A Phase III/IV, Stratified, Randomized, Observer Blind, Multicenter Clinical Study to Evaluate the Efficacy, Safety and Immunogenicity of a Cell-Based Quadrivalent Subunit Influenza Virus Vaccine Compared to Non-Influenza Comparator Vaccine in Subjects ≥2 to <18 Years of Age
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 4,514
- 试验地点
- 69
- 主要终点
- Primary Efficacy: First Occurrence of Either RT-PCR- or Culture-confirmed Influenza (Time-to-event Analyses) Due to Any Influenza Type A or B Strain Regardless of Antigenic Match to the Strains Selected for the Seasonal Vaccine in Subjects ≥2 to <18 Years
研究概览
简要总结
This Phase 3/4, randomized, observer-blind, multi-center study, stratified study evaluated the immune (antibody) response, efficacy and safety of a cell-derived quadrivalent subunit influenza virus vaccine (Seqirus QIVc) in comparison with a non-influenza comparator, meningococcal serogroup A, C, W-135, and Y (Menveo®, GlaxoSmithKline Biologicals, S.A.) in healthy pediatric subjects ≥2 Years to <18 Years of Age
详细描述
This Phase 3/4, randomized, observer-blind, multi-center, stratified study evaluated the efficacy, safety, and immunogenicity of a cell-derived quadrivalent subunit influenza virus vaccine (Seqirus QIVc) compared to a non-influenza comparator vaccine in healthy male and female participants between 2 to <18 years of age. A total of 4514 children/teens were randomized, receiving either QIVc or the non-influenza comparator vaccine. The comparator was (meningococcal [Groups A, C, W-135, and Y] oligosaccharide diphtheria CRM197 conjugate vaccine [Men ACWY]). Randomized enrollment was stratified in a 1:1 ratio via an Interactive Response Technology (IRT) system which assigned the participants into two age cohorts: 2 to <9 years of age and 9 to <18 years of age. Subjects between 2 to <9 years of age were further stratified by previous influenza vaccine status ("previously vaccinated" or "not previously vaccinated").
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female ≥2 to <18 years of age on the day of the first study vaccination
- •Subject's parent(s) or legal guardian(s) who was/were able to give informed consent/dissent after the nature of the study had been explained in accordance with the practices described in the study and according to local regulatory requirements
- •If the subject was of an age where, according to local regulations, informed assent was required, he/she must have provided assent to participate in the study
- •Subject/subject's parent(s) or legal guardian(s) was/were able to comply with study procedures and was/were available for follow-up; and
- •Subject was in generally good health as per the investigator's medical judgment
排除标准
- •Clinical signs of fever and/or an oral temperature of ≥100.4°F (38.0°C) within 3 days prior to vaccination;
- •A known history of any anaphylaxis, serious vaccine reactions or hypersensitivity to any of the vaccine components described in the Investigator's Brochure, or had any of the contraindications listed in the package insert of the comparator vaccine;
- •A history of Guillain-Barré syndrome or other de-myelinating diseases such as encephalomyelitis and transverse myelitis;
- •Female subject of childbearing potential (ie, post onset of menarche and before natural or induced menopause), sexually active, and who did not use any acceptable contraceptive methods for at least 2 months prior to study entry and who did not intend to use any acceptable contraceptive methods throughout subject participation (acceptable contraceptive methods included: abstinence; hormonal contraceptive [such as oral, injection, transdermal patch, implant]; diaphragm with spermicide; tubal occlusion device; intrauterine device [IUD]; tubal ligation; male partner using condom; or male partner having been vasectomized);
- •Pregnant or breast feeding female;
- •Subject and/or subject's parent/guardians who were not able to comprehend or follow all required study procedures for the entire period of the study;
- •Received prior Meningococcal ACWY vaccination that conflicted with national recommendations or local practices for the timing of the primary or the booster vaccination;
- •Received influenza vaccination or had documented influenza disease in the last 6 months;
- •Known or suspected congenital or acquired immunodeficiency; or received immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or systemic corticosteroid therapy (prednisone or equivalent) at any dose for more than 2 consecutive weeks (14 days) within the past 3 months. Topical, inhaled and intra-nasal corticosteroids were permitted. Intermittent use (1 dose in 30 days) of intra-articular corticosteroids was also permitted;
- •Administration of immunoglobulin and/or any blood products within the 3 months preceding vaccination, or administration was planned during the study;
- •Participated in any clinical study with another investigational product within 30 days prior to first study visit or intended to participate in another clinical study at any time during the conduct of this study. Concomitant participation in an observational study (not involving drugs, vaccines, or medical devices) was acceptable;
- •Medical conditions or treatments contraindicating IM vaccination due to increased risk of bleeding. These included known bleeding disorders (such as thrombocytopenia), or treatment with anticoagulants (such as warfarin) in the 3 weeks preceding vaccination. Antiplatelet agents such as low-dose aspirin, ticlopidine (Ticlid) and clopidogrel (Plavix) were permitted;
- •Evidence or history (within the previous 12 months) of drug or alcohol abuse;
- •Study personnel or immediate family members (brother, sister, child, parent), the spouse of study personnel or individuals who were financially or emotionally dependent on study staff;
- •Participated in this study in a prior season, if applicable; or
- •Any clinical condition that, in the opinion of the investigator, may have interfered with the results of the study or pose additional risk to the subject due to participation in the study.
结局指标
主要结局
Primary Efficacy: First Occurrence of Either RT-PCR- or Culture-confirmed Influenza (Time-to-event Analyses) Due to Any Influenza Type A or B Strain Regardless of Antigenic Match to the Strains Selected for the Seasonal Vaccine in Subjects ≥2 to <18 Years
时间窗: Day 14 to Day 180 or until the end of the influenza season, whichever is longer
The primary efficacy endpoint was defined as the time from the last study vaccination to the onset of the first occurrence of either RT-PCR- or culture-confirmed influenza (time-to-event analyses) due to any influenza Type A or B strain regardless of antigenic match to the strains selected for the seasonal vaccine, that occurred more than 14 days after the last vaccination until the end of the influenza season. Dataset Used: FAS-Efficacy = All subjects in the All Enrolled Set who received at least one dose of study vaccine and were evaluated for efficacy from 14 days after the last vaccination. The success criterion used for this primary objective was as follows: The efficacy of the QIVc was demonstrated if the lower limit (LL) of the 2-sided 95% confidence interval (CI) for VE was above 20%.
Co-Primary: First Occurrence of Either RT-PCR- or Culture-confirmed Influenza (Time-to-event Analyses) Due to Any Influenza Type A or B Strain Regardless of Antigenic Match to the Strains Selected for the Seasonal Vaccine in Subjects ≥3 to <18 Years
时间窗: Day 14 to Day 180 or until the end of the influenza season, whichever is longer
The co-primary efficacy endpoint: was defined as the time from the last study vaccination to the onset of the first occurrence of either RT-PCR- or culture-confirmed influenza (time-to-event analyses) due to any influenza Type A or B strain regardless of antigenic match to the strains selected for the seasonal vaccine, that occurred more than 14 days after the last vaccination until the end of the influenza season.Absolute vaccine efficacy of QIVc by first occurrence RT-PCR or culture confirmed influenza, due to any influenza Type A and B strain in subjects ≥3 years to \<18 years of age
次要结局
- Secondary Efficacy #3: First Occurrence of Culture-confirmed Influenza Due to Any Influenza Type A or B Strain Regardless of Antigenic Match to the Strains Selected for the Seasonal Vaccine(Day 14 to Day 180 or until the end of the influenza season, whichever is longer.)
- ISecondary Immunogenicity: Percentage of Subjects Achieving Seroconversion for 4 Influenza Strains (HI Assay)(Day 22 (all previously vaccinated subjects) or Day 29 and Day 50 (all not previously vaccinated subjects))
- Secondary Efficacy #1: First Occurrence of Either RT-PCR- or Culture-confirmed Influenza Due to Any Influenza Type A or B Strain Regardless of Antigenic Match to the Strains Selected for the Seasonal Vaccine(Day 14 to Day 180 or until the end of the influenza season, whichever is longer.)
- Secondary Efficacy #2: First Occurrence of RT-PCR-confirmed Influenza Due to Any Influenza Type A or B Strain Regardless of Antigenic Match to the Strains Selected for the Seasonal Vaccine(Day 14 to Day 180 or until the end of the influenza season, whichever is longer.)
- Secondary Efficacy #4: First Occurrence of Culture-confirmed Influenza Due to Influenza Type A or B Strain Antigenically Matched to the Strains Selected for the Seasonal Vaccine(Day 14 to Day 180 or until the end of the influenza season, whichever is longer.)
- Secondary Immunogenicity: Geometric Mean Ratio for 4 Influenza Strains (HI Assay)(Day 22/Day 1 (all previously vaccinated subjects) or Day 29/Day 1 and Day 50/Day 1 (all not previously vaccinated subjects receiving 2 doses))
- Secondary Immunogenicity: Percentage of Subjects With HI Titer ≥1:40 for All 4 Influenza Strains (HI Assay)(Day 1 (all subjects), Day 22 (all "previously vaccinated" subjects receiving a single vaccine dose) or Days 29 and 50 (all "not previously vaccinated"subjects receiving 2 doses))
- Secondary Immunogenicity: Geometric Mean Titers for 4 Influenza Strains (HI Assay)(Day 1 (all subjects), Day 22 (all previously vaccinated subjects) or Day 29 and Day 50 (all not previously vaccinated subjects receiving 2 doses))
- Safety: Percentage of Subjects With Solicited Local and Systemic Adverse Events for 7 Days After Vaccination(days after vaccination on Day 1 (for "previously vaccinated" subjects) or for 7 days after vaccination on Day 1 and Day 29 (for "not previously vaccinated" subjects))
- Safety: Percentage of Subjects With Unsolicited AEs for 21 Days After Vaccination(Day 1 to Day 22 (for previously vaccinated subjects) or Day 1 to Day 50 (for not previously vaccinated subjects))
- Safety: Subjects With SAEs, AEs Leading to Withdrawal From Vaccination and/or the Study,(MAAEs) Within 30 Days of a 1st Occurrence, Post-ILI, and NOCDs Reported During Entire Study Participation or End of Flue Season, Whichever Was Longer(Day 1 to Day 181 (for previously vaccinated subjects) or to Day 209 (for not previously vaccinated subjects))