Trial Outcomes & Findings for Study of Safety and Immunogenicity of Fluzone® in Healthy Children (NCT NCT00831675)

Last Updated: 2016-04-14

Results Overview

Solicited local reactions: Erythema, bruising, induration, pain at injection site. Solicited systemic reactions: Fever (temperature), irritability, crying, lethargy, appetite decreased, diarrhea, vomiting, rash collected daily for four days after each injection.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

30 participants

Primary outcome timeframe

Days 0-3 Post-dose

Results posted on

2016-04-14

Participant Flow

The study participants took part in the study from 16 September through 18 November 2004 in 1 US site.

A total of 30 participants who met the inclusion and exclusion criteria were enrolled and vaccinated.

Participant milestones

Participant milestones
Measure	Infants <12 Months Participants aged ≥ 6 to \< 12 months at enrollment and received 0.25 mL intramuscular injection of Fluzone® vaccine on Day 0 and on Day 28, respectively.	Toddlers ≥12 Months Participants aged ≥ 12 to \< 36 months at enrollment and received 0.25 mL intramuscular injection of Fluzone® vaccine on Day 0 and on Day 28, respectively.
Overall Study STARTED	12	18
Overall Study COMPLETED	12	18
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of Safety and Immunogenicity of Fluzone® in Healthy Children

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Infants <12 Months n=12 Participants Participants aged ≥ 6 to \< 12 months at enrollment and received 0.25 mL intramuscular injection of Fluzone® vaccine on Day 0 and on Day 28, respectively.	Toddlers ≥12 Months n=18 Participants Participants aged ≥ 12 to \< 36 months at enrollment and received 0.25 mL intramuscular injection of Fluzone® vaccine on Day 0 and on Day 28, respectively.	Total n=30 Participants Total of all reporting groups
Age, Categorical <=18 years	12 Participants n=5 Participants	18 Participants n=7 Participants	30 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	8.9 Months STANDARD_DEVIATION 2.1 • n=5 Participants	20 Months STANDARD_DEVIATION 6.0 • n=7 Participants	15.6 Months STANDARD_DEVIATION 7.3 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	9 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants	18 participants n=7 Participants	30 participants n=5 Participants

PRIMARY outcome

Timeframe: Days 0-3 Post-dose

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

Outcome measures

Outcome measures
Measure	Infants <12 Months n=12 Participants Participants aged ≥ 6 to \< 12 months at enrollment and received 0.25 mL intramuscular injection of Fluzone® vaccine on Day 0 and on Day 28, respectively.	Toddlers ≥12 Months n=18 Participants Participants aged ≥ 12 to \< 36 months at enrollment and received 0.25 mL intramuscular injection of Fluzone® vaccine on Day 0 and on Day 28, respectively.
Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation Any Solicited Local Reaction Post-dose 1	3 Participants	7 Participants
Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation Any Erythema (>0.5 cm)	0 Participants	2 Participants
Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation Grade 3 Erythema (>5.0 cm)	0 Participants	0 Participants
Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation Any Induration (>0.5 cm)	0 Participants	0 Participants
Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation Grade 3 Induration (>5.0 cm)	0 Participants	0 Participants
Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation Any Bruising (>0.5 cm)	2 Participants	0 Participants
Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation Grade 3 Bruising (>5.0 cm)	0 Participants	0 Participants
Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation Any Pain	4 Participants	4 Participants
Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation Grade 3 Pain (Cry When inj. Limb is Moved)	0 Participants	0 Participants
Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation Any Solicited Local Reaction Post-dose 2	4 Participants	4 Participants
Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation Any Erythema (> 0.5 cm)	2 Participants	0 Participants
Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation Grade 3 Pain (Cry When inj. Limb Is Moved)	0 Participants	0 Participants
Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation Any Solicited Systemic Reaction Post-dose 1	7 Participants	12 Participants
Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation Any Fever	1 Participants	3 Participants
Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation Grade 3 Fever (>103.1 ºF)	0 Participants	0 Participants
Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation Any Irritability	5 Participants	6 Participants
Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation Grade 3 Irritability (>3 hours)	1 Participants	0 Participants
Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation Any Crying	4 Participants	3 Participants
Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation Grade 3 Crying (>3 hours)	0 Participants	0 Participants
Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation Any Lethargy	1 Participants	1 Participants
Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation Grade 3 Lethargy (Disabling)	0 Participants	0 Participants
Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation Any Appetite Decreased	3 Participants	6 Participants
Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation Grade 3 Appetite Decreased (refuses over 3 feeds)	0 Participants	0 Participants
Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation Any Vomiting	1 Participants	2 Participants
Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation Grade 3 Vomiting (3 or more episodes)	0 Participants	0 Participants
Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation Any Diarrhea	3 Participants	0 Participants
Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation Grade 3 Diarrhea (>5 Diarrhea Stools)	0 Participants	0 Participants
Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation Rash - Presence of Welts	1 Participants	0 Participants
Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation Any Solicited Systemic Reaction Post-dose 2	6 Participants	10 Participants
Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation Grade 3 Appetite Decreased (refuses 3 feeds)	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 14 days post-vaccination

Population: GMTs were evaluated in the per-protocol population

Outcome measures

Outcome measures
Measure	Infants <12 Months n=12 Participants Participants aged ≥ 6 to \< 12 months at enrollment and received 0.25 mL intramuscular injection of Fluzone® vaccine on Day 0 and on Day 28, respectively.	Toddlers ≥12 Months n=18 Participants Participants aged ≥ 12 to \< 36 months at enrollment and received 0.25 mL intramuscular injection of Fluzone® vaccine on Day 0 and on Day 28, respectively.
Geometric Mean Titers (GMTs) of Hemagglutination Antibodies Pre- and Post-Vaccination With Fluzone® Vaccine 2004-2005 Pediatric Formulation A/New Caledonia/20/99, Pre-dose	7.9 Titers Interval 6.4 to 9.9	9.4 Titers Interval 7.0 to 12.8
Geometric Mean Titers (GMTs) of Hemagglutination Antibodies Pre- and Post-Vaccination With Fluzone® Vaccine 2004-2005 Pediatric Formulation A/New Caledonia/20/99, Post-dose	15.0 Titers Interval 11.2 to 20.1	26.2 Titers Interval 15.8 to 43.3
Geometric Mean Titers (GMTs) of Hemagglutination Antibodies Pre- and Post-Vaccination With Fluzone® Vaccine 2004-2005 Pediatric Formulation A/Wyoming/03/2003, Pre-dose	7.9 Titers Interval 4.8 to 13.2	14.4 Titers Interval 6.5 to 31.8
Geometric Mean Titers (GMTs) of Hemagglutination Antibodies Pre- and Post-Vaccination With Fluzone® Vaccine 2004-2005 Pediatric Formulation A/Wyoming/03/2003, Post-dose	31.7 Titers Interval 12.9 to 78.2	108.9 Titers Interval 44.8 to 264.7
Geometric Mean Titers (GMTs) of Hemagglutination Antibodies Pre- and Post-Vaccination With Fluzone® Vaccine 2004-2005 Pediatric Formulation B/Jiangsu/10/2003, Pre-dose	5.0 Titers Interval 5.0 to 5.0	5.0 Titers Interval 5.0 to 5.0
Geometric Mean Titers (GMTs) of Hemagglutination Antibodies Pre- and Post-Vaccination With Fluzone® Vaccine 2004-2005 Pediatric Formulation B/Jiangsu/10/2003, Post-dose	7.5 Titers Interval 5.0 to 11.1	8.4 Titers Interval 6.5 to 10.8

OTHER_PRE_SPECIFIED outcome

Timeframe: 14 days post-vaccination

Population: Seroprotection were evaluated in the per-protocol population

Seroprotection defined as percentage of participants with reciprocal hemagglutination inhibition titers ≥40 post-vaccination with Fluzone®.

Outcome measures

Outcome measures
Measure	Infants <12 Months n=12 Participants Participants aged ≥ 6 to \< 12 months at enrollment and received 0.25 mL intramuscular injection of Fluzone® vaccine on Day 0 and on Day 28, respectively.	Toddlers ≥12 Months n=18 Participants Participants aged ≥ 12 to \< 36 months at enrollment and received 0.25 mL intramuscular injection of Fluzone® vaccine on Day 0 and on Day 28, respectively.
Percentage of Participants With at Least a 40 Serum Hemagglutination Inhibition Antibody Titers Post-Vaccination (Seroprotection) A/New Caledonia/20/99	8 Percentage of Participants	39 Percentage of Participants
Percentage of Participants With at Least a 40 Serum Hemagglutination Inhibition Antibody Titers Post-Vaccination (Seroprotection) A/Wyoming/03/2003	50 Percentage of Participants	67 Percentage of Participants
Percentage of Participants With at Least a 40 Serum Hemagglutination Inhibition Antibody Titers Post-Vaccination (Seroprotection) B/Jiangsu/10/2003	8 Percentage of Participants	0 Percentage of Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 14 post-vaccination

Population: Seroconversion were evaluated in the per-protocol population.

Seroconversion defined as the percentage of participants with a ≥ 4-fold increases in titer from pre- to post-vaccination with Fluzone®.

Outcome measures

Outcome measures
Measure	Infants <12 Months n=12 Participants Participants aged ≥ 6 to \< 12 months at enrollment and received 0.25 mL intramuscular injection of Fluzone® vaccine on Day 0 and on Day 28, respectively.	Toddlers ≥12 Months n=18 Participants Participants aged ≥ 12 to \< 36 months at enrollment and received 0.25 mL intramuscular injection of Fluzone® vaccine on Day 0 and on Day 28, respectively.
Percentage of Participants With a 4-Fold Increase in Serum Hemagglutination Inhibition Antibody Titers Post-Vaccination (Seroconversion) A/New Caledonia/20/99	33 Percentage of Participants	50 Percentage of Participants
Percentage of Participants With a 4-Fold Increase in Serum Hemagglutination Inhibition Antibody Titers Post-Vaccination (Seroconversion) A/Wyoming/03/2003	58 Percentage of Participants	100 Percentage of Participants
Percentage of Participants With a 4-Fold Increase in Serum Hemagglutination Inhibition Antibody Titers Post-Vaccination (Seroconversion) B/Jiangsu/10/2003	8 Percentage of Participants	17 Percentage of Participants

Adverse Events

Infants <12 Months

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Toddlers ≥12 Months

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

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
Publication restrictions are in place

Restriction type: OTHER

Measure	Infants <12 Months n=12 participants at risk Participants aged ≥ 6 to \< 12 months at enrollment and received 0.25 mL intramuscular injection of Fluzone® vaccine on Day 0 and on Day 28, respectively.	Toddlers ≥12 Months n=18 participants at risk Participants aged ≥ 12 to \< 36 months at enrollment and received 0.25 mL intramuscular injection of Fluzone® vaccine on Day 0 and on Day 28, respectively.
Eye disorders Conjunctivitis	0.00% 0/12 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	5.6% 1/18 • Number of events 1 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.
Gastrointestinal disorders Diarrhoea NOS	16.7% 2/12 • Number of events 2 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	0.00% 0/18 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.
Gastrointestinal disorders Gingival swelling	0.00% 0/12 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	5.6% 1/18 • Number of events 1 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.
Gastrointestinal disorders Teething	58.3% 7/12 • Number of events 9 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	16.7% 3/18 • Number of events 3 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.
Gastrointestinal disorders Vomiting NOS	8.3% 1/12 • Number of events 1 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	0.00% 0/18 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.
General disorders Pyrexia	33.3% 4/12 • Number of events 4 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	22.2% 4/18 • Number of events 4 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.
Infections and infestations Bronchiolitis	0.00% 0/12 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	5.6% 1/18 • Number of events 1 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.
Infections and infestations Coxsackie viral infection	0.00% 0/12 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	5.6% 1/18 • Number of events 1 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.
Infections and infestations Gastroenteritis NOS	8.3% 1/12 • Number of events 1 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	0.00% 0/18 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.
Infections and infestations Hand-foot-and-mouth disease	0.00% 0/12 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	5.6% 1/18 • Number of events 1 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.
Infections and infestations Nasopharyngitis	8.3% 1/12 • Number of events 1 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	16.7% 3/18 • Number of events 3 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.
Infections and infestations Oral candidiasis	8.3% 1/12 • Number of events 1 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	0.00% 0/18 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.
Infections and infestations Otitis media NOS	25.0% 3/12 • Number of events 3 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	16.7% 3/18 • Number of events 3 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.
Infections and infestations Pharyngitis	0.00% 0/12 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	5.6% 1/18 • Number of events 1 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.
Infections and infestations Pharyngitis streptococcal	0.00% 0/12 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	5.6% 1/18 • Number of events 1 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.
Infections and infestations Pneumonia NOS	0.00% 0/12 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	5.6% 1/18 • Number of events 1 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.
Infections and infestations Rhinitis infective	8.3% 1/12 • Number of events 1 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	0.00% 0/18 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.
Infections and infestations Sinusitis NOS	16.7% 2/12 • Number of events 2 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	5.6% 1/18 • Number of events 1 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.
Infections and infestations Upper respiratory tract infection NOS	41.7% 5/12 • Number of events 5 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	11.1% 2/18 • Number of events 2 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.
Infections and infestations Upper respiratory tract infection viral NOS	0.00% 0/12 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	5.6% 1/18 • Number of events 1 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/12 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	5.6% 1/18 • Number of events 1 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.
Injury, poisoning and procedural complications Thermal burn	0.00% 0/12 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	5.6% 1/18 • Number of events 1 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.
Investigations Body temperature increased	8.3% 1/12 • Number of events 1 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	0.00% 0/18 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.
Psychiatric disorders Irritability	0.00% 0/12 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	5.6% 1/18 • Number of events 1 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.
Respiratory, thoracic and mediastinal disorders Asthma NOS	0.00% 0/12 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	5.6% 1/18 • Number of events 1 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.
Respiratory, thoracic and mediastinal disorders Cough	33.3% 4/12 • Number of events 4 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	16.7% 3/18 • Number of events 4 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.
Respiratory, thoracic and mediastinal disorders Nasal congestion	8.3% 1/12 • Number of events 1 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	0.00% 0/18 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	25.0% 3/12 • Number of events 3 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	11.1% 2/18 • Number of events 4 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.
Respiratory, thoracic and mediastinal disorders Dermatitis NOS	0.00% 0/12 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	5.6% 1/18 • Number of events 1 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.
Skin and subcutaneous tissue disorders Rash NOS	8.3% 1/12 • Number of events 1 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	0.00% 0/18 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.
Skin and subcutaneous tissue disorders Urticaria NOS	0.00% 0/12 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.	5.6% 1/18 • Number of events 1 • Adverse event data were collected from the day of vaccination to Day 42 post-vaccination.