Trial Outcomes & Findings for Safety and Immunogenicity Testing of Influenza Vaccine in Healthy Children 2 Months and 6 Months of Age (NCT NCT00858468)

Last Updated: 2016-04-14

Results Overview

Solicited local (injection site) reactions: Tenderness, erythema (redness), and swelling Solicited systemic reactions: Fever (Temperature), Vomiting, Crying abnormal, Drowsiness, Loss of Appetite, and Irritability.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

394 participants

Primary outcome timeframe

Day 0 to Day 7 post-vaccination

Results posted on

2016-04-14

Participant Flow

Participants were enrolled from 08 April to 05 August 2005 in 8 medical centers in the US

A total of 394 participants that met the inclusion and exclusion criteria were enrolled, 393 were vaccinated.

Participant milestones

Participant milestones
Measure	Age 6 to 12 Weeks Participants enrolled at 6 to 12 weeks of age	Age 24 to 36 Weeks Participants enrolled at 24 to 36 weeks of age
Overall Study STARTED	201	192
Overall Study COMPLETED	201	192
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Age 6 to 12 Weeks n=201 Participants Participants enrolled at 6 to 12 weeks of age	Age 24 to 36 Weeks n=192 Participants Participants enrolled at 24 to 36 weeks of age	Total n=393 Participants Total of all reporting groups
Age, Categorical <=18 years	201 Participants n=5 Participants	192 Participants n=7 Participants	393 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	9.4 Weeks STANDARD_DEVIATION 0.98 • n=5 Participants	27.0 Weeks STANDARD_DEVIATION 1.31 • n=7 Participants	18.0 Weeks STANDARD_DEVIATION 8.9 • n=5 Participants
Sex: Female, Male Female	98 Participants n=5 Participants	99 Participants n=7 Participants	197 Participants n=5 Participants
Sex: Female, Male Male	103 Participants n=5 Participants	93 Participants n=7 Participants	196 Participants n=5 Participants
Region of Enrollment United States	201 participants n=5 Participants	192 participants n=7 Participants	393 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 0 to Day 7 post-vaccination

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

Outcome measures

Outcome measures
Measure	Age 6 to 12 Weeks n=201 Participants Participants enrolled at 6 to 12 weeks of age	Age 24 to 36 Weeks n=192 Participants Participants enrolled at 24 to 36 weeks of age
Percentage of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation. Grade 3 Vomiting (≥ 6 episodes per 24 hrs)	2 Percentage of participants	0 Percentage of participants
Percentage of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation. Grade 3 Redness (≥ 5.0 cm)	1 Percentage of participants	0 Percentage of participants
Percentage of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation. Any Redness	16 Percentage of participants	10 Percentage of participants
Percentage of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation. Any Tenderness	57 Percentage of participants	26 Percentage of participants
Percentage of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation. Any Swelling	12 Percentage of participants	2 Percentage of participants
Percentage of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation. Any Solicited Systemic Reaction Dose 1	90 Percentage of participants	82 Percentage of participants
Percentage of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation. Any Fever (Rectal Temp)	11 Percentage of participants	14 Percentage of participants
Percentage of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation. Grade 3 Fever (>39.5 ºC)	0 Percentage of participants	0 Percentage of participants
Percentage of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation. Any Irritability	82 Percentage of participants	76 Percentage of participants
Percentage of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation. Grade 3 Irritability (inconsolable)	3 Percentage of participants	4 Percentage of participants
Percentage of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation. Grade 3 Abnormal Crying	6 Percentage of participants	3 Percentage of participants
Percentage of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation. Any Drowsiness	47 Percentage of participants	38 Percentage of participants
Percentage of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation. Any Loss of Appetite	28 Percentage of participants	47 Percentage of participants
Percentage of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation. Any Abnormal Crying	66 Percentage of participants	55 Percentage of participants
Percentage of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation. Grade 3 Drowsiness (difficulty waking up)	4 Percentage of participants	1 Percentage of participants
Percentage of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation. Grd 3 Loss of Appetite (refuses ≥ 3 meals)	0 Percentage of participants	2 Percentage of participants
Percentage of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation. Any Solicited Systemic Reaction Dose 2	70 Percentage of participants	70 Percentage of participants
Percentage of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation. Any Vomiting	22 Percentage of participants	16 Percentage of participants
Percentage of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation. Grade 3 Loss of Appetite (refuses ≥ 3 meals)	1 Percentage of participants	2 Percentage of participants
Percentage of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation. Any Solicited Systemic Reaction Any Dose	92 Percentage of participants	89 Percentage of participants
Percentage of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation. Any Solicited Injection Site Reaction - Dose 1	54 Percentage of participants	47 Percentage of participants
Percentage of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation. Grd 3 Tenderness-Inj. Limb movement reduced	7 Percentage of participants	2 Percentage of participants
Percentage of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation. Grade 3 Swelling (≥ 5.0 cm)	0 Percentage of participants	0 Percentage of participants
Percentage of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation. Any Solicited Injection Site Reaction - Dose 2	41 Percentage of participants	27 Percentage of participants
Percentage of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation. Grade 3 Swelling (≥5.0 cm)	0 Percentage of participants	0 Percentage of participants
Percentage of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation. Any Solicited Injection Site Reaction - Any Doses	61 Percentage of participants	52 Percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 21 days post-vaccination 2

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

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

Outcome measures

Outcome measures
Measure	Age 6 to 12 Weeks n=149 Participants Participants enrolled at 6 to 12 weeks of age	Age 24 to 36 Weeks n=144 Participants Participants enrolled at 24 to 36 weeks of age
Percentage of Participants With Serum Hemagglutination Inhibition Antibody Titer ≥ 40 Post-vaccination With Fluzone® (Seroprotection). A/NEW CALEDONIA/20/99 ≥ 40 Post-dose	46 Percentage of participants	69 Percentage of participants
Percentage of Participants With Serum Hemagglutination Inhibition Antibody Titer ≥ 40 Post-vaccination With Fluzone® (Seroprotection). A/WYOMING/03/2003 ≥ 40 Post-dose	59 Percentage of participants	78 Percentage of participants
Percentage of Participants With Serum Hemagglutination Inhibition Antibody Titer ≥ 40 Post-vaccination With Fluzone® (Seroprotection). B/JIANGSU/10/2003 ≥ 40 Post-dose	5 Percentage of participants	22 Percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 21 days post-vaccination 2

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

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.

Outcome measures

Outcome measures
Measure	Age 6 to 12 Weeks n=149 Participants Participants enrolled at 6 to 12 weeks of age	Age 24 to 36 Weeks n=144 Participants Participants enrolled at 24 to 36 weeks of age
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). A/NEW CALEDONIA/20/99, Pre-Dose ≤ 10	70 Percentage of participants	96 Percentage of participants
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). A/WYOMING/03/2003, Pre-Dose ≤10, Post-Dose ≥40	60 Percentage of participants	86 Percentage of participants
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). A/NEW CALEDONIA/20/99, Pre-Dose ≤10, Post-Dose ≥40	48 Percentage of participants	72 Percentage of participants
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). A/WYOMING/03/2003, Pre-Dose ≤ 10	32 Percentage of participants	74 Percentage of participants
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). FLU B/JIANGSU/10/2003, Pre-Dose ≤ 10	84 Percentage of participants	97 Percentage of participants
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). FLU B/JIANGSU/10/2003, Pre-Dose ≤10, Post-Dose ≥40	4 Percentage of participants	20 Percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 21 days post-vaccination 2

Population: GMTs were assessed on the Per-Protocol Population

Data presented for each of the three influenza vaccine virus antigens in the Fluzone® 2004-2005 pediatric formulation.

Outcome measures

Outcome measures
Measure	Age 6 to 12 Weeks n=149 Participants Participants enrolled at 6 to 12 weeks of age	Age 24 to 36 Weeks n=144 Participants Participants enrolled at 24 to 36 weeks of age
Geometric Mean Titers (GMTs) of Hemagglutination Antibodies Pre- and Post-vaccination With Fluzone® Vaccine. A/WYOMING/03/2003 Pre-dose	40.8 Titers Interval 31.2 to 53.2	9.8 Titers Interval 8.1 to 11.9
Geometric Mean Titers (GMTs) of Hemagglutination Antibodies Pre- and Post-vaccination With Fluzone® Vaccine. A/NEW CALEDONIA/20/99 Pre-dose	11.5 Titers Interval 9.4 to 14.1	5.7 Titers Interval 5.3 to 6.0
Geometric Mean Titers (GMTs) of Hemagglutination Antibodies Pre- and Post-vaccination With Fluzone® Vaccine. A/NEW CALEDONIA/20/99 Post-dose	27.6 Titers Interval 23.1 to 33.1	47.0 Titers Interval 39.3 to 56.2
Geometric Mean Titers (GMTs) of Hemagglutination Antibodies Pre- and Post-vaccination With Fluzone® Vaccine. A/WYOMING/03/2003 Post-dose	46.3 Titers Interval 38.7 to 55.4	90.9 Titers Interval 72.2 to 114.4
Geometric Mean Titers (GMTs) of Hemagglutination Antibodies Pre- and Post-vaccination With Fluzone® Vaccine. B/JIANGSU/10/2003 Pre-dose	7.0 Titers Interval 6.3 to 7.8	5.4 Titers Interval 5.1 to 5.7
Geometric Mean Titers (GMTs) of Hemagglutination Antibodies Pre- and Post-vaccination With Fluzone® Vaccine. B/JIANGSU/10/2003 Post-dose	8.4 Titers Interval 7.5 to 9.3	15.3 Titers Interval 12.9 to 18.2

Adverse Events

Age 6 to 12 Weeks

Serious events: 4 serious events

Other events: 54 other events

Deaths: 0 deaths

Age 24 to 36 Weeks

Serious events: 3 serious events

Other events: 94 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Age 6 to 12 Weeks n=201 participants at risk Participants enrolled at 6 to 12 weeks of age	Age 24 to 36 Weeks n=192 participants at risk Participants enrolled at 24 to 36 weeks of age
Infections and infestations Kawasaki's disease	0.50% 1/201 • Number of events 1 • Adverse event data were collected for 6 months post-vaccination.	0.00% 0/192 • Adverse event data were collected for 6 months post-vaccination.
Respiratory, thoracic and mediastinal disorders Choking	0.50% 1/201 • Number of events 1 • Adverse event data were collected for 6 months post-vaccination.	0.00% 0/192 • Adverse event data were collected for 6 months post-vaccination.
Gastrointestinal disorders Viral gastroenteritis	0.00% 0/201 • Adverse event data were collected for 6 months post-vaccination.	0.52% 1/192 • Number of events 1 • Adverse event data were collected for 6 months post-vaccination.
Infections and infestations Cellulitis	0.00% 0/201 • Adverse event data were collected for 6 months post-vaccination.	0.52% 1/192 • Number of events 1 • Adverse event data were collected for 6 months post-vaccination.
Nervous system disorders Febrile convulsion	0.00% 0/201 • Adverse event data were collected for 6 months post-vaccination.	0.52% 1/192 • Number of events 3 • Adverse event data were collected for 6 months post-vaccination.
Infections and infestations Fever	0.50% 1/201 • Number of events 1 • Adverse event data were collected for 6 months post-vaccination.	0.00% 0/192 • Adverse event data were collected for 6 months post-vaccination.
Respiratory, thoracic and mediastinal disorders Bronchiolitis	0.50% 1/201 • Number of events 1 • Adverse event data were collected for 6 months post-vaccination.	0.00% 0/192 • Adverse event data were collected for 6 months post-vaccination.

Other adverse events

Other adverse events
Measure	Age 6 to 12 Weeks n=201 participants at risk Participants enrolled at 6 to 12 weeks of age	Age 24 to 36 Weeks n=192 participants at risk Participants enrolled at 24 to 36 weeks of age
Gastrointestinal disorders Diarrhoea	5.0% 10/201 • Number of events 11 • Adverse event data were collected for 6 months post-vaccination.	6.2% 12/192 • Number of events 13 • Adverse event data were collected for 6 months post-vaccination.
Gastrointestinal disorders Teething	0.00% 0/201 • Adverse event data were collected for 6 months post-vaccination.	8.9% 17/192 • Number of events 22 • Adverse event data were collected for 6 months post-vaccination.
General disorders Injection site haemorrhage	2.0% 4/201 • Number of events 5 • Adverse event data were collected for 6 months post-vaccination.	5.2% 10/192 • Number of events 11 • Adverse event data were collected for 6 months post-vaccination.
General disorders Pyrexia	2.5% 5/201 • Number of events 6 • Adverse event data were collected for 6 months post-vaccination.	9.9% 19/192 • Number of events 20 • Adverse event data were collected for 6 months post-vaccination.
Infections and infestations Nasopharyngitis	1.00% 2/201 • Number of events 2 • Adverse event data were collected for 6 months post-vaccination.	5.7% 11/192 • Number of events 12 • Adverse event data were collected for 6 months post-vaccination.
Infections and infestations Otitis media	1.5% 3/201 • Number of events 3 • Adverse event data were collected for 6 months post-vaccination.	8.3% 16/192 • Number of events 18 • Adverse event data were collected for 6 months post-vaccination.
Infections and infestations Upper respiratory tract infection	6.5% 13/201 • Number of events 13 • Adverse event data were collected for 6 months post-vaccination.	9.9% 19/192 • Number of events 20 • Adverse event data were collected for 6 months post-vaccination.
Respiratory, thoracic and mediastinal disorders Cough	4.0% 8/201 • Number of events 8 • Adverse event data were collected for 6 months post-vaccination.	8.3% 16/192 • Number of events 17 • Adverse event data were collected for 6 months post-vaccination.
Respiratory, thoracic and mediastinal disorders Nasal congestion	6.5% 13/201 • Number of events 14 • Adverse event data were collected for 6 months post-vaccination.	1.6% 3/192 • Number of events 3 • Adverse event data were collected for 6 months post-vaccination.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	4.5% 9/201 • Number of events 10 • Adverse event data were collected for 6 months post-vaccination.	7.8% 15/192 • Number of events 17 • Adverse event data were collected for 6 months post-vaccination.
Skin and subcutaneous tissue disorders Rash	2.0% 4/201 • Number of events 5 • Adverse event data were collected for 6 months post-vaccination.	5.2% 10/192 • Number of events 11 • Adverse event data were collected for 6 months post-vaccination.

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