Phase IV Trial to Collect Safety Data and Sera for Immunogenicity Testing in Healthy Children Given Fluzone® Vaccine
Sponsor
Sanofi Pasteur, a Sanofi Company (Industry)
Overall Status
Completed
CT.gov ID
NCT00561002
Collaborator
(none)
34
1
2
8
4.2
Study Details
Study Description
Brief Summary
To provide Centers for Biologic Evaluation and Research (CBER) with sera collected from healthy children receiving the 2007-2008 formulation of the inactivated, split-virion influenza vaccine Fluzone® for further study.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
34 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
Annual Study for Serum Collection and Evaluation of Safety and Immunogenicity Among Healthy Children Receiving Fluzone® Influenza Virus Vaccine (2007-2008 Formulation)
Study Start Date
:
Oct 1, 2007
Actual Primary Completion Date
:
May 1, 2008
Actual Study Completion Date
:
Jun 1, 2008
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Biological: 2007-2008 Influenza Virus Vaccine
0.25 mL, Intramuscular
Other Names:
|
| Experimental: 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. |
Biological: 2007-2008 Influenza Virus Vaccine
0.25 mL, Intramuscular
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants Who Had Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone 2007-2008 Formulation [Days 0-3 post-dose]
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.
Other Outcome Measures
- Geometric Mean Titers (GMTs) of Hemagglutinin Antibodies Pre- and Post-Fluzone® Vaccination [Day 0 and Day 14 after last dose of Fluzone]
- Percentage of Participants With at Least a 40 Serum Hemagglutination Inhibition Antibody Titers Post-Vaccination (Seroprotection) [Day 14 post-vaccination]
Seroprotection was defined as a serum hemagglutination inhibition antibody titer ≥40.
- Seroconversion Rates for Each Influenza Antigen Post-Vaccination [Day 14 post-vaccination]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
6 Months
to 35 Months
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
-
Participant is aged ≥ 6 months (24 weeks) to < 36 months (3rd birthday).
-
Participant is considered to be in good health on the basis of reported medical history and limited physical examination.
-
Participant is available for the duration of the study.
-
Parent/legal acceptable representative is willing and able to provide informed consent.
-
Parent/legal acceptable representative is willing and able to meet protocol requirements.
-
Born at full term of pregnancy (≥ 37 weeks) with a birth weight ≥ 2.5 kg (5.5 lbs).
Exclusion Criteria:
-
Reported allergy to egg proteins, chicken proteins, or any other constituent of the vaccine.
-
An acute illness with or without fever (For infants/toddlers: temperature ≥ 100.4°F rectal; For children: temperature ≥ 99.5°F oral/axillary) in the 72 hours preceding enrollment in the trial (Enrollment may be deferred).
-
Clinically significant findings in vital signs or review of systems (Investigator judgment; defer or exclude).
-
Participation in any other interventional clinical trial within 30 days prior to enrollment or planned participation in the study.
-
Known or suspected impairment of immunologic function, or receipt of immunosuppressive therapy or immunoglobulin since birth.
-
Personal or immediate family history of congenital immune deficiency.
-
Developmental delay, neurologic disorder, or seizure disorder.
-
Chronic medical, congenital, or developmental disorder.
-
Known human immunodeficiency virus (HIV)-positive mother.
-
Prior personal history of Guillain-Barré syndrome.
-
Any condition which, in the opinion of the Investigator, would pose a health risk to the subject or interfere with the evaluation of the vaccine.
-
Received any vaccinations within the preceding 14 days (enrollment may be deferred).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Norfolk | Virginia | United States |
Sponsors and Collaborators
- Sanofi Pasteur, a Sanofi Company
Investigators
- Study Director: Medical Director, Sanofi Pasteur Inc.
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Sanofi Pasteur, a Sanofi Company
ClinicalTrials.gov Identifier:
NCT00561002
Other Study ID Numbers:
- GRC38
First Posted:
Nov 20, 2007
Last Update Posted:
Apr 14, 2016
Last Verified:
Apr 1, 2016
Keywords provided by Sanofi Pasteur, a Sanofi Company
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The study participants were enrolled from 29 October 2007 through 27 November 2007 at 1 US site. |
|---|---|
| Pre-assignment Detail | 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 Participants | 23 | 9 | 32 |
| Age (Count of Participants) | |||
| <=18 years |
23
100%
|
9
100%
|
32
100%
|
| Between 18 and 65 years |
0
0%
|
0
0%
|
0
0%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
| Age (Months) [Mean (Standard Deviation) ] | |||
| Age Continuous |
19.8
(8.76)
|
24.5
(5.10)
|
21.2
(8.11)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
13
56.5%
|
4
44.4%
|
17
53.1%
|
| Male |
10
43.5%
|
5
55.6%
|
15
46.9%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
23
100%
|
9
100%
|
32
100%
|
Outcome Measures
| 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. |
| Measure Participants | 23 | 9 |
| Any Solicited Injection Site Reaction Post-dose 1 |
13
56.5%
|
4
44.4%
|
| Any Tenderness |
9
39.1%
|
2
22.2%
|
| Grd 3 Tenderness (Cries when limb is moved) |
0
0%
|
0
0%
|
| Any Pain |
3
13%
|
2
22.2%
|
| Grd 3 Pain (Incapacitating) |
0
0%
|
0
0%
|
| Any Redness (> 0.5 cm) |
3
13%
|
0
0%
|
| Grade 3 Redness (≥ 5.0 cm) |
0
0%
|
0
0%
|
| Any Swelling (> 0.5 cm) |
2
8.7%
|
0
0%
|
| Grade 3 Swelling (≥ 5.0 cm) |
0
0%
|
0
0%
|
| Any Solicited Injection Site Reaction Post-dose 2 |
7
30.4%
|
0
0%
|
| Any Tenderness |
6
26.1%
|
0
0%
|
| Grd 3 Tenderness (Cries when limb is moved) |
1
4.3%
|
0
0%
|
| Any Pain |
1
4.3%
|
0
0%
|
| Grd 3 Pain (Incapacitating) |
0
0%
|
0
0%
|
| Any Redness (> 0.5 cm) |
0
0%
|
0
0%
|
| Grade 3 Redness) (≥ 5.0 cm) |
0
0%
|
0
0%
|
| Any Swelling (> 0.5 cm) |
0
0%
|
0
0%
|
| Grade 3 Swelling (≥ 5.0 cm) |
0
0%
|
0
0%
|
| Any Solicited Injection Reaction - Any dose |
14
60.9%
|
4
44.4%
|
| Any Tenderness |
10
43.5%
|
2
22.2%
|
| Grade 3 Tenderness (Cries when limb moved) |
1
4.3%
|
0
0%
|
| Any Pain |
3
13%
|
2
22.2%
|
| Grade 3 Pain (Incapacitating) |
0
0%
|
0
0%
|
| Any Redness (> 0.5 cm) |
3
13%
|
0
0%
|
| Grade 3 Redness (≥ 5.0 cm) |
0
0%
|
0
0%
|
| Any Swelling (> 0.5 cm) |
2
8.7%
|
0
0%
|
| Grade 3 Swelling (≥ 5.0 cm) |
0
0%
|
0
0%
|
| Any Solicited Systemic Reaction Post-dose 1 |
14
60.9%
|
6
66.7%
|
| Any Fever |
4
17.4%
|
2
22.2%
|
| Grade 3 Fever (>103.1 ºF) |
1
4.3%
|
0
0%
|
| Any Vomiting |
1
4.3%
|
0
0%
|
| Grade 3 Vomiting (≥ episodes per 24 hr) |
0
0%
|
0
0%
|
| Any Abnormal Crying |
9
39.1%
|
2
22.2%
|
| Grade 3 Abnormal Crying (> 3 hr) |
0
0%
|
0
0%
|
| Any Drowsiness |
7
30.4%
|
3
33.3%
|
| Grade 3 Drowsiness (Sleeps most of the time) |
0
0%
|
0
0%
|
| Any Loss of Appetite |
7
30.4%
|
1
11.1%
|
| Grade 3 Loss of Appetite (Refuses most feeds) |
0
0%
|
0
0%
|
| Any Irritability |
11
47.8%
|
3
33.3%
|
| Grade 3 Irritability (Inconsolable) |
1
4.3%
|
0
0%
|
| Any Headache |
0
0%
|
0
0%
|
| Grade 3 Headache (Prevents daily activities) |
0
0%
|
0
0%
|
| Any Myalgia |
2
8.7%
|
0
0%
|
| Grade 3 Myalgia (Prevents daily activities) |
0
0%
|
0
0%
|
| Any Malaise |
3
13%
|
3
33.3%
|
| Grade 3 Malaise (Prevents daily activities) |
0
0%
|
0
0%
|
| Any Solicited Systemic Reaction Post-dose 2 |
11
47.8%
|
0
0%
|
| Any Fever |
3
13%
|
0
0%
|
| Grade 3 Fever (> 103ºF) |
0
0%
|
0
0%
|
| Any Vomiting |
0
0%
|
0
0%
|
| Grade 3 Vomiting (≥ 6 episodes per 24 hr) |
0
0%
|
0
0%
|
| Any Abnormal Crying |
5
21.7%
|
0
0%
|
| Grade 3 Abnormal Crying (>3 hr) |
0
0%
|
0
0%
|
| Any Drowsiness |
5
21.7%
|
0
0%
|
| Grade 3 Drowsiness (Sleeps most of time) |
0
0%
|
0
0%
|
| Any Loss of Appetite |
3
13%
|
0
0%
|
| Grade 3 Loss of Appetite (Refuses most feeds) |
0
0%
|
0
0%
|
| Any Irritability |
7
30.4%
|
0
0%
|
| Grade 3 Irritability (Inconsolable) |
0
0%
|
0
0%
|
| Any Headache |
0
0%
|
0
0%
|
| Grade 3 Headache (Prevents daily activities) |
0
0%
|
0
0%
|
| Any Myalgia |
1
4.3%
|
0
0%
|
| Grade 3 Myalgia (Prevents daily activities) |
0
0%
|
0
0%
|
| Any Malaise |
1
4.3%
|
0
0%
|
| Grade 3 Malaise (Prevents daily activities) |
0
0%
|
0
0%
|
| Any Solicited Systemic Reaction (Any dose) |
16
69.6%
|
6
66.7%
|
| Any Fever |
6
26.1%
|
2
22.2%
|
| Grade 3 Fever (> 103.1 ºF) |
1
4.3%
|
0
0%
|
| Any Vomiting |
1
4.3%
|
0
0%
|
| Grade 3 Vomiting (≥ 6 episodes per 24 hr) |
0
0%
|
0
0%
|
| Any Abnormal Crying |
10
43.5%
|
2
22.2%
|
| Grade 3 Abnormal Crying (> 3 hr) |
0
0%
|
0
0%
|
| Any Drowsiness |
8
34.8%
|
3
33.3%
|
| Grade 3 Drowsiness (Sleeps most of the time) |
0
0%
|
0
0%
|
| Any Loss of Appetite |
9
39.1%
|
1
11.1%
|
| Grade 3 Loss of Appetite (Refuses most feeds) |
0
0%
|
0
0%
|
| Any Irritability |
12
52.2%
|
3
33.3%
|
| Grade 3 Irritability (Inconsolable) |
1
4.3%
|
0
0%
|
| Any Headache |
0
0%
|
0
0%
|
| Grade 3 Headache (Prevents activities) |
0
0%
|
0
0%
|
| Any Myalgia |
2
8.7%
|
0
0%
|
| Grade 3 Myalgia (Prevents activities) |
0
0%
|
0
0%
|
| Any Malaise |
3
13%
|
3
33.3%
|
| Grade 3 Malaise (Prevents activities) |
0
0%
|
0
0%
|
| Title | Geometric Mean Titers (GMTs) of Hemagglutinin Antibodies Pre- and Post-Fluzone® Vaccination |
|---|---|
| Description | |
| 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. |
| Measure Participants | 16 | 6 |
| A/Solomon Islands/3/2006 IVR-145 (H1N1) Pre-dose |
8.31
|
5.61
|
| A/Solomon Islands/3/2006 IVR-145 (H1N1) Post-dose |
397
|
180
|
| A/Wisconsin/67/2005 (X-161B) (H3N2) Pre-dose |
10.7
|
59.9
|
| Wisconsin/67/2005 (X161B) (H3N2) Post-dose |
260
|
479
|
| B/Malaysia Split/2506/2004 Pre-dose |
12.3
|
13.3
|
| B/Malaysia Split/2506/2004 Post-dose |
186
|
180
|
| 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. |
| Measure Participants | 16 | 6 |
| A/Solomon Islands/3/2006 IVR-145 (H1N1) |
100
434.8%
|
83
922.2%
|
| A/Wisconsin/67/2005 (X-161B) (H3N2) |
100
434.8%
|
100
1111.1%
|
| B/Malaysia Split/2506/2004 |
81
352.2%
|
100
1111.1%
|
| 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. |
| Measure Participants | 16 | 6 |
| A/Solomon Islands/3/2006 IVR-145 (H1N1) |
100
434.8%
|
83
922.2%
|
| A/Wisconsin/67/2005 (X-161B) (H3N2) |
79
343.5%
|
67
744.4%
|
| B/Malaysia Split/2506/2004 |
80
347.8%
|
100
1111.1%
|
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 | ||||
| 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 (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Influenza Vaccine Naive/Inadequately Primed | Influenza Vaccine Primed | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/23 (0%) | 0/9 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Influenza Vaccine Naive/Inadequately Primed | Influenza Vaccine Primed | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 12/23 (52.2%) | 3/9 (33.3%) | ||
| General disorders | ||||
| Injection site tenderness | 10/23 (43.5%) | 2/9 (22.2%) | ||
| Injection site pain | 3/23 (13%) | 2/9 (22.2%) | ||
| Injection site redness | 3/23 (13%) | 0/9 (0%) | ||
| Injection site swelling | 2/23 (8.7%) | 0/9 (0%) | ||
| Pyrexia | 6/23 (26.1%) | 2/9 (22.2%) | ||
| Malaise | 3/23 (13%) | 3/9 (33.3%) | ||
| Metabolism and nutrition disorders | ||||
| Anorexia | 9/23 (39.1%) | 1/9 (11.1%) | ||
| Nervous system disorders | ||||
| Somnolence | 8/23 (34.8%) | 3/9 (33.3%) | ||
| Psychiatric disorders | ||||
| Crying | 10/23 (43.5%) | 2/9 (22.2%) | ||
| Irritability | 12/23 (52.2%) | 3/9 (33.3%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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. |
| Phone | |
| RegistryContactUs@sanofipasteur.com |
Responsible Party:
Sanofi Pasteur, a Sanofi Company
ClinicalTrials.gov Identifier:
NCT00561002
Other Study ID Numbers:
- GRC38
First Posted:
Nov 20, 2007
Last Update Posted:
Apr 14, 2016
Last Verified:
Apr 1, 2016