Trial Outcomes & Findings for Phase IV Trial to Collect Safety Data and Sera for Immunogenicity Testing in Healthy Children Given Fluzone® Vaccine (NCT NCT00561002)

Last Updated: 2016-04-14

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

34 participants

Primary outcome timeframe

Days 0-3 post-dose

Results posted on

2016-04-14

Participant Flow

The study participants were enrolled from 29 October 2007 through 27 November 2007 at 1 US site.

A total of 34 participants who met the inclusion and exclusion criteria were enrolled, 2 were not vaccinated and excluded from the analysis.

Participant milestones

Participant milestones
Measure	Influenza Vaccine Naive/Inadequately Primed Participants had no more than one previous lifetime dose of influenza vaccine and received two doses of Fluzone®, on Days 0 and 14.	Influenza Vaccine Primed Participants had previously received 2 injections of Influenza vaccine in the same season and received a single dose of Fluzone® on Day 0.
Overall Study STARTED	23	9
Overall Study COMPLETED	23	9
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Influenza Vaccine Naive/Inadequately Primed n=23 Participants Participants had no more than one previous lifetime dose of influenza vaccine and received two doses of Fluzone®, on Days 0 and 14.	Influenza Vaccine Primed n=9 Participants Participants had previously received 2 injections of Influenza vaccine in the same season and received a single dose of Fluzone® on Day 0.	Total n=32 Participants Total of all reporting groups
Age, Categorical <=18 years	23 Participants n=5 Participants	9 Participants n=7 Participants	32 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous Age Continuous	19.8 Months STANDARD_DEVIATION 8.76 • n=5 Participants	24.5 Months STANDARD_DEVIATION 5.10 • n=7 Participants	21.2 Months STANDARD_DEVIATION 8.11 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	4 Participants n=7 Participants	17 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	5 Participants n=7 Participants	15 Participants n=5 Participants
Region of Enrollment United States	23 participants n=5 Participants	9 participants n=7 Participants	32 participants n=5 Participants

PRIMARY outcome

Timeframe: Days 0-3 post-dose

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

Outcome measures

Outcome measures
Measure	Influenza Vaccine Naive/Inadequately Primed n=23 Participants Participants had no more than one previous lifetime dose of influenza vaccine and received two doses of Fluzone®, on Days 0 and 14.	Influenza Vaccine Primed n=9 Participants Participants had previously received 2 injections of Influenza vaccine in the same season and received a single dose of Fluzone® on Day 0.
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Any Fever	6 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Grade 3 Abnormal Crying (> 3 hr)	0 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Grade 3 Myalgia (Prevents activities)	0 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Any Solicited Injection Site Reaction Post-dose 1	13 Participants	4 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Any Tenderness	10 Participants	2 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Grd 3 Tenderness (Cries when limb is moved)	1 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Any Pain	3 Participants	2 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Grd 3 Pain (Incapacitating)	0 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Any Redness (> 0.5 cm)	3 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Grade 3 Redness (≥ 5.0 cm)	0 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Any Swelling (> 0.5 cm)	2 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Grade 3 Swelling (≥ 5.0 cm)	0 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Any Solicited Injection Site Reaction Post-dose 2	7 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Grade 3 Redness) (≥ 5.0 cm)	0 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Any Solicited Injection Reaction - Any dose	14 Participants	4 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Grade 3 Tenderness (Cries when limb moved)	1 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Grade 3 Pain (Incapacitating)	0 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Grade 3 Irritability (Inconsolable)	1 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Any Solicited Systemic Reaction Post-dose 1	14 Participants	6 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Grade 3 Fever (>103.1 ºF)	1 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Any Vomiting	1 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Grade 3 Vomiting (≥ episodes per 24 hr)	0 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Any Abnormal Crying	10 Participants	2 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Any Drowsiness	8 Participants	3 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Grade 3 Drowsiness (Sleeps most of the time)	0 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Any Loss of Appetite	9 Participants	1 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Grade 3 Loss of Appetite (Refuses most feeds)	0 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Any Irritability	12 Participants	3 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Any Headache	0 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Grade 3 Headache (Prevents daily activities)	0 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Any Myalgia	1 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Grade 3 Myalgia (Prevents daily activities)	0 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Any Malaise	3 Participants	3 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Grade 3 Malaise (Prevents daily activities)	0 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Any Solicited Systemic Reaction Post-dose 2	11 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Grade 3 Fever (> 103ºF)	0 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Grade 3 Vomiting (≥ 6 episodes per 24 hr)	0 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Grade 3 Abnormal Crying (>3 hr)	0 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Grade 3 Drowsiness (Sleeps most of time)	0 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Any Solicited Systemic Reaction (Any dose)	16 Participants	6 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Grade 3 Fever (> 103.1 ºF)	1 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Grade 3 Headache (Prevents activities)	0 Participants	0 Participants
Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation Grade 3 Malaise (Prevents activities)	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 0 and Day 14 after last dose of Fluzone

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

Outcome measures

Outcome measures
Measure	Influenza Vaccine Naive/Inadequately Primed n=16 Participants Participants had no more than one previous lifetime dose of influenza vaccine and received two doses of Fluzone®, on Days 0 and 14.	Influenza Vaccine Primed n=6 Participants Participants had previously received 2 injections of Influenza vaccine in the same season and received a single dose of Fluzone® on Day 0.
Geometric Mean Titers (GMTs) of Hemagglutinin Antibodies Pre- and Post-Fluzone® Vaccination A/Solomon Islands/3/2006 IVR-145 (H1N1) Pre-dose	8.31 Titers Interval 4.48 to 15.4	5.61 Titers Interval 4.17 to 7.55
Geometric Mean Titers (GMTs) of Hemagglutinin Antibodies Pre- and Post-Fluzone® Vaccination A/Wisconsin/67/2005 (X-161B) (H3N2) Pre-dose	10.7 Titers Interval 5.11 to 22.5	59.9 Titers Interval 8.94 to 402.0
Geometric Mean Titers (GMTs) of Hemagglutinin Antibodies Pre- and Post-Fluzone® Vaccination Wisconsin/67/2005 (X161B) (H3N2) Post-dose	260 Titers Interval 168.0 to 401.0	479 Titers Interval 200.0 to 1148.0
Geometric Mean Titers (GMTs) of Hemagglutinin Antibodies Pre- and Post-Fluzone® Vaccination A/Solomon Islands/3/2006 IVR-145 (H1N1) Post-dose	397 Titers Interval 243.0 to 649.0	180 Titers Interval 63.1 to 511.0
Geometric Mean Titers (GMTs) of Hemagglutinin Antibodies Pre- and Post-Fluzone® Vaccination B/Malaysia Split/2506/2004 Pre-dose	12.3 Titers Interval 5.96 to 25.4	13.3 Titers Interval 3.92 to 45.5
Geometric Mean Titers (GMTs) of Hemagglutinin Antibodies Pre- and Post-Fluzone® Vaccination B/Malaysia Split/2506/2004 Post-dose	186 Titers Interval 72.6 to 477.0	180 Titers Interval 70.2 to 459.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 14 post-vaccination

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

Seroprotection was defined as a serum hemagglutination inhibition antibody titer ≥40.

Outcome measures

Outcome measures
Measure	Influenza Vaccine Naive/Inadequately Primed n=16 Participants Participants had no more than one previous lifetime dose of influenza vaccine and received two doses of Fluzone®, on Days 0 and 14.	Influenza Vaccine Primed n=6 Participants Participants had previously received 2 injections of Influenza vaccine in the same season and received a single dose of Fluzone® on Day 0.
Percentage of Participants With at Least a 40 Serum Hemagglutination Inhibition Antibody Titers Post-Vaccination (Seroprotection) A/Solomon Islands/3/2006 IVR-145 (H1N1)	100 Percentage of Participants	83 Percentage of Participants
Percentage of Participants With at Least a 40 Serum Hemagglutination Inhibition Antibody Titers Post-Vaccination (Seroprotection) A/Wisconsin/67/2005 (X-161B) (H3N2)	100 Percentage of Participants	100 Percentage of Participants
Percentage of Participants With at Least a 40 Serum Hemagglutination Inhibition Antibody Titers Post-Vaccination (Seroprotection) B/Malaysia Split/2506/2004	81 Percentage of Participants	100 Percentage of Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 14 post-vaccination

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

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.

Outcome measures

Outcome measures
Measure	Influenza Vaccine Naive/Inadequately Primed n=16 Participants Participants had no more than one previous lifetime dose of influenza vaccine and received two doses of Fluzone®, on Days 0 and 14.	Influenza Vaccine Primed n=6 Participants Participants had previously received 2 injections of Influenza vaccine in the same season and received a single dose of Fluzone® on Day 0.
Seroconversion Rates for Each Influenza Antigen Post-Vaccination A/Solomon Islands/3/2006 IVR-145 (H1N1)	100 Percentage of Participants	83 Percentage of Participants
Seroconversion Rates for Each Influenza Antigen Post-Vaccination A/Wisconsin/67/2005 (X-161B) (H3N2)	79 Percentage of Participants	67 Percentage of Participants
Seroconversion Rates for Each Influenza Antigen Post-Vaccination B/Malaysia Split/2506/2004	80 Percentage of Participants	100 Percentage of Participants

Adverse Events

Influenza Vaccine Naive/Inadequately Primed

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Influenza Vaccine Primed

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Influenza Vaccine Naive/Inadequately Primed n=23 participants at risk Participants had no more than one previous lifetime dose of influenza vaccine and received two doses of Fluzone®, on Days 0 and 14.	Influenza Vaccine Primed n=9 participants at risk Participants had previously received 2 injections of Influenza vaccine in the same season and received a single dose of Fluzone® on Day 0.
General disorders Injection site tenderness	43.5% 10/23 • 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)	22.2% 2/9 • 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)
General disorders Injection site pain	13.0% 3/23 • 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)	22.2% 2/9 • 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)
General disorders Injection site redness	13.0% 3/23 • 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)	0.00% 0/9 • 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)
General disorders Injection site swelling	8.7% 2/23 • 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)	0.00% 0/9 • 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)
General disorders Pyrexia	26.1% 6/23 • 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)	22.2% 2/9 • 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)
Psychiatric disorders Crying	43.5% 10/23 • 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)	22.2% 2/9 • 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)
Nervous system disorders Somnolence	34.8% 8/23 • 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)	33.3% 3/9 • 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)
Metabolism and nutrition disorders Anorexia	39.1% 9/23 • 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)	11.1% 1/9 • 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)
Psychiatric disorders Irritability	52.2% 12/23 • 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)	33.3% 3/9 • 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)
General disorders Malaise	13.0% 3/23 • 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)	33.3% 3/9 • 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)

Additional Information

Medical Director

Sanofi Pasteur Inc.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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
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