Pediatric Safety and Immunogenicity Study of Cell-Culture Derived and Egg-based Subunit Influenza Vaccines in Healthy Children and Adolescents
Sponsor
Novartis (Industry)
Overall Status
Completed
CT.gov ID
NCT00645411
Collaborator
Novartis Vaccines (Industry)
3,604
60
4
9
60.1
6.7
Study Details
Study Description
Brief Summary
The present study is the first study designed to evaluate safety, tolerability and immunogenicity of the cell culture-derived influenza vaccine in healthy children and adolescents aged 3 to 17 years. A step-down approach is utilized in which reactogenicity and safety will be assessed in children and adolescents 9 to 17 years of age (Cohort 1) prior to enrolling additional children and adolescents 9 to 17 years of age (Cohort 2) and children 3 to 8 years of age (Cohort 3).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
3604 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Participant)
Primary Purpose:
Prevention
Official Title:
A Combined Phase II/III, Observer-Blind, Randomized, Multi-center Study to Evaluate Safety, Tolerability and Immunogenicity of Trivalent Subunit Influenza Vaccines, Produced Either in Mammalian Cell Culture or in Embryonated Hen Eggs, in Healthy Children and Adolescents
Study Start Date
:
Oct 1, 2007
Actual Primary Completion Date
:
Feb 1, 2008
Actual Study Completion Date
:
Jul 1, 2008
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohorts 1 + Cohort 2 (9-17 Yrs) cTIV All subjects received one 0.5 mL IM injection, of cell culture-derived trivalent influenza vaccine containing 15μg of HA for each strain (A/Solomon Islands/3/2006 [H1N1]-like, A/Wisconsin/67/2005 [H3N2]-like, and B/Malaysia/ 2506/2004-like), recommended for the 2007-2008 influenza season in the Northern Hemisphere |
Biological: Cell culture-derived influenza subunit vaccine (cTIV)
One 0.5 ml injection of the cell culture-derived influenza vaccine in the deltoid muscle, preferably of the nondominant arm.
|
| Active Comparator: Cohorts 1 + Cohort 2 (9-17 Yrs) eTIV All subjects received one 0.5 mL injection, of egg -derived trivalent influenza vaccine containing 15μg of HA for each strain (A/Solomon Islands/3/2006 [H1N1]-like, A/Wisconsin/67/2005 [H3N2]-like and B/Malaysia/ 2506/2004-like), recommended for the 2007-2008 influenza season in the Northern Hemisphere. |
Biological: Egg derived influenza subunit vaccine (eTIV)
One 0.5 ml injection of the conventional egg-derived influenza vaccine in the deltoid muscle, preferably of the nondominant arm.
|
| Experimental: Cohort 3 (3-8 Yrs) cTIV All subjects received two 0.5 mL injections, administered four weeks apart, of cell culture-derived trivalent influenza vaccine containing 15μg of HA for each strain (A/Solomon Islands/3/2006 [H1N1]-like, A/Wisconsin/67/2005 [H3N2]-like and B/Malaysia/ 2506/2004-like), recommended for the 2007-2008 influenza season in the Northern Hemisphere |
Biological: Cell culture-derived influenza subunit vaccine (cTIV)
Two 0.5 mL injections,of the cell culture-derived influenza vaccine in the deltoid muscle, preferably of the nondominant arm, administered four weeks apart.
|
| Active Comparator: Cohort 3 (3-8 Yrs) eTIV All subjects received two 0.5 mL injections, administered four weeks apart of egg -derived trivalent influenza vaccine containing 15μg of HA for each strain (A/Solomon Islands/3/2006 [H1N1]-like, A/Wisconsin/67/2005 [H3N2]-like and B/Malaysia/ 2506/2004-like), recommended for the 2007-2008 influenza season in the Northern Hemisphere |
Biological: Egg derived influenza subunit vaccine (eTIV)
Two 0.5 mL injections of the conventional egg-derived influenza vaccine in the deltoid muscle, preferably of the nondominant arm,administered four weeks apart.
|
Outcome Measures
Primary Outcome Measures
- Geometric Mean Titers of the Cell Culture-derived Vaccine Compared With the Egg-derived Vaccine in 3 to 8 Year-old Children [Day 50 post vaccination]
To demonstrate non-inferiority of the post vaccination hemagglutination inhibition (HI) geometric mean titer (GMT) of the cell culture-derived influenza (cTIV) vaccine to the corresponding GMT of the egg-derived (eTIV) influenza vaccine, for all three strains, after two injections administered four weeks apart to a subset of children 3 to 8 years of age. GMTs were evaluated using two assays, HI egg derived antigen assay and HI cell derived antigen assay.
- Percentages of Subjects Who Attained Seroconversion or Significant Increase in Antibody Titers in the Cell Culture-derived Vaccine Compared With the Egg-derived Vaccine in 3 to 8 Year-old Children [Day 50 post vaccination]
To demonstrate non-inferiority of the cell culture-derived influenza (cTIV) vaccine to the egg-derived (eTIV) influenza vaccine in the percentage of subjects achieving seroconversion or significant increase in antibody titer post vaccination, for all three strains, after two injections administered four weeks apart in children 3 to 8 years of age. Seroconversion rate was evaluated using two assays- HI egg derived antigen assay and HI cell derived antigen assay.
Secondary Outcome Measures
- Geometric Mean Titers After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents [Day 29 post vaccination]
To evaluate immunogenicity in terms of Geometric Mean Titers (GMTs) in children 9 to 17 years of age after one injection of either cTIV vaccine or eTIV. GMTs were evaluated using two assays, HI egg derived antigen assay and HI cell derived antigen assay.
- Geometric Mean Ratio After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents. [Day 29 post vaccination]
Immunogenicity was evaluated in terms of Geometric Mean Ratio (GMRs) in 9 to 17 year-old children and adolescents after one injection of either cTIV vaccine or eTIV. The criterion is met according to European (CHMP) guideline if the mean geometric increase GMR (day29/day1) in HI antibody titer is >2.5.
- Percentages of Subjects Who Achieved HI Titers ≥40 After 1 Dose of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents [Day 29 post vaccination]
To evaluate immunogenicity in terms of percentage of 9 to 17 year-old children and adolescents achieving HI titers ≥40, after one injection of either the cTIV vaccine or the eTIV vaccine. This criterion is met according to European (CHMP) guideline if the percentage of subjects achieving HI titers ≥40 is >70% and according to the US (CBER) guideline is met if the lower bound of the two sided 95%CI for percentage of subjects achieving HI titers ≥40 is ≥70%.
- Percentages of Subjects Who Attained Seroconversion or Significant Increase After 1 Dose of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents [Day 29 post vaccination]
Seroconversion or significant increase as per CHMP criteria is defined as percentage of subjects with a pre vaccination HI titer <10 to a post vaccination titer ≥40 or a pre vaccination HI titer ≥10 and a ≥4-fold increase in post vaccination HI antibody titer. According to the CHMP criteria, the percentage of subjects achieving seroconversion or significant increase should be >40%. According to the CBER criteria, the lower bound of the two-sided 95% CI for the percentage of subjects achieving seroconversion/significant increase should be ≥40%.
- Geometric Mean Titers After Two Doses of the Cell Derived or the Egg Derived Vaccine in 3 to 8 Year-old Children [Day 29 and Day 50 post vaccination]
To evaluate immunogenicity in terms of Geometric Mean Titers (GMTs) in children 3 to 8 years of age after two doses of either cTIV vaccine or eTIV,administered 4 weeks apart.
- Geometric Mean Ratio After Two Doses of the Cell-derived or the Egg-derived Vaccine in 3 to 8 Year-old Children [Day 29 and Day 50 post vaccination]
To evaluate immunogenicity in terms of Geometric Mean Ratio (GMR) in children 3 to 8 years of age after two doses of either the cTIV vaccine or the eTIV vaccine, administered 4 weeks apart according to the CHMP criteria. The criterion is met according to the European (CHMP) guideline if the mean geometric increase (GMR day 29/day 1 and GMR day 50/day 1) in HI antibody titer is >2.5
- Percentages of Subjects Who Achieved HI Titers ≥40 After Two Doses of the Cell Culture Derived or the Egg Derived Influenza Vaccine in 3 to 8 Year-old Children [Day 29 and Day 50 post vaccination]
To evaluate immunogenicity in terms of HI titers ≥40, in children 3-8 years of age after two doses of either cTIV vaccine or eTIV vaccine, administered 4 weeks apart. The criterion is met according to European (CHMP) guideline if the percentage of subjects achieving HI titers ≥40 is >70% and according to the US (CBER) guideline if the lower bound of the two sided 95%CI for percentage of subjects achieving HI titers ≥40 is ≥70%.
- Percentages of Subjects Who Achieved Seroconversion or Significant Increase in HI Titers After Two Doses of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 3 to 8 Year-old Children [Day 29 and Day 50 post vaccination]
Seroconversion or significant increase as per CHMP criteria is defined as percentage of subjects with a pre vaccination HI titer <10 to a post vaccination titer ≥40 or a pre vaccination HI titer ≥10 and a ≥4-fold increase in post vaccination HI antibody titer. According to the CHMP criteria, the percentage of subjects achieving seroconversion or significant increase should be >40%. According to the CBER criteria, the lower bound of the two-sided 95% CI for the percentage of subjects achieving seroconversion/significant increase should be ≥40%.
- Number of Subjects Reporting Local and Systemic Reactions After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents. [up to 7 days after vaccination]
To evaluate safety and tolerability in terms of number of 9 to 17 year-old children and adolescents (cohorts 1 and 2) reporting local and systemic reactions following of one injection of the cTIV or the eTIV vaccine .
- Number of Subjects Reporting Local and Systemic Reactions After One and Two Doses of the Cell Culture-derived Vaccine or Egg-derived Influenza Vaccine in 3 to 8 Year-old Children. [up to 7 days after each vaccination]
To evaluate the safety and tolerability of the cTIV and the eTIV influenza vaccines in 3 to 8 year-old children terms of number of participants reporting local and systemic reactions after each vaccination.
Eligibility Criteria
Criteria
Ages Eligible for Study:
3 Years
to 17 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
-
Subjects aged 9 to 17 years (Cohorts 1 and 2) and 3 to 8 years (Cohort 3), whose parents/legal guardians have given written informed consent prior to study entry. Assent will be obtained from subjects according to age requirements of the ECs/IRBs;
-
In good health as determined by:
-
medical history,
-
physical examination,
-
clinical judgment of the Investigator;
-
Able to comply with all study procedures and available for all clinic visits and telephone calls scheduled in the study.
Exclusion Criteria:
-
Any serious disease, such as:
-
cancer,
-
autoimmune disease (including rheumatoid arthritis),
-
diabetes mellitus,
-
chronic pulmonary disease,
-
acute or progressive hepatic disease,
-
acute or progressive renal disease;
-
History of any anaphylaxis or serious reaction following administration of vaccine, or hypersensitivity to eggs, egg protein, chicken feathers, influenza viral protein, neomycin, polymyxin, or any other vaccine component, chemically related substance, or component of the potential packaging materials;
-
Known or suspected impairment/alteration of immune function, including:
-
use of immunosuppressive therapy such as systemic corticosteroids known to be associated with the suppression of hypothalamic-pituitary-adrenal (HPA) axis or chronic use of inhaled high-potency corticosteroids within 60 days prior to Visit 1,
-
cancer chemotherapy,
-
receipt of immunostimulants within 60 days prior to Visit 1,
-
receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivatives within 3 months prior to Visit 1 or planned during the full length of the study,
-
known HIV infection or HIV-related disease;
-
History of Guillain-Barré syndrome;
-
Bleeding diathesis;
-
Surgery planned during the study period;
-
Receipt of another investigational agent within 90 days, or before completion of the safety follow-up period in another study, whichever is longer, prior to enrollment and unwilling to refuse participation in another clinical study through the end of the study;
-
Receipt of another vaccine within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to Visit 1;
-
Laboratory-confirmed influenza disease within 6 months prior to Visit 1;
-
For subjects aged 3 to 8 years old, ever received two doses of an influenza vaccine in one influenza season;
-
Receipt of an influenza vaccine within 6 months prior to Visit 1;
-
Experienced a temperature 38.0°C [100.4°F]) and/or any acute illness within 3 days prior to Visit 1;
-
Pregnant or nursing mother;
-
Female of childbearing potential who is sexually active and has not used acceptable birth control measures for at least 2 months prior to study entry and who does not plan to use acceptable birth control measures during the 3 weeks following vaccination or refuses to have a urine pregnancy test prior to enrollment. Oral, injected, inserted or implanted hormonal contraceptive, diaphragm or condom with spermicidal agent or intrauterine device are considered acceptable forms of birth control;
-
Children of research staff or those living with research staff directly involved with the clinical study. Research staff are individuals with direct study subject contact, indirect contact with study subjects, or study site personnel who have access to any study documents containing subject information. This would include receptionists, persons scheduling appointments or making screening calls, regulatory specialists, laboratory technicians, etc.;
-
Any condition, which in the opinion of the Investigator, might interfere with the evaluation of the study objectives.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Site 09 | Fayetteville | Arkansas | United States | 72703 |
| 2 | Site 10 | Downey | California | United States | 90241 |
| 3 | Site 02 | Bardstown | Kentucky | United States | 40004 |
| 4 | Site 14 | Metairie | Louisiana | United States | 70006 |
| 5 | Site 01 | St. Louis | Missouri | United States | 63104 |
| 6 | Site 11 | Omaha | Nebraska | United States | 68134 |
| 7 | Site 04 | Edison | New Jersey | United States | 08817 |
| 8 | Site 05 | Endwell | New York | United States | 13760 |
| 9 | Site 16 | Fort Worth | Texas | United States | 76135 |
| 10 | Site 13 | San Angelo | Texas | United States | 76904 |
| 11 | Site 12 | San Antonio | Texas | United States | 78205 |
| 12 | Site 08 | Bountiful | Utah | United States | 84010 |
| 13 | Site 07 | Salt Lake City | Utah | United States | 84109 |
| 14 | Site 03 | Salt Lake City | Utah | United States | 84121 |
| 15 | Site 06 | Burke | Virginia | United States | 22105 |
| 16 | Site 15 | Spokane | Washington | United States | 99202 |
| 17 | Site 44:Spec. Pediatric Dispensary | Dakovo | Croatia | ||
| 18 | Site 83 | Ljudevita Gaja 2, Djakovo | Croatia | ||
| 19 | Site 43: Spec. Pediatric Dispensary | Sisak | Croatia | ||
| 20 | Site 27:Institute of Public Health | Zagreb | Croatia | ||
| 21 | Site 29: Institute of Public Health | Zagreb | Croatia | ||
| 22 | Site 40:Spec. Pediatric Dispensary | Zagreb | Croatia | ||
| 23 | Site 49: Spec. Pediatric Dispensary | Zagreb | Croatia | ||
| 24 | Site 50: Spec. Pediatric Dispensary | Zagreb | Croatia | ||
| 25 | Site 86: Spec. Pediatric Dispensary | Zagreb | Croatia | ||
| 26 | Site 70: Espoon rokotetutkimusklinikka | Heikintori | Espoo | Finland | 02100 |
| 27 | Site 79: Kokkola Vaccine Research Clinic | Rantakatu 7 | Kokkola | Finland | 67100 |
| 28 | Site 78: Kuopio Vaccine Research Clinic | Microkatu 1,Osa/Section A, 3rd floor PL1188 | Kuopio | Finland | 70211 |
| 29 | Site 71: Etelä-Helsingin rokotetutkimusklinikka | Helsinki | Finland | 00100 | |
| 30 | Site 72: Itä-Helsingin rokotetutkimusklinikka | Helsinki | Finland | 00930 | |
| 31 | Site 76: Järvenpään rokotetutkimusklinikka | Järvenpää | Finland | 04400 | |
| 32 | Site 77: Kotkan rokotetutkimusklinikka | Kotka | Finland | 48600 | |
| 33 | Site 67: Lahden rokotetutkimusklinikka | Lahti | Finland | 15140 | |
| 34 | Site 75: Oulun rokotetutkimusklinikka | Oulu | Finland | 90100 | |
| 35 | Site 68: Porin rokotetutkimusklinikka | Pori | Finland | 28120 | |
| 36 | Site 66: Tampereen rokotetutkimusklinikka | Tampere | Finland | 33100 | |
| 37 | Site 69: Turun rokotetutkimusklinikka | Turku | Finland | 20520 | |
| 38 | Site 73: Itä-Vantaan rokotetutkimusklinikka | Vantaa | Finland | 01300 | |
| 39 | Site 74: Länsi-Vantaan rokotetutkimusklinikka | Vantaa | Finland | 01600 | |
| 40 | Site 57: Házi Gyermekorvosi Rendelő | Budapest | Hungary | 1042 | |
| 41 | Site 53: Heim Pál Gyermekkórház | Budapest | Hungary | 1089 | |
| 42 | Site 52: Ferencvárosi Gyermekorvos Kft. | Budapest | Hungary | 1097 | |
| 43 | Site 56: Házi Gyermekorvosi Rendelő | Budapest | Hungary | 1136 | |
| 44 | Site 54: Házi Gyermekorvosi Rendelő | Budapest | Hungary | 1173 | |
| 45 | Site 51: 5053. számú Gyermekorvosi Rendelő | Miskolc | Hungary | 3534 | |
| 46 | Site 55: Revamed kft. | Nyíregyháza | Hungary | 4481 | |
| 47 | Site 59: Vas Megyei Markusovszky Lajos, Általános, Rehabilitációs és Gyógyfürdő Kórház, Egyetemi Oktató Kórház | Szombathely | Hungary | 9700 | |
| 48 | Site 42: Dipartimento di Medicina Clinica e Sperimentale - Sezione di Igiene e Medicina Preventiva | Ferrara | Italy | 44100 | |
| 49 | Site 47: Dipartimento Scienze della Salute, Sezione di Igiene e Medicina Preventiva, Univesità di Genova | Genova | Italy | 16132 | |
| 50 | Site 41: Ospedale Maggiore della Carità-Clinica Pediatrica | Novara | Italy | 28100 | |
| 51 | Site 46: USL 2 Perugia, Distretto del perugino, Centro di Salute n. 4 (Madonna Alta) e n. 6 (Ellera di Corciano del distretto del perugino) | Perugia | Italy | 06070 | |
| 52 | Site 45: AUSL 7 | Ragusa | Italy | 97100 | |
| 53 | Site 35 | Kaunas | Lithuania | 48259 | |
| 54 | Site 36 | Vilnius | Lithuania | 01117 | |
| 55 | Site 32 | Vilnius | Lithuania | 02169 | |
| 56 | Site 34 | Vilnius | Lithuania | 04318 | |
| 57 | Site 31 | Vilnius | Lithuania | 10207 | |
| 58 | Site 33 | Vilnius | Lithuania | 11200 | |
| 59 | Site 25 | Campulung Muscel | Arges | Romania | 115100 |
| 60 | Site 21 | Craiova | Dolj | Romania | 200642 |
Sponsors and Collaborators
- Novartis
- Novartis Vaccines
Investigators
- Study Chair: Novartis Vaccines, Novartis Vaccines
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Novartis
ClinicalTrials.gov Identifier:
NCT00645411
Other Study ID Numbers:
- V58P12
- Eudract Number: 2007-001534-13
First Posted:
Mar 27, 2008
Last Update Posted:
Nov 23, 2015
Last Verified:
Oct 1, 2015
Keywords provided by Novartis
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants were enrolled from 14 sites in Finland, 16 in the US, 9 in Croatia, 5 in Italy, 6 in Lithuania, 2 in Romania, 8 in Hungary. |
|---|---|
| Pre-assignment Detail | All subjects enrolled were included in the trial. |
| Arm/Group Title | Cohort 1+2 cTIV (9-17 Years) | Cohort 1+2 eTIV (9-17 Years) | Cohort 3 cTIV (3-8 Years) | Cohort 3 eTIV (3-8 Years) |
|---|---|---|---|---|
| Arm/Group Description | All subjects aged 9-17 years received one 0.5 mL injection, of Cell Culture-derived trivalent influenza vaccine. | All subjects aged 9-17 years received one 0.5 mL injection, of egg -derived trivalent influenza vaccine. | All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart, of Cell Culture-derived trivalent influenza vaccine. | All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart of egg-derived trivalent influenza vaccine. |
| Period Title: Overall Study | ||||
| STARTED | 656 | 318 | 1608 | 1022 |
| COMPLETED | 643 | 312 | 1457 | 919 |
| NOT COMPLETED | 13 | 6 | 151 | 103 |
Baseline Characteristics
| Arm/Group Title | Cohort 1+2 cTIV (9-17 Years) | Cohort 1+2 eTIV (9-17 Years) | Cohort 3 cTIV (3-8 Years) | Cohort 3 eTIV (3-8 Years) | Total |
|---|---|---|---|---|---|
| Arm/Group Description | All subjects aged 9-17 years received one 0.5 mL injection, of Cell Culture-derived trivalent influenza vaccine. | All subjects aged 9-17 years received one 0.5 mL injection, of egg-derived trivalent influenza vaccine. | All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart, of Cell Culture-derived trivalent influenza vaccine. | All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart of egg-derived trivalent influenza vaccine. | Total of all reporting groups |
| Overall Participants | 656 | 318 | 1608 | 1022 | 3604 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
12.6
(2.6)
|
12.6
(2.5)
|
5.5
(1.7)
|
5.4
(1.7)
|
7.4
(3.7)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
304
46.3%
|
154
48.4%
|
795
49.4%
|
494
48.3%
|
1747
48.5%
|
| Male |
352
53.7%
|
164
51.6%
|
813
50.6%
|
528
51.7%
|
1857
51.5%
|
Outcome Measures
| Title | Geometric Mean Titers of the Cell Culture-derived Vaccine Compared With the Egg-derived Vaccine in 3 to 8 Year-old Children |
|---|---|
| Description | To demonstrate non-inferiority of the post vaccination hemagglutination inhibition (HI) geometric mean titer (GMT) of the cell culture-derived influenza (cTIV) vaccine to the corresponding GMT of the egg-derived (eTIV) influenza vaccine, for all three strains, after two injections administered four weeks apart to a subset of children 3 to 8 years of age. GMTs were evaluated using two assays, HI egg derived antigen assay and HI cell derived antigen assay. |
| Time Frame | Day 50 post vaccination |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed on the per-protocol dataset |
| Arm/Group Title | Cohort 3 cTIV (3-8 Years) | Cohort 3 eTIV (3-8 Years) |
|---|---|---|
| Arm/Group Description | All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart, of Cell Culture-derived trivalent influenza vaccine. | All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart of egg - derived trivalent influenza vaccine. |
| Measure Participants | 524 | 513 |
| A/H1N1 (egg derived antigen assay) |
407
|
477
|
| A/H3N2 (egg derived antigen assay) |
768
|
1293
|
| B (egg derived antigen assay) |
25
|
44
|
| A/H1N1 (cell derived antigen assay) (N=522,513) |
563
|
610
|
| A/H3N2 (cell derived antigen assay) (N=522,513) |
858
|
1329
|
| B (cell derived antigen assay) (N=522,513) |
53
|
62
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 3 cTIV (3-8 Years), Cohort 3 eTIV (3-8 Years) |
|---|---|---|
| Comments | Non-inferiority of cTIV to eTIV against A/H1N1 influenza strain as measured by HI egg-derived antigen assay | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Cell derived vaccine was considered non-inferior to egg-derived vaccine in post vaccination HI GMTs if, for all three influenza strains, the lower limit of the two-sided 95% confidence interval (CI) for day 50 ratio of GMTs (cTIV/eTIV) was >0.667. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of GMTs |
| Estimated Value | 0.85 | |
| Confidence Interval |
(2-Sided) 95% 0.72 to 1.01 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 3 cTIV (3-8 Years), Cohort 3 eTIV (3-8 Years) |
|---|---|---|
| Comments | Non-inferiority of cTIV to eTIV against A/H3N2 influenza strain as measured by HI egg-derived antigen assay. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Cell derived vaccine (cTIV ) was considered non-inferior to egg-derived vaccine (eTIV) in postvaccination HI GMTs if, for all three influenza strains, the lower limit of the two-sided 95% confidence interval (CI) for day 50 ratio of GMTs(cTIV/eTIV) was >0.667. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of GMTs |
| Estimated Value | 0.59 | |
| Confidence Interval |
(2-Sided) 95% 0.49 to 0.72 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Cohort 3 cTIV (3-8 Years), Cohort 3 eTIV (3-8 Years) |
|---|---|---|
| Comments | Non-inferiority of cTIV to eTIV against influenza B strain as measured by HI egg-derived antigen assay. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Cell derived vaccine (cTIV ) was considered non-inferior to egg-derived vaccine (eTIV)in post vaccination HI GMTs if, for all three influenza strains, the lower limit of the two-sided 95% confidence interval (CI) for day 50 ratio of GMTs (cTIV/eTIV) was >0.667. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of GMTs |
| Estimated Value | 0.56 | |
| Confidence Interval |
(2-Sided) 95% 0.46 to 0.68 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Cohort 3 cTIV (3-8 Years), Cohort 3 eTIV (3-8 Years) |
|---|---|---|
| Comments | Non-inferiority of cTIV to eTIV against A/H1N1 influenza strain as measured by HI cell-derived antigen assay. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Cell derived vaccine (cTIV) was considered non-inferior to egg-derived vaccine (eTIV) in post vaccination HI GMTs if, for all three influenza strains, the lower limit of the two-sided 95% confidence interval (CI) for day 50 ratio of GMTs (cTIV/eTIV) was >0.667. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of GMTs |
| Estimated Value | 0.92 | |
| Confidence Interval |
(2-Sided) 95% 0.79 to 1.08 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Cohort 3 cTIV (3-8 Years), Cohort 3 eTIV (3-8 Years) |
|---|---|---|
| Comments | Non-inferiority of cTIV to eTIV against A/H3N2 influenza strain as measured by HI cell-derived antigen assay. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Cell derived vaccine (cTIV) was considered non-inferior to egg-derived vaccine (eTIV)in post vaccination HI GMTs if, for all three influenza strains, the lower limit of the two-sided 95% confidence interval (CI) for day 50 ratio of GMTs (cTIV/eTIV) was >0.667. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of GMTs |
| Estimated Value | 0.65 | |
| Confidence Interval |
(2-Sided) 95% 0.54 to 0.78 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Cohort 3 cTIV (3-8 Years), Cohort 3 eTIV (3-8 Years) |
|---|---|---|
| Comments | Non-inferiority of cTIV to eTIV against B influenza strain as measured by HI cell-derived antigen assay. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Cell derived vaccine (cTIV) was considered non-inferior to egg-derived vaccine (eTIV)in post vaccination HI GMTs if, for all three influenza strains, the lower limit of the two-sided 95% confidence interval (CI) for day 50 ratio of GMTs (cTIV/eTIV)was >0.667. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of GMTs |
| Estimated Value | 0.87 | |
| Confidence Interval |
(2-Sided) 95% 0.71 to 1.06 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentages of Subjects Who Attained Seroconversion or Significant Increase in Antibody Titers in the Cell Culture-derived Vaccine Compared With the Egg-derived Vaccine in 3 to 8 Year-old Children |
|---|---|
| Description | To demonstrate non-inferiority of the cell culture-derived influenza (cTIV) vaccine to the egg-derived (eTIV) influenza vaccine in the percentage of subjects achieving seroconversion or significant increase in antibody titer post vaccination, for all three strains, after two injections administered four weeks apart in children 3 to 8 years of age. Seroconversion rate was evaluated using two assays- HI egg derived antigen assay and HI cell derived antigen assay. |
| Time Frame | Day 50 post vaccination |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed on the per-protocol dataset |
| Arm/Group Title | Cohort 3 cTIV (3-8 Years) | Cohort 3 eTIV (3-8 Years) |
|---|---|---|
| Arm/Group Description | All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart, of Cell Culture-derived trivalent influenza vaccine. | All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart of egg-derived trivalent influenza vaccine. |
| Measure Participants | 524 | 513 |
| A/H1N1 (egg derived antigen assay) |
94
|
96
|
| A/H3N2 (egg derived antigen assay) |
77
|
86
|
| B (egg derived antigen assay) |
38
|
53
|
| A/H1N1 (cell derived antigen assay) (N=522,513) |
96
|
96
|
| A/H3N2 (cell derived antigen assay) (N=522,513) |
80
|
85
|
| B (cell derived antigen assay) (N=522,513) |
58
|
58
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 3 cTIV (3-8 Years), Cohort 3 eTIV (3-8 Years) |
|---|---|---|
| Comments | Non-inferiority of cTIV to eTIV against A/H1N1 influenza strain as measured by HI egg-derived antigen assay. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | cTIV was considered non-inferior to eTIV in terms of the percentages of subjects achieving seroconversion or significant increase in antibody titer at day 50 if for all three strains, the lower limit of the two-sided 95% CI around the differences in the percentages of subjects achieving seroconversion and significant increase (cTIV minus eTIV) was >-10%. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in % (cTIV minus eTIV) |
| Estimated Value | -1 | |
| Confidence Interval |
(2-Sided) 95% -4 to 1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 3 cTIV (3-8 Years), Cohort 3 eTIV (3-8 Years) |
|---|---|---|
| Comments | Non-inferiority of cTIV to eTIV against A/H3N2 influenza strain as measured by HI egg-derived antigen assay. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | cTIV was considered non-inferior to eTIV in terms of the percentages of subjects achieving seroconversion or significant increase in antibody titer at day 50 if for all three strains, the lower limit of the two-sided 95% CI around the differences in the percentages of subjects achieving seroconversion and significant increase (cTIV minus eTIV) was >-10%. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference % (cTIV - eTIV) |
| Estimated Value | -9 | |
| Confidence Interval |
(2-Sided) 95% -13 to -4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Cohort 3 cTIV (3-8 Years), Cohort 3 eTIV (3-8 Years) |
|---|---|---|
| Comments | Non-inferiority of cTIV to eTIV against B influenza strain as measured by HI egg-derived antigen assay. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | cTIV was considered non-inferior to eTIV in terms of the percentages of subjects achieving seroconversion or significant increase in antibody titer at day 50 if for all three strains, the lower limit of the two-sided 95% CI around the differences in the percentages of subjects achieving seroconversion and significant increase (cTIV minus eTIV) was >-10%. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference % (cTIV minus eTIV) |
| Estimated Value | -15 | |
| Confidence Interval |
(2-Sided) 95% -21 to -9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Cohort 3 cTIV (3-8 Years), Cohort 3 eTIV (3-8 Years) |
|---|---|---|
| Comments | Non-inferiority of cTIV to eTIV against A/H1N1 influenza strain as measured by HI cell-derived antigen assay. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | cTIV was considered non-inferior to eTIV in terms of the percentages of subjects achieving seroconversion or significant increase in antibody titer at day 50 if for all three strains, the lower limit of the two-sided 95% CI around the differences in the percentages of subjects achieving seroconversion and significant increase (cTIV minus eTIV) was >-10% | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference % (cTIV minus eTIV) |
| Estimated Value | -1 | |
| Confidence Interval |
(2-Sided) 95% -3 to 2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Cohort 3 cTIV (3-8 Years), Cohort 3 eTIV (3-8 Years) |
|---|---|---|
| Comments | Non-inferiority of cTIV to eTIV against A/H3N2 influenza strain as measured by HI cell-derived antigen assay. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | cTIV was considered non-inferior to eTIV in terms of the percentages of subjects achieving seroconversion or significant increase in antibody titer at day 50 if for all three strains, the lower limit of the two-sided 95% CI around the differences in the percentages of subjects achieving seroconversion and significant increase (cTIV minus eTIV) was >-10%. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference % (cTIV minus eTIV) |
| Estimated Value | -5 | |
| Confidence Interval |
(2-Sided) 95% -9.5 to 0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Cohort 3 cTIV (3-8 Years), Cohort 3 eTIV (3-8 Years) |
|---|---|---|
| Comments | Non-inferiority of cTIV to eTIV against B influenza strain as measured by HI cell-derived antigen assay. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | cTIV was considered non-inferior to eTIV in terms of the percentages of subjects achieving seroconversion or significant increase in antibody titer at day 50 if for all three strains, the lower limit of the two-sided 95% CI around the differences in the percentages of subjects achieving seroconversion and significant increase (cTIV minus eTIV) was >-10%. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference % (cTIV minus eTIV) |
| Estimated Value | 0 | |
| Confidence Interval |
(2-Sided) 95% -6 to 6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Geometric Mean Titers After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents |
|---|---|
| Description | To evaluate immunogenicity in terms of Geometric Mean Titers (GMTs) in children 9 to 17 years of age after one injection of either cTIV vaccine or eTIV. GMTs were evaluated using two assays, HI egg derived antigen assay and HI cell derived antigen assay. |
| Time Frame | Day 29 post vaccination |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed on the per-protocol dataset. |
| Arm/Group Title | Cohort 1 cTIV (9-17 Years) | Cohort 1 eTIV (9-17 Years) |
|---|---|---|
| Arm/Group Description | All subjects aged 9-17 years received one 0.5 mL injection, of Cell Culture-derived trivalent influenza vaccine | All subjects aged 9-17 years received one 0.5 mL injection, of egg-derived trivalent influenza vaccine. |
| Measure Participants | 142 | 144 |
| Baseline (A/H1N1) egg derived antigen assay |
55
|
78
|
| Day 29 (A/H1N1) egg derived antigen assay |
879
|
1107
|
| Baseline (A/H3N2) egg derived antigen assay |
121
|
151
|
| Day 29 (A/H3N2) egg derived antigen assay |
706
|
1857
|
| Baseline (B) Egg derived antigen assay |
9.65
|
9.92
|
| Day 29 (B) egg derived antigen assay |
58
|
105
|
| Baseline(A/H1N1)Cell derived assay |
70
|
90
|
| Day 29 (A/H1N1) cell derived antigen assay |
1076
|
1296
|
| Baseline(A/H3N2)cell derived assay(N=141,144) |
125
|
144
|
| Day 29 (A/H3N2) cell derived antigen assay |
676
|
1651
|
| Baseline(B)cell derived assay(N=141,144) |
22
|
25
|
| Day 29 (B) cell derived antigen assay |
136
|
186
|
| Title | Geometric Mean Ratio After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents. |
|---|---|
| Description | Immunogenicity was evaluated in terms of Geometric Mean Ratio (GMRs) in 9 to 17 year-old children and adolescents after one injection of either cTIV vaccine or eTIV. The criterion is met according to European (CHMP) guideline if the mean geometric increase GMR (day29/day1) in HI antibody titer is >2.5. |
| Time Frame | Day 29 post vaccination |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed on the per-protocol dataset. |
| Arm/Group Title | Cohort 1 cTIV (9-17 Years) | Cohort 1 eTIV (9-17 Years) |
|---|---|---|
| Arm/Group Description | All subjects aged 9-17 years received one 0.5 mL injection, of Cell Culture-derived trivalent influenza vaccine. | All subjects aged 9-17 years received one 0.5 mL injection, of egg-derived trivalent influenza vaccine. |
| Measure Participants | 142 | 144 |
| Day 29 (A/H1N1)egg derived antigen assay |
16
|
14
|
| Day 29 (A/H3N2) egg derived antigen assay |
5.84
|
12
|
| Day 29 (B) egg derived antigen assay |
6.03
|
11
|
| Day29(A/H1N1)cell derived antigen assay(N=141,144) |
15
|
14
|
| Day29(A/H3N2)cell derived antigen assay(N=141,144) |
5.45
|
11
|
| Day29(B) cell derived antigen assay(N=141,144) |
6.15
|
7.37
|
| Title | Percentages of Subjects Who Achieved HI Titers ≥40 After 1 Dose of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents |
|---|---|
| Description | To evaluate immunogenicity in terms of percentage of 9 to 17 year-old children and adolescents achieving HI titers ≥40, after one injection of either the cTIV vaccine or the eTIV vaccine. This criterion is met according to European (CHMP) guideline if the percentage of subjects achieving HI titers ≥40 is >70% and according to the US (CBER) guideline is met if the lower bound of the two sided 95%CI for percentage of subjects achieving HI titers ≥40 is ≥70%. |
| Time Frame | Day 29 post vaccination |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed on the per-protocol dataset. |
| Arm/Group Title | Cohort 1 cTIV (9-17 Years) | Cohort 1 eTIV (9-17 Years) |
|---|---|---|
| Arm/Group Description | All subjects aged 9-17 years received one 0.5 mL injection, of Cell Culture-derived trivalent influenza vaccine. | All subjects aged 9-17 years received one 0.5 mL injection, of egg-derived trivalent influenza vaccine. |
| Measure Participants | 142 | 144 |
| Prevaccination (A/H1N1)egg derived antigen assay |
65
|
75
|
| Day 29 (A/H1N1) egg derived antigen assay |
99
|
99
|
| Prevaccination (A/H3N2) egg derived antigen assay |
82
|
86
|
| Day 29 (A/H3N2) egg derived antigen assay |
100
|
100
|
| Prevaccination(B)egg derived antigen assay |
17
|
13
|
| Day 29 (B) egg derived antigen assay |
75
|
84
|
| Prevaccination (H1N1)cell derived assay(N=141,144) |
67
|
78
|
| Day 29 (A/H1N1)cell derived antigen assay |
99
|
98
|
| Prevaccination (H3N2)cell derived assay(N=141,144) |
83
|
86
|
| Day 29 (A/H3N2) cell derived antigen assay |
100
|
100
|
| Prevaccination (B) cell derived assay(N=141,144) |
40
|
47
|
| Day 29 (B) cell derived antigen assay |
95
|
94
|
| Title | Percentages of Subjects Who Attained Seroconversion or Significant Increase After 1 Dose of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents |
|---|---|
| Description | Seroconversion or significant increase as per CHMP criteria is defined as percentage of subjects with a pre vaccination HI titer <10 to a post vaccination titer ≥40 or a pre vaccination HI titer ≥10 and a ≥4-fold increase in post vaccination HI antibody titer. According to the CHMP criteria, the percentage of subjects achieving seroconversion or significant increase should be >40%. According to the CBER criteria, the lower bound of the two-sided 95% CI for the percentage of subjects achieving seroconversion/significant increase should be ≥40%. |
| Time Frame | Day 29 post vaccination |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed on the per-protocol dataset. |
| Arm/Group Title | Cohort 1 cTIV (9-17 Years) | Cohort 1 eTIV (9-17 Years) |
|---|---|---|
| Arm/Group Description | All subjects aged 9-17 years received one 0.5 mL injection, of Cell Culture-derived trivalent influenza vaccine. | All subjects aged 9-17 years received one 0.5 mL injection, of egg-derived trivalent influenza vaccine. |
| Measure Participants | 142 | 144 |
| Day 29 (A/H1N1) egg derived antigen assay |
77
|
77
|
| Day 29 (A/H3N2) egg derived antigen assay |
56
|
77
|
| Day 29 (B) egg derived antigen assay |
56
|
71
|
| Day29(A/H1N1)cell derived antigen assay(N=141,144) |
74
|
74
|
| Day29(A/H3N2)cell derived antigen assay(N=141,144) |
52
|
78
|
| Day29(B)cell derived antigen assay (N=141,144) |
63
|
69
|
| Title | Geometric Mean Titers After Two Doses of the Cell Derived or the Egg Derived Vaccine in 3 to 8 Year-old Children |
|---|---|
| Description | To evaluate immunogenicity in terms of Geometric Mean Titers (GMTs) in children 3 to 8 years of age after two doses of either cTIV vaccine or eTIV,administered 4 weeks apart. |
| Time Frame | Day 29 and Day 50 post vaccination |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed on the per-protocol dataset. |
| Arm/Group Title | Cohort 3 cTIV (3-8 Years) | Cohort 3 eTIV (3-8 Years) |
|---|---|---|
| Arm/Group Description | All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart, of Cell Culture-derived trivalent influenza vaccine. | All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart of egg-derived trivalent influenza vaccine. |
| Measure Participants | 524 | 513 |
| Baseline (A/H1N1) egg derived antigen assay |
16
|
15
|
| Day29(A/H1N1)egg derived antigen assay(N=515,507) |
152
|
157
|
| Day50(A/H1N1)egg derived antigen assay |
407
|
477
|
| Baseline (A/H3N2) egg derived antigen assay |
68
|
74
|
| Day29(A/H3N2)egg derived antigen assay(N=515,507) |
584
|
1075
|
| Day50(A/H3N2)egg derived antigen assay |
768
|
1293
|
| Baseline (B) egg derived antigen assay |
6.16
|
6.24
|
| Day29(B) egg derived antigen assay (N=515,507) |
19
|
27
|
| Day 50 (B) egg derived antigen assay |
25
|
44
|
| Baseline (A/H1N1) cell derived antigen assay |
19
|
17
|
| Day 29 (A/H1N1) cell derived antigen assay |
234
|
192
|
| Day50(A/H1N1)cell derived antigen assay(N=522,513) |
563
|
610
|
| Baseline (A/H3N2) cell derived antigen assay |
75
|
85
|
| Day 29 (A/H3N2) cell derived antigen assay |
653
|
1099
|
| Day50(A/H3N2)cell derived antigen assay(N=522,513) |
858
|
1329
|
| Baseline (B) cell derived antigen assay |
8.22
|
8.72
|
| Day 29 (B) cell derived antigen assay |
29
|
36
|
| Day50 (B) cell derived antigen assay(N=522,513) |
53
|
62
|
| Title | Geometric Mean Ratio After Two Doses of the Cell-derived or the Egg-derived Vaccine in 3 to 8 Year-old Children |
|---|---|
| Description | To evaluate immunogenicity in terms of Geometric Mean Ratio (GMR) in children 3 to 8 years of age after two doses of either the cTIV vaccine or the eTIV vaccine, administered 4 weeks apart according to the CHMP criteria. The criterion is met according to the European (CHMP) guideline if the mean geometric increase (GMR day 29/day 1 and GMR day 50/day 1) in HI antibody titer is >2.5 |
| Time Frame | Day 29 and Day 50 post vaccination |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed on the per-protocol dataset. |
| Arm/Group Title | Cohort 3 cTIV (3-8 Years) | Cohort 3 eTIV (3-8 Years) |
|---|---|---|
| Arm/Group Description | All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart, of Cell Culture-derived trivalent influenza vaccine. | All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart of egg-derived trivalent influenza vaccine. |
| Measure Participants | 524 | 513 |
| Day29 (A/H1N1)egg derived antigen assay(N=515,507) |
9.58
|
11
|
| Day 50 (A/H1N1) egg derived antigen assay |
25
|
33
|
| Day29 (A/H3N2)egg derived antigen assay(N=515,507) |
8.65
|
15
|
| Day 50 (A/H3N2) egg derived antigen assay |
11
|
17
|
| Day 29 (B) egg derived assay (N=515,507 |
3.04
|
4.36
|
| Day 50 (B) egg derived antigen assay |
3.99
|
7.04
|
| Day 29 (A/H1N1) cell derived antigen assay |
13
|
12
|
| Day50(A/H1N1)cell derived antigen assay(N=522,513 |
30
|
37
|
| Day 29 (A/H3N2) cell derived antigen assay |
8.73
|
13
|
| Day50(A/H3N2)cell derived antigen assay(N=522,513) |
12
|
16
|
| Day 29 (B) cell derived antigen assay |
3.59
|
4.14
|
| Day 50 (B) cell derived antigen assay(N=522,513) |
6.5
|
7.06
|
| Title | Percentages of Subjects Who Achieved HI Titers ≥40 After Two Doses of the Cell Culture Derived or the Egg Derived Influenza Vaccine in 3 to 8 Year-old Children |
|---|---|
| Description | To evaluate immunogenicity in terms of HI titers ≥40, in children 3-8 years of age after two doses of either cTIV vaccine or eTIV vaccine, administered 4 weeks apart. The criterion is met according to European (CHMP) guideline if the percentage of subjects achieving HI titers ≥40 is >70% and according to the US (CBER) guideline if the lower bound of the two sided 95%CI for percentage of subjects achieving HI titers ≥40 is ≥70%. |
| Time Frame | Day 29 and Day 50 post vaccination |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed on the per-protocol dataset. |
| Arm/Group Title | Cohort 3 cTIV (3-8 Years) | Cohort 3 eTIV (3-8 Years) |
|---|---|---|
| Arm/Group Description | All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart, of Cell Culture-derived trivalent influenza vaccine. | All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart of egg-derived trivalent influenza vaccine. |
| Measure Participants | 524 | 513 |
| Prevaccination (A/H1N1) egg derived antigen assay |
35
|
31
|
| Day29(A/H1N1)egg derived antigen assay (N=515,507) |
72
|
68
|
| Day 50 (A/H1N1) egg derived antigen assay |
96
|
97
|
| Prevaccination (A/H3N2) egg derived antigen assay |
67
|
70
|
| Day29(A/H3N2)egg derived antigen assay(N=515,507) |
87
|
85
|
| Day50 (A/H3N2) egg derived antigen assay |
96
|
94
|
| Prevaccination (B) egg derived antigen assay |
4
|
4
|
| Day 29 (B) egg derived antigen assay (N=515,507) |
35
|
40
|
| Day 50 (B) egg derived antigen assay |
40
|
55
|
| Prevaccination (A/H1N1) cell derived antigen assay |
36
|
33
|
| Day 29 (A/H1N1) cell derived antigen assay |
82
|
76
|
| Day50(A/H1N1)cell derived antigen assay(N=522,513) |
98
|
98
|
| Prevaccination (A/H3N2) cell derived antigen assay |
71
|
75
|
| Day 29 (A/H3N2) cell derived antigen assay |
89
|
85
|
| Day50(A/H3N2)cell derived antigen assay(N=522,513) |
98
|
93
|
| Prevaccination (B) cell derived antigen assay |
11
|
12
|
| Day 29 (B) cell derived antigen assay |
43
|
45
|
| Day 50 (B) cell derived antigen assay (N=522,513) |
60
|
62
|
| Title | Percentages of Subjects Who Achieved Seroconversion or Significant Increase in HI Titers After Two Doses of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 3 to 8 Year-old Children |
|---|---|
| Description | Seroconversion or significant increase as per CHMP criteria is defined as percentage of subjects with a pre vaccination HI titer <10 to a post vaccination titer ≥40 or a pre vaccination HI titer ≥10 and a ≥4-fold increase in post vaccination HI antibody titer. According to the CHMP criteria, the percentage of subjects achieving seroconversion or significant increase should be >40%. According to the CBER criteria, the lower bound of the two-sided 95% CI for the percentage of subjects achieving seroconversion/significant increase should be ≥40%. |
| Time Frame | Day 29 and Day 50 post vaccination |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed on the per-protocol dataset. |
| Arm/Group Title | Cohort 3 cTIV (3-8 Years) | Cohort 3 eTIV (3-8 Years) |
|---|---|---|
| Arm/Group Description | All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart, of Cell Culture-derived trivalent influenza vaccine. | All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart of egg-derived trivalent influenza vaccine. |
| Measure Participants | 524 | 513 |
| Day29(A/H1N1) egg derived antigen assay(N=515,507) |
70
|
67
|
| Day 50 (H1N1) egg derived antigen assay |
94
|
96
|
| Day29(A/H3N2) egg derived antigen assay(N=515,507) |
65
|
78
|
| Day 50 (A/H3N2) egg derived antigen assay |
77
|
86
|
| Day29(B) egg derived antigen assay(N=515,507) |
33
|
38
|
| Day 50 (B) egg derived antigen assay |
38
|
53
|
| Day 29 (A/H1N1) cell derived antigen assay |
79
|
75
|
| Day50(A/H1N1)cell derived antigen assay(N=522,513) |
96
|
96
|
| Day 29 (A/H3N2) cell derived antigen assay |
70
|
76
|
| Day50(A/H3N2)cell derived antigen assay(N=522,513) |
80
|
85
|
| Day 29 (B) cell derived antigen assay |
40
|
41
|
| Day 50(B)cell derived antigen assay(N=522,513) |
58
|
58
|
| Title | Number of Subjects Reporting Local and Systemic Reactions After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents. |
|---|---|
| Description | To evaluate safety and tolerability in terms of number of 9 to 17 year-old children and adolescents (cohorts 1 and 2) reporting local and systemic reactions following of one injection of the cTIV or the eTIV vaccine . |
| Time Frame | up to 7 days after vaccination |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed on the safety dataset |
| Arm/Group Title | Cohort 1+2 cTIV (9-17 Years) | Cohort 1+2 eTIV (9-17 Years) |
|---|---|---|
| Arm/Group Description | All subjects aged 9-17 years received one 0.5 mL injection, of Cell Culture-derived trivalent influenza vaccine. | All subjects aged 9-17 years received one 0.5 mL injection, of egg -derived trivalent influenza vaccine. |
| Measure Participants | 652 | 316 |
| Any Local |
276
|
141
|
| Injection site pain |
220
|
120
|
| Injection site erythema |
91
|
45
|
| Injection site induration |
44
|
28
|
| Injection site ecchymosis |
34
|
10
|
| Injection site swelling |
32
|
17
|
| Any Systemic |
188
|
95
|
| Chills |
26
|
13
|
| Malaise |
60
|
34
|
| Myalgia |
99
|
59
|
| Arthralgia |
27
|
17
|
| Headache |
92
|
44
|
| Sweating |
14
|
3
|
| Fatigue |
57
|
41
|
| Fever (≥38C) (N=651,316) |
5
|
3
|
| Any Other |
44
|
37
|
| Stayed at home (n=649,316) |
9
|
10
|
| Analgesic Medication Used |
42
|
31
|
| Title | Number of Subjects Reporting Local and Systemic Reactions After One and Two Doses of the Cell Culture-derived Vaccine or Egg-derived Influenza Vaccine in 3 to 8 Year-old Children. |
|---|---|
| Description | To evaluate the safety and tolerability of the cTIV and the eTIV influenza vaccines in 3 to 8 year-old children terms of number of participants reporting local and systemic reactions after each vaccination. |
| Time Frame | up to 7 days after each vaccination |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed on the safety dataset set. |
| Arm/Group Title | Cohort 3 cTIV (3-8 Years) | Cohort 3 eTIV (3-8 Years) |
|---|---|---|
| Arm/Group Description | All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart, of Cell Culture-derived trivalent influenza vaccine. | All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart of egg- derived trivalent influenza vaccine. |
| Measure Participants | 1599 | 1013 |
| Injection site pain |
653
|
398
|
| Injection site erythema |
337
|
206
|
| Injection site induration |
141
|
84
|
| Injection site ecchymosis |
144
|
99
|
| Injection site swelling |
119
|
85
|
| Chills |
70
|
68
|
| Malaise |
156
|
117
|
| Myalgia |
202
|
119
|
| Arthralgia |
65
|
28
|
| Headache |
182
|
144
|
| Sweating |
47
|
28
|
| Fatigue |
210
|
170
|
| Fever (≥ 38C) |
75
|
60
|
| Oral temp; 38 to <38.9 C (N=1598,1013) |
48
|
43
|
| Stayed at home (N=1582,1003,1519, 955) |
77
|
63
|
| Analgesic Medication Used |
221
|
148
|
| Oral temp; 39 to < 40 C (N=1598,1013) |
16
|
15
|
| Oral temp; ≥ 40 C (N=1598,1013) |
6
|
1
|
Adverse Events
| Time Frame | Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Solicited AEs - day 1 through day 7 after vaccination. All AEs- day 1 through day 29 ( cohort 1&2); day 1 through day 50 (cohort 3). SAEs, onset of chronic illness, and AEs that lead to withdrawal from the study and associated concomitant medications-day 29 to day 181 (cohort 1&2); day 50 through day 209 (cohort 3) | |||||||||||
| Arm/Group Title | Cohort 1+2 cTIV (9-17 Years) | Cohort 1+2 eTIV (9-17 Years) | Cohort 3 cTIV (3-8 Yrs; 1st Vaccination) | Cohort 3 eTIV (3-8 Yrs; 1st Vaccination) | Cohort 3 cTIV (3-8 Yrs; 2nd Vaccination) | Cohort 3 eTIV (3-8 Yrs; 2nd Vaccination) | ||||||
| Arm/Group Description | All subjects aged 9-17 years received one 0.5 mL injection, of Cell Culture-derived trivalent influenza vaccine. | All subjects aged 9-17 years received one 0.5 mL injection, of egg -derived trivalent influenza vaccine. | All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart, of Cell Culture-derived trivalent influenza vaccine. | All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart of egg-derived trivalent influenza vaccine. | All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart, of Cell Culture-derived trivalent influenza vaccine. | All subjects aged 3-8 years received two 0.5 mL injections, administered four weeks apart of egg-derived trivalent influenza vaccine. | ||||||
All Cause Mortality |
||||||||||||
| Cohort 1+2 cTIV (9-17 Years) | Cohort 1+2 eTIV (9-17 Years) | Cohort 3 cTIV (3-8 Yrs; 1st Vaccination) | Cohort 3 eTIV (3-8 Yrs; 1st Vaccination) | Cohort 3 cTIV (3-8 Yrs; 2nd Vaccination) | Cohort 3 eTIV (3-8 Yrs; 2nd Vaccination) | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||
Serious Adverse Events |
||||||||||||
| Cohort 1+2 cTIV (9-17 Years) | Cohort 1+2 eTIV (9-17 Years) | Cohort 3 cTIV (3-8 Yrs; 1st Vaccination) | Cohort 3 eTIV (3-8 Yrs; 1st Vaccination) | Cohort 3 cTIV (3-8 Yrs; 2nd Vaccination) | Cohort 3 eTIV (3-8 Yrs; 2nd Vaccination) | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/652 (0.8%) | 3/316 (0.9%) | 2/1599 (0.1%) | 0/1013 (0%) | 7/1557 (0.4%) | 5/977 (0.5%) | ||||||
| Congenital, familial and genetic disorders | ||||||||||||
| Thalassemia beta | 0/652 (0%) | 0 | 0/316 (0%) | 0 | 0/1599 (0%) | 0 | 0/1013 (0%) | 0 | 1/1557 (0.1%) | 1 | 0/977 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||
| Abdominal pain | 1/652 (0.2%) | 1 | 0/316 (0%) | 0 | 0/1599 (0%) | 0 | 0/1013 (0%) | 0 | 0/1557 (0%) | 0 | 0/977 (0%) | 0 |
| Appendix disorder | 1/652 (0.2%) | 1 | 0/316 (0%) | 0 | 0/1599 (0%) | 0 | 0/1013 (0%) | 0 | 0/1557 (0%) | 0 | 0/977 (0%) | 0 |
| Infections and infestations | ||||||||||||
| Abscess limb | 0/652 (0%) | 0 | 0/316 (0%) | 0 | 0/1599 (0%) | 0 | 0/1013 (0%) | 0 | 0/1557 (0%) | 0 | 1/977 (0.1%) | 1 |
| Gastroentritis | 0/652 (0%) | 0 | 0/316 (0%) | 0 | 0/1599 (0%) | 0 | 0/1013 (0%) | 0 | 1/1557 (0.1%) | 1 | 1/977 (0.1%) | 1 |
| Infectious mononucleosis | 0/652 (0%) | 0 | 0/316 (0%) | 0 | 1/1599 (0.1%) | 1 | 0/1013 (0%) | 0 | 0/1557 (0%) | 0 | 0/977 (0%) | 0 |
| Influenza | 0/652 (0%) | 0 | 1/316 (0.3%) | 1 | 0/1599 (0%) | 0 | 0/1013 (0%) | 0 | 0/1557 (0%) | 0 | 0/977 (0%) | 0 |
| Otitis media chronic | 0/652 (0%) | 0 | 0/316 (0%) | 0 | 0/1599 (0%) | 0 | 0/1013 (0%) | 0 | 0/1557 (0%) | 0 | 1/977 (0.1%) | 1 |
| Pelvic abscess | 1/652 (0.2%) | 1 | 0/316 (0%) | 0 | 0/1599 (0%) | 0 | 0/1013 (0%) | 0 | 0/1557 (0%) | 0 | 0/977 (0%) | 0 |
| Pharyngotonsillitis | 0/652 (0%) | 0 | 0/316 (0%) | 0 | 0/1599 (0%) | 0 | 0/1013 (0%) | 0 | 1/1557 (0.1%) | 1 | 0/977 (0%) | 0 |
| Pneumonia bacterial | 0/652 (0%) | 0 | 1/316 (0.3%) | 1 | 0/1599 (0%) | 0 | 0/1013 (0%) | 0 | 0/1557 (0%) | 0 | 0/977 (0%) | 0 |
| Respiratory tract infection viral | 0/652 (0%) | 0 | 0/316 (0%) | 0 | 0/1599 (0%) | 0 | 0/1013 (0%) | 0 | 1/1557 (0.1%) | 1 | 0/977 (0%) | 0 |
| Streptococcal bacteraemia | 0/652 (0%) | 0 | 1/316 (0.3%) | 1 | 0/1599 (0%) | 0 | 0/1013 (0%) | 0 | 0/1557 (0%) | 0 | 0/977 (0%) | 0 |
| Viral infection | 1/652 (0.2%) | 1 | 0/316 (0%) | 0 | 0/1599 (0%) | 0 | 0/1013 (0%) | 0 | 0/1557 (0%) | 0 | 0/977 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||
| Concussion | 0/652 (0%) | 0 | 0/316 (0%) | 0 | 0/1599 (0%) | 0 | 0/1013 (0%) | 0 | 2/1557 (0.1%) | 2 | 0/977 (0%) | 0 |
| Contusion | 0/652 (0%) | 0 | 0/316 (0%) | 0 | 1/1599 (0.1%) | 1 | 0/1013 (0%) | 0 | 1/1557 (0.1%) | 1 | 0/977 (0%) | 0 |
| Eye injury | 0/652 (0%) | 0 | 0/316 (0%) | 0 | 0/1599 (0%) | 0 | 0/1013 (0%) | 0 | 1/1557 (0.1%) | 1 | 0/977 (0%) | 0 |
| Investigations | ||||||||||||
| Body height below normal | 1/652 (0.2%) | 1 | 0/316 (0%) | 0 | 0/1599 (0%) | 0 | 0/1013 (0%) | 0 | 0/1557 (0%) | 0 | 0/977 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||
| Dehydration | 1/652 (0.2%) | 1 | 0/316 (0%) | 0 | 0/1599 (0%) | 0 | 0/1013 (0%) | 0 | 0/1557 (0%) | 0 | 0/977 (0%) | 0 |
| Diabetes mellitus | 0/652 (0%) | 0 | 0/316 (0%) | 0 | 0/1599 (0%) | 0 | 0/1013 (0%) | 0 | 1/1557 (0.1%) | 1 | 0/977 (0%) | 0 |
| Nervous system disorders | ||||||||||||
| Post procedural haemorrhage | 0/652 (0%) | 0 | 0/316 (0%) | 0 | 0/1599 (0%) | 0 | 0/1013 (0%) | 0 | 0/1557 (0%) | 0 | 1/977 (0.1%) | 1 |
| Psychiatric disorders | ||||||||||||
| Major depression | 1/652 (0.2%) | 1 | 0/316 (0%) | 0 | 0/1599 (0%) | 0 | 0/1013 (0%) | 0 | 0/1557 (0%) | 0 | 0/977 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||||
| Ovarian torsion | 0/652 (0%) | 0 | 1/316 (0.3%) | 1 | 0/1599 (0%) | 0 | 0/1013 (0%) | 0 | 0/1557 (0%) | 0 | 0/977 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| Bronchitis chronic | 0/652 (0%) | 0 | 0/316 (0%) | 0 | 0/1599 (0%) | 0 | 0/1013 (0%) | 0 | 0/1557 (0%) | 0 | 1/977 (0.1%) | 1 |
| Surgical and medical procedures | ||||||||||||
| Tonsillectomy | 0/652 (0%) | 0 | 0/316 (0%) | 0 | 0/1599 (0%) | 0 | 0/1013 (0%) | 0 | 0/1557 (0%) | 0 | 1/977 (0.1%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||||||||
| Cohort 1+2 cTIV (9-17 Years) | Cohort 1+2 eTIV (9-17 Years) | Cohort 3 cTIV (3-8 Yrs; 1st Vaccination) | Cohort 3 eTIV (3-8 Yrs; 1st Vaccination) | Cohort 3 cTIV (3-8 Yrs; 2nd Vaccination) | Cohort 3 eTIV (3-8 Yrs; 2nd Vaccination) | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 328/652 (50.3%) | 168/316 (53.2%) | 799/1599 (50%) | 507/1013 (50%) | 670/1557 (43%) | 413/977 (42.3%) | ||||||
| General disorders | ||||||||||||
| Fatigue | 57/652 (8.7%) | 67 | 41/316 (13%) | 47 | 155/1599 (9.7%) | 171 | 119/1013 (11.7%) | 143 | 99/1557 (6.4%) | 110 | 82/977 (8.4%) | 92 |
| Injection site erythema | 91/652 (14%) | 94 | 45/316 (14.2%) | 45 | 197/1599 (12.3%) | 198 | 138/1013 (13.6%) | 139 | 209/1557 (13.4%) | 211 | 118/977 (12.1%) | 121 |
| Injection site induration | 44/652 (6.7%) | 44 | 28/316 (8.9%) | 29 | 87/1599 (5.4%) | 89 | 44/1013 (4.3%) | 45 | 66/1557 (4.2%) | 66 | 51/977 (5.2%) | 51 |
| Injection site pain | 220/652 (33.7%) | 227 | 120/316 (38%) | 122 | 451/1599 (28.2%) | 462 | 251/1013 (24.8%) | 261 | 421/1557 (27%) | 430 | 266/977 (27.2%) | 278 |
| Injection site haemorrhage | 34/652 (5.2%) | 37 | 10/316 (3.2%) | 11 | 98/1599 (6.1%) | 106 | 60/1013 (5.9%) | 67 | 52/1557 (3.3%) | 58 | 43/977 (4.4%) | 51 |
| Malaise | 60/652 (9.2%) | 68 | 34/316 (10.8%) | 41 | 103/1599 (6.4%) | 118 | 78/1013 (7.7%) | 85 | 76/1557 (4.9%) | 86 | 50/977 (5.1%) | 56 |
| Pyrexia | 12/652 (1.8%) | 13 | 5/316 (1.6%) | 7 | 88/1599 (5.5%) | 96 | 73/1013 (7.2%) | 84 | 63/1557 (4%) | 70 | 44/977 (4.5%) | 49 |
| Musculoskeletal and connective tissue disorders | ||||||||||||
| Myalgia | 99/652 (15.2%) | 107 | 59/316 (18.7%) | 67 | 141/1599 (8.8%) | 150 | 76/1013 (7.5%) | 88 | 100/1557 (6.4%) | 103 | 67/977 (6.9%) | 70 |
| Nervous system disorders | ||||||||||||
| Headache | 99/652 (15.2%) | 125 | 47/316 (14.9%) | 56 | 143/1599 (8.9%) | 167 | 111/1013 (11%) | 135 | 94/1557 (6%) | 110 | 73/977 (7.5%) | 89 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| Cough | 10/652 (1.5%) | 10 | 4/316 (1.3%) | 4 | 124/1599 (7.8%) | 130 | 75/1013 (7.4%) | 87 | 70/1557 (4.5%) | 75 | 51/977 (5.2%) | 52 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Posting Director |
|---|---|
| Organization | Novartis Vaccines and Diagnostics |
| Phone | |
| RegistryContactVaccinesUS@novartis.com |
Responsible Party:
Novartis
ClinicalTrials.gov Identifier:
NCT00645411
Other Study ID Numbers:
- V58P12
- Eudract Number: 2007-001534-13
First Posted:
Mar 27, 2008
Last Update Posted:
Nov 23, 2015
Last Verified:
Oct 1, 2015