4%	103 59.5%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	116 participants	57 participants	173 participants
		116	57	173

Outcome Measures

1. Primary Outcome

Title	Percentage of Seroprotected Participants Post-vaccination With Fluzone®
Description	Seroprotection was defined as a Post-vaccination Hemagglutination Inhibition titer of greater than or equal to 1:40.
Time Frame	Day 28 Post-vaccination

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Fluzone®-Primed Group	Fluzone®-Naive Group
Arm/Group Description:	Participants had received two doses of the 2005-2006 formulation of Fluzone® vaccine in the fall of 2005 (Study GRC28 NCT00242424); they received two doses of Fluzone® Pediatric 2006-2007 formulation.	Participants had never received influenza vaccine and had received two doses of placebo (Study GRC28 NCT00242424); they received two doses of Fluzone® Pediatric 2006-2007 formulation.
Overall Number of Participants Analyzed	94	50
Measure Type: Number; Unit of Measure: Percentage of Participants
Flu A/New Caledonia/20/99 (H1N1) Post-Dose 1	59	34
Flu A/Wisconsin/67/2005 (H3N2) Post -Dose 1	95	80
Flu B/Malaysia/2506/2004 Post-Dose 1	10	6
Flu A/New Caledonia/20/99 (H1N1) Post-Dose 2	62	82
Flu A/Wisconsin/67/2005 (H3N2) Post -Dose 2	79	94
Flu B/Malaysia/2506/2004 Post-Dose 2	50	65

2. Secondary Outcome

Title	Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibodies Post-vaccination With Fluzone®
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

The Geometric Mean Titers were analyzed in the per-protocol immunogenicity population

Arm/Group Title	Fluzone®-Primed Group	Fluzone®-Naive Group
Arm/Group Description:	Participants had received two doses of the 2005-2006 formulation of Fluzone® vaccine in the fall of 2005 (Study GRC28 NCT00242424); they received two doses of Fluzone® Pediatric 2006-2007 formulation.	Participants had never received influenza vaccine and had received two doses of placebo (Study GRC28 NCT00242424); they received two doses of Fluzone® Pediatric 2006-2007 formulation.
Overall Number of Participants Analyzed	94	50
Geometric Mean (95% Confidence Interval); Unit of Measure: Titers
Flu A/New Caledonia/20/99 (H1N1) Post-Dose 1	41.3; (32.9 to 52.0)	22.7; (17.9 to 28.7)
Flu A/Wisconsin/67/2005 (H3N2) Post-Dose 1	144; (116 to 179)	89.4; (55.4 to 144)
Flu B/Malaysia/2506/2004 Post-Dose 1	11.1; (8.45 to 14.6)	9.27; (6.31 to 13.6)
Flu A/New Caledonia/20/99 (H1N1) Post-Dose 2	42.1; (27.3 to 64.8)	78.4; (47.1 to 131)
Flu A/Wisconsin/67/2005 (H3N2) Post-Dose 2	103; (68.9 to 155)	217; (122 to 388)
Flu B/Malaysia/2506/2004 Post-Dose 2	39.2; (25.5 to 60.3)	63.9; (34.9 to 117)

3. Other Pre-specified Outcome

Title	Percentage of Participants With At Least One Solicited Injection Site or Systemic Reaction Post-vaccination With Fluzone®
Description	Solicited injection site: tenderness, erythema, and swelling; Solicited systemic reactions: fever, vomiting, abnormal crying, drowsiness, appetite loss, and irritability, after each vaccination
Time Frame	Days 0-7 Post-vaccination

Outcome Measure Data

Analysis Population Description

The safety analysis was on all enrolled and vaccinated participants, intent-to-treat population.

Arm/Group Title	Fluzone®-Primed Group	Fluzone®-Naive Group
Arm/Group Description:	Participants had received two doses of the 2005-2006 formulation of Fluzone® vaccine in the fall of 2005 (Study GRC28 NCT00242424); they received two doses of Fluzone® Pediatric 2006-2007 formulation.	Participants had never received influenza vaccine and had received two doses of placebo (Study GRC28 NCT00242424); they received two doses of Fluzone® Pediatric 2006-2007 formulation.
Overall Number of Participants Analyzed	116	57
Measure Type: Number; Unit of Measure: Percentage of Participants
Any Injection Site Reaction Post-Dose 1	51	55
Any Tenderness	46	55
Grade 3 Tenderness (Crying when limb is moved)	0	0
Any Redness (> 0.5 cm)	7	7
Grade 3 Redness (≥ 5.0 cm)	0	0
Any Swelling (> 0.5 cm)	5	7
Grade 3 Swelling (≥ 5.0 cm)	0	0
Any Injection Site Reaction Post-Dose 2	57	51
Any Tenderness	56	49
Grade 3 Tenderness (Crying when limb is moved)	1	0
Any Redness (> 0.5 cm)	7	6
Grade 3 Redness (≥ 5.0 cm)	0	0
Any Swelling (> 0.5 cm)	4	0
Grade 3 Swelling (≥ 5.0 cm)	0	0
Any Injection Site Reaction - Any Dose	68	69
Any Tenderness	65	69
Grade 3 Tenderness (Crying when limb is moved)	1	0
Any Redness (> 0.5 cm)	13	11
Grade 3 Redness (≥ 5.0 cm)	0	0
Any Swelling (> 0.5 cm)	6	7
Grade 3 Swelling (≥ 5.0 cm)	0	0
Any Systemic Reaction Post-Dose 1	75	76
Any Fever	16	11
Grade 3 Fever (≥ 103.2 ºF)	0	0
Any Vomiting	13	16
Grade 3 Vomiting (≥ 6 episodes per 24 hours)	0	0
Any Abnormal Crying	42	36
Grade 3 Abnormal Crying (> 3 hours)	0	0
Any Drowsiness	32	31
Grade 3 Drowsiness (Slept most of time)	0	2
Any Loss of Appetite	38	33
Grade 3 Loss of Appetite (Refuses ≥ 3 feeds)	2	2
Any Irritability	66	64
Grade 3 Irritability (Inconsolable)	2	0
Any Systemic Reaction Post-Dose 2	72	71
Any Fever	17	15
Grade 3 Fever (≥ 103.2 ºF)	2	2
Any Vomiting	12	16
Grade 3 Vomiting (≥ 6 episodes per 24 hours)	2	0
Any Abnormal Crying	39	33
Grade 3 Abnormal Crying (> 3 hours)	3	0
Any Drowsiness	32	33
Grade 3 Drowsiness (Slept most of time)	1	0
Any Loss of Appetite	32	33
Grade 3 Loss of Appetite (Refuses ≥ 3 feeds)	5	0
Any Irritability	57	60
Grade 3 Irritability (Inconsolable)	4	0
Any Systemic Reaction - Any Dose	88	89
Any Fever	29	24
Grade 3 Fever (≥ 103.2 ºF)	2	2
Any Vomiting	21	29
Grade 3 Vomiting (≥ 6 episodes per 24 hours)	2	0
Any Abnormal Crying	55	53
Grade 3 Abnormal Crying (> 3 hours)	3	0
Any Drowsiness	46	47
Grade 3 Drowsiness (Slept most of time)	1	2
Any Loss of Appetite	53	51
Grade 3 Loss of Appetite (Refuses ≥ 3 feeds)	5	2
Any Irritability	74	78
Grade 3 Irritability (Inconsolable)	5	0

Adverse Events

Time Frame	Adverse event data were collected for 2 months post-vaccination.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Fluzone®-Primed Group		Fluzone®-Naive Group
Arm/Group Description	Participants had received two doses of the 2005-2006 formulation of Fluzone® vaccine in the fall of 2005 (Study GRC28 NCT00242424); they received two doses of Fluzone® Pediatric 2006-2007 formulation.		Participants had never received influenza vaccine and had received two doses of placebo (Study GRC28 NCT00242424); they received two doses of Fluzone® Pediatric 2006-2007 formulation.
All-Cause Mortality
	Fluzone®-Primed Group		Fluzone®-Naive Group
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Fluzone®-Primed Group		Fluzone®-Naive Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/116 (0.86%)		0/57 (0.00%)
Infections and infestations
Gastroenteritis * 1	1/116 (0.86%)	1	0/57 (0.00%)	0
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 9.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Fluzone®-Primed Group		Fluzone®-Naive Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	87/116 (75.00%)		40/57 (70.18%)
Gastrointestinal disorders
Diarrhoea * 1	23/116 (19.83%)	27	13/57 (22.81%)	14
Teething * 1	20/116 (17.24%)	30	5/57 (8.77%)	6
Vomiting * 1	17/116 (14.66%)	17	5/57 (8.77%)	5
General disorders
Pyrexia * 1	19/116 (16.38%)	20	11/57 (19.30%)	12
Infections and infestations
Croup infectious * 1	7/116 (6.03%)	7	1/57 (1.75%)	1
Nasopharyngitis * 1	13/116 (11.21%)	15	6/57 (10.53%)	6
Otitis media * 1	26/116 (22.41%)	28	9/57 (15.79%)	10
Upper respiratory tract infection * 1	24/116 (20.69%)	31	9/57 (15.79%)	9
Respiratory, thoracic and mediastinal disorders
Cough * 1	22/116 (18.97%)	25	15/57 (26.32%)	17
Nasal congestion * 1	7/116 (6.03%)	7	5/57 (8.77%)	5
Rhinorrhoea * 1	21/116 (18.10%)	25	6/57 (10.53%)	7
Skin and subcutaneous tissue disorders
Rash * 1	3/116 (2.59%)	3	3/57 (5.26%)	3
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 9.0

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: NCT00390884
• Other Study ID Numbers: GRC29
• First Submitted: October 20, 2006
• First Posted: October 23, 2006
• Results First Submitted: September 21, 2009
• Results First Posted: December 31, 2009
• Last Update Posted: April 14, 2016