Phase IV Trial to Collect Safety Data and Sera for Immunogenicity Testing in Healthy Children Given Fluzone® Vaccine

• ClinicalTrials.gov Identifier: NCT00561002
• Recruitment Status: Completed
• First Posted: November 20, 2007
• Results First Posted: August 27, 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: 2007-2008 Influenza Virus Vaccine
• Enrollment: 34

Participant Flow

Recruitment Details	The study participants were enrolled from 29 October 2007 through 27 November 2007 at 1 US site.
Pre-assignment Details	A total of 34 participants who met the inclusion and exclusion criteria were enrolled, 2 were not vaccinated and excluded from the analysis.

Arm/Group Title	Influenza Vaccine Naive/Inadequately Primed	Influenza Vaccine Primed
Arm/Group Description	Participants had no more than one previous lifetime dose of influenza vaccine and received two doses of Fluzone®, on Days 0 and 14.	Participants had previously received 2 injections of Influenza vaccine in the same season and received a single dose of Fluzone® on Day 0.
Period Title: Overall Study
Started	23	9
Completed	23	9
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		Influenza Vaccine Naive/Inadequately Primed	Influenza Vaccine Primed	Total
Arm/Group Description		Participants had no more than one previous lifetime dose of influenza vaccine and received two doses of Fluzone®, on Days 0 and 14.	Participants had previously received 2 injections of Influenza vaccine in the same season and received a single dose of Fluzone® on Day 0.	Total of all reporting groups
Overall Number of Baseline Participants		23	9	32
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	23 participants	9 participants	32 participants
	<=18 years	23 100.0%	9 100.0%	32 100.0%
	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
Age Continuous	Number Analyzed	23 participants	9 participants	32 participants
		19.8 (8.76)	24.5 (5.10)	21.2 (8.11)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	23 participants	9 participants	32 participants
	Female	13 56.5%	4 44.4%	17 53.1%
	Male	10 43.5%	5 55.6%	15 46.9%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	23 participants	9 participants	32 participants
		23	9	32

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation
Description	Solicited injection site reactions: Erythema, swelling, pain/tenderness; Solicited systemic reactions: (for infants/toddlers) - fever, irritability, abnormal crying, drowsiness, lost appetite, vomiting; (for children) - fever, headache, malaise, myalgia) Note: Influenza-primed group received only dose 1.
Time Frame	Days 0-3 post-dose

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	Influenza Vaccine Naive/Inadequately Primed	Influenza Vaccine Primed
Arm/Group Description:	Participants had no more than one previous lifetime dose of influenza vaccine and received two doses of Fluzone®, on Days 0 and 14.	Participants had previously received 2 injections of Influenza vaccine in the same season and received a single dose of Fluzone® on Day 0.
Overall Number of Participants Analyzed	23	9
Measure Type: Number; Unit of Measure: Participants
Any Solicited Injection Site Reaction Post-dose 1	13	4
Any Tenderness	9	2
Grd 3 Tenderness (Cries when limb is moved)	0	0
Any Pain	3	2
Grd 3 Pain (Incapacitating)	0	0
Any Redness (> 0.5 cm)	3	0
Grade 3 Redness (≥ 5.0 cm)	0	0
Any Swelling (> 0.5 cm)	2	0
Grade 3 Swelling (≥ 5.0 cm)	0	0
Any Solicited Injection Site Reaction Post-dose 2	7	0
Any Tenderness	6	0
Grd 3 Tenderness (Cries when limb is moved)	1	0
Any Pain	1	0
Grd 3 Pain (Incapacitating)	0	0
Any Redness (> 0.5 cm)	0	0
Grade 3 Redness) (≥ 5.0 cm)	0	0
Any Swelling (> 0.5 cm)	0	0
Grade 3 Swelling (≥ 5.0 cm)	0	0
Any Solicited Injection Reaction - Any dose	14	4
Any Tenderness	10	2
Grade 3 Tenderness (Cries when limb moved)	1	0
Any Pain	3	2
Grade 3 Pain (Incapacitating)	0	0
Any Redness (> 0.5 cm)	3	0
Grade 3 Redness (≥ 5.0 cm)	0	0
Any Swelling (> 0.5 cm)	2	0
Grade 3 Swelling (≥ 5.0 cm)	0	0
Any Solicited Systemic Reaction Post-dose 1	14	6
Any Fever	4	2
Grade 3 Fever (>103.1 ºF)	1	0
Any Vomiting	1	0
Grade 3 Vomiting (≥ episodes per 24 hr)	0	0
Any Abnormal Crying	9	2
Grade 3 Abnormal Crying (> 3 hr)	0	0
Any Drowsiness	7	3
Grade 3 Drowsiness (Sleeps most of the time)	0	0
Any Loss of Appetite	7	1
Grade 3 Loss of Appetite (Refuses most feeds)	0	0
Any Irritability	11	3
Grade 3 Irritability (Inconsolable)	1	0
Any Headache	0	0
Grade 3 Headache (Prevents daily activities)	0	0
Any Myalgia	2	0
Grade 3 Myalgia (Prevents daily activities)	0	0
Any Malaise	3	3
Grade 3 Malaise (Prevents daily activities)	0	0
Any Solicited Systemic Reaction Post-dose 2	11	0
Any Fever	3	0
Grade 3 Fever (> 103ºF)	0	0
Any Vomiting	0	0
Grade 3 Vomiting (≥ 6 episodes per 24 hr)	0	0
Any Abnormal Crying	5	0
Grade 3 Abnormal Crying (>3 hr)	0	0
Any Drowsiness	5	0
Grade 3 Drowsiness (Sleeps most of time)	0	0
Any Loss of Appetite	3	0
Grade 3 Loss of Appetite (Refuses most feeds)	0	0
Any Irritability	7	0
Grade 3 Irritability (Inconsolable)	0	0
Any Headache	0	0
Grade 3 Headache (Prevents daily activities)	0	0
Any Myalgia	1	0
Grade 3 Myalgia (Prevents daily activities)	0	0
Any Malaise	1	0
Grade 3 Malaise (Prevents daily activities)	0	0
Any Solicited Systemic Reaction (Any dose)	16	6
Any Fever	6	2
Grade 3 Fever (> 103.1 ºF)	1	0
Any Vomiting	1	0
Grade 3 Vomiting (≥ 6 episodes per 24 hr)	0	0
Any Abnormal Crying	10	2
Grade 3 Abnormal Crying (> 3 hr)	0	0
Any Drowsiness	8	3
Grade 3 Drowsiness (Sleeps most of the time)	0	0
Any Loss of Appetite	9	1
Grade 3 Loss of Appetite (Refuses most feeds)	0	0
Any Irritability	12	3
Grade 3 Irritability (Inconsolable)	1	0
Any Headache	0	0
Grade 3 Headache (Prevents activities)	0	0
Any Myalgia	2	0
Grade 3 Myalgia (Prevents activities)	0	0
Any Malaise	3	3
Grade 3 Malaise (Prevents activities)	0	0

2. Other Pre-specified Outcome

Title	Geometric Mean Titers (GMTs) of Hemagglutinin Antibodies Pre- and Post-Fluzone® Vaccination
Description	[Not Specified]
Time Frame	Day 0 and Day 14 after last dose of Fluzone

Outcome Measure Data

Analysis Population Description

The Geometric Mean Titers analysis were on the per-protocol immunogenicity population.

Arm/Group Title	Influenza Vaccine Naive/Inadequately Primed	Influenza Vaccine Primed
Arm/Group Description:	Participants had no more than one previous lifetime dose of influenza vaccine and received two doses of Fluzone®, on Days 0 and 14.	Participants had previously received 2 injections of Influenza vaccine in the same season and received a single dose of Fluzone® on Day 0.
Overall Number of Participants Analyzed	16	6
Geometric Mean (95% Confidence Interval); Unit of Measure: Titers
A/Solomon Islands/3/2006 IVR-145 (H1N1) Pre-dose	8.31; (4.48 to 15.4)	5.61; (4.17 to 7.55)
A/Solomon Islands/3/2006 IVR-145 (H1N1) Post-dose	397; (243 to 649)	180; (63.1 to 511)
A/Wisconsin/67/2005 (X-161B) (H3N2) Pre-dose	10.7; (5.11 to 22.5)	59.9; (8.94 to 402)
Wisconsin/67/2005 (X161B) (H3N2) Post-dose	260; (168 to 401)	479; (200 to 1148)
B/Malaysia Split/2506/2004 Pre-dose	12.3; (5.96 to 25.4)	13.3; (3.92 to 45.5)
B/Malaysia Split/2506/2004 Post-dose	186; (72.6 to 477)	180; (70.2 to 459)

3. Other Pre-specified Outcome

Title	Percentage of Participants With at Least a 40 Serum Hemagglutination Inhibition Antibody Titers Post-Vaccination (Seroprotection)
Description	Seroprotection was defined as a serum hemagglutination inhibition antibody titer ≥40.
Time Frame	Day 14 post-vaccination

Outcome Measure Data

Analysis Population Description

The serum hemagglutination inhibition antibody analysis were on the per-protocol immunogenicity population.

Arm/Group Title	Influenza Vaccine Naive/Inadequately Primed	Influenza Vaccine Primed
Arm/Group Description:	Participants had no more than one previous lifetime dose of influenza vaccine and received two doses of Fluzone®, on Days 0 and 14.	Participants had previously received 2 injections of Influenza vaccine in the same season and received a single dose of Fluzone® on Day 0.
Overall Number of Participants Analyzed	16	6
Measure Type: Number; Unit of Measure: Percentage of Participants
A/Solomon Islands/3/2006 IVR-145 (H1N1)	100	83
A/Wisconsin/67/2005 (X-161B) (H3N2)	100	100
B/Malaysia Split/2506/2004	81	100

4. Other Pre-specified Outcome

Title	Seroconversion Rates for Each Influenza Antigen Post-Vaccination
Description	Seroconversion was defined as a post-vaccination titer ≥ 40 for participants with a titer < 10 on Day 0 and a ≥4-fold increase for participants with a titer ≥ 10 on Day 0.
Time Frame	Day 14 post-vaccination

Outcome Measure Data

Analysis Population Description

The seroconversion analysis were on the per-protocol immunogenicity population.

Arm/Group Title	Influenza Vaccine Naive/Inadequately Primed	Influenza Vaccine Primed
Arm/Group Description:	Participants had no more than one previous lifetime dose of influenza vaccine and received two doses of Fluzone®, on Days 0 and 14.	Participants had previously received 2 injections of Influenza vaccine in the same season and received a single dose of Fluzone® on Day 0.
Overall Number of Participants Analyzed	16	6
Measure Type: Number; Unit of Measure: Percentage of Participants
A/Solomon Islands/3/2006 IVR-145 (H1N1)	100	83
A/Wisconsin/67/2005 (X-161B) (H3N2)	79	67
B/Malaysia Split/2506/2004	80	100

Adverse Events

Time Frame	Adverse events data were collected from the day of vaccination for 14 days post-vaccination (Influenza Vaccine Primed group) or 42 days post-vaccination (Influenza Vaccine Naïve/Inadequately Primed group)
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Influenza Vaccine Naive/Inadequately Primed	Influenza Vaccine Primed
Arm/Group Description	Participants had no more than one previous lifetime dose of influenza vaccine and received two doses of Fluzone®, on Days 0 and 14.	Participants had previously received 2 injections of Influenza vaccine in the same season and received a single dose of Fluzone® on Day 0.
All-Cause Mortality
	Influenza Vaccine Naive/Inadequately Primed	Influenza Vaccine Primed
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Influenza Vaccine Naive/Inadequately Primed	Influenza Vaccine Primed
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/23 (0.00%)	0/9 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Influenza Vaccine Naive/Inadequately Primed	Influenza Vaccine Primed
	Affected / at Risk (%)	Affected / at Risk (%)
Total	12/23 (52.17%)	3/9 (33.33%)
General disorders
Injection site tenderness † 1	10/23 (43.48%)	2/9 (22.22%)
Injection site pain † 1	3/23 (13.04%)	2/9 (22.22%)
Injection site redness † 1	3/23 (13.04%)	0/9 (0.00%)
Injection site swelling † 1	2/23 (8.70%)	0/9 (0.00%)
Pyrexia † 1	6/23 (26.09%)	2/9 (22.22%)
Malaise † 1	3/23 (13.04%)	3/9 (33.33%)
Metabolism and nutrition disorders
Anorexia † 1	9/23 (39.13%)	1/9 (11.11%)
Nervous system disorders
Somnolence † 1	8/23 (34.78%)	3/9 (33.33%)
Psychiatric disorders
Crying † 1	10/23 (43.48%)	2/9 (22.22%)
Irritability † 1	12/23 (52.17%)	3/9 (33.33%)
† Indicates events were collected by 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: NCT00561002
• Other Study ID Numbers: GRC38
• First Submitted: November 19, 2007
• First Posted: November 20, 2007
• Results First Submitted: July 20, 2009
• Results First Posted: August 27, 2009
• Last Update Posted: April 14, 2016