Pediatric Safety and Immunogenicity Study of Cell-Culture Derived and Egg-based Subunit Influenza Vaccines in Healthy Children and Adolescents
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
研究概览
地位
条件
研究类型
注册 (实际的)
阶段
- 阶段2
- 第三阶段
联系人和位置
学习地点
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Dakovo、克罗地亚
- Site 44:Spec. Pediatric Dispensary
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Ljudevita Gaja 2, Djakovo、克罗地亚
- Site 83
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Sisak、克罗地亚
- Site 43: Spec. Pediatric Dispensary
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Zagreb、克罗地亚
- Site 27:Institute of Public Health
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Zagreb、克罗地亚
- Site 29: Institute of Public Health
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Zagreb、克罗地亚
- Site 40:Spec. Pediatric Dispensary
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Zagreb、克罗地亚
- Site 49: Spec. Pediatric Dispensary
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Zagreb、克罗地亚
- Site 50: Spec. Pediatric Dispensary
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Zagreb、克罗地亚
- Site 86: Spec. Pediatric Dispensary
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Budapest、匈牙利、1042
- Site 57: Házi Gyermekorvosi Rendelő
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Budapest、匈牙利、1089
- Site 53: Heim Pál Gyermekkórház
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Budapest、匈牙利、1097
- Site 52: Ferencvárosi Gyermekorvos Kft.
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Budapest、匈牙利、1136
- Site 56: Házi Gyermekorvosi Rendelő
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Budapest、匈牙利、1173
- Site 54: Házi Gyermekorvosi Rendelő
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Miskolc、匈牙利、3534
- Site 51: 5053. számú Gyermekorvosi Rendelő
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Nyíregyháza、匈牙利、4481
- Site 55: Revamed kft.
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Szombathely、匈牙利、9700
- Site 59: Vas Megyei Markusovszky Lajos, Általános, Rehabilitációs és Gyógyfürdő Kórház, Egyetemi Oktató Kórház
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Ferrara、意大利、44100
- Site 42: Dipartimento di Medicina Clinica e Sperimentale - Sezione di Igiene e Medicina Preventiva
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Genova、意大利、16132
- Site 47: Dipartimento Scienze della Salute, Sezione di Igiene e Medicina Preventiva, Univesità di Genova
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Novara、意大利、28100
- Site 41: Ospedale Maggiore della Carità-Clinica Pediatrica
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Perugia、意大利、06070
- 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)
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Ragusa、意大利、97100
- Site 45: AUSL 7
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Kaunas、立陶宛、48259
- Site 35
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Vilnius、立陶宛、01117
- Site 36
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Vilnius、立陶宛、02169
- Site 32
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Vilnius、立陶宛、04318
- Site 34
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Vilnius、立陶宛、10207
- Site 31
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Vilnius、立陶宛、11200
- Site 33
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Arges
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Campulung Muscel、Arges、罗马尼亚、115100
- Site 25
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Dolj
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Craiova、Dolj、罗马尼亚、200642
- Site 21
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Arkansas
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Fayetteville、Arkansas、美国、72703
- Site 09
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California
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Downey、California、美国、90241
- Site 10
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Kentucky
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Bardstown、Kentucky、美国、40004
- Site 02
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Louisiana
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Metairie、Louisiana、美国、70006
- Site 14
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Missouri
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St. Louis、Missouri、美国、63104
- Site 01
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Nebraska
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Omaha、Nebraska、美国、68134
- Site 11
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New Jersey
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Edison、New Jersey、美国、08817
- Site 04
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New York
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Endwell、New York、美国、13760
- Site 05
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Texas
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Fort Worth、Texas、美国、76135
- Site 16
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San Angelo、Texas、美国、76904
- Site 13
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San Antonio、Texas、美国、78205
- Site 12
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Utah
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Bountiful、Utah、美国、84010
- Site 08
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Salt Lake City、Utah、美国、84109
- Site 07
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Salt Lake City、Utah、美国、84121
- Site 03
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Virginia
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Burke、Virginia、美国、22105
- Site 06
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Washington
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Spokane、Washington、美国、99202
- Site 15
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Helsinki、芬兰、00100
- Site 71: Etelä-Helsingin rokotetutkimusklinikka
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Helsinki、芬兰、00930
- Site 72: Itä-Helsingin rokotetutkimusklinikka
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Järvenpää、芬兰、04400
- Site 76: Järvenpään rokotetutkimusklinikka
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Kotka、芬兰、48600
- Site 77: Kotkan rokotetutkimusklinikka
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Lahti、芬兰、15140
- Site 67: Lahden rokotetutkimusklinikka
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Oulu、芬兰、90100
- Site 75: Oulun rokotetutkimusklinikka
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Pori、芬兰、28120
- Site 68: Porin rokotetutkimusklinikka
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Tampere、芬兰、33100
- Site 66: Tampereen rokotetutkimusklinikka
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Turku、芬兰、20520
- Site 69: Turun rokotetutkimusklinikka
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Vantaa、芬兰、01300
- Site 73: Itä-Vantaan rokotetutkimusklinikka
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Vantaa、芬兰、01600
- Site 74: Länsi-Vantaan rokotetutkimusklinikka
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Espoo
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Heikintori、Espoo、芬兰、02100
- Site 70: Espoon rokotetutkimusklinikka
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Kokkola
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Rantakatu 7、Kokkola、芬兰、67100
- Site 79: Kokkola Vaccine Research Clinic
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Kuopio
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Microkatu 1,Osa/Section A, 3rd floor PL1188、Kuopio、芬兰、70211
- Site 78: Kuopio Vaccine Research Clinic
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
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.
学习计划
研究是如何设计的？
设计细节
- 主要用途：预防
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：单身的
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：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
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One 0.5 ml injection of the cell culture-derived influenza vaccine in the deltoid muscle, preferably of the nondominant arm.
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.
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有源比较器：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.
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One 0.5 ml injection of the conventional egg-derived influenza vaccine in the deltoid muscle, preferably of the nondominant arm.
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.
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实验性的：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
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One 0.5 ml injection of the cell culture-derived influenza vaccine in the deltoid muscle, preferably of the nondominant arm.
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.
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有源比较器：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
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One 0.5 ml injection of the conventional egg-derived influenza vaccine in the deltoid muscle, preferably of the nondominant arm.
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.
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Geometric Mean Titers of the Cell Culture-derived Vaccine Compared With the Egg-derived Vaccine in 3 to 8 Year-old Children
大体时间：Day 50 post vaccination
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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. |
Day 50 post vaccination
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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
大体时间：Day 50 post vaccination
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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. |
Day 50 post vaccination
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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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
大体时间：Day 29 post vaccination
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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. |
Day 29 post vaccination
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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.
大体时间：Day 29 post vaccination
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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. |
Day 29 post vaccination
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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
大体时间：Day 29 post vaccination
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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%. |
Day 29 post vaccination
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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
大体时间：Day 29 post vaccination
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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%. |
Day 29 post vaccination
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Geometric Mean Titers After Two Doses of the Cell Derived or the Egg Derived Vaccine in 3 to 8 Year-old Children
大体时间：Day 29 and Day 50 post vaccination
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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.
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Day 29 and Day 50 post vaccination
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Geometric Mean Ratio After Two Doses of the Cell-derived or the Egg-derived Vaccine in 3 to 8 Year-old Children
大体时间：Day 29 and Day 50 post vaccination
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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 |
Day 29 and Day 50 post vaccination
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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
大体时间：Day 29 and Day 50 post vaccination
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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%. |
Day 29 and Day 50 post vaccination
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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
大体时间：Day 29 and Day 50 post vaccination
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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%. |
Day 29 and Day 50 post vaccination
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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.
大体时间：up to 7 days after vaccination
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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 .
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up to 7 days after vaccination
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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.
大体时间：up to 7 days after each vaccination
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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.
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up to 7 days after each vaccination
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合作者和调查者
赞助
出版物和有用的链接
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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