A Study to Evaluate the Safety and Immunogenicity of an A/California/7/2009 (H1N1)V-like Vaccine GSK2340274A or GSK2340273A Co-administered With Trivalent Inactivated Seasonal Influenza Vaccine in Adults 19 to 40 Years of Age
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 611
- 试验地点
- 8
- 主要终点
- Hemagglutination Inhibition (HI) Antibody Titers Against A/California/7/2009 H1N1 Vaccine Strain.
研究概览
简要总结
The purpose of this study is to characterize the safety and immunogenicity of the H1N1 (swine) flu vaccines GSK2340274A and GSK2340273A when co-administered with the seasonal flu vaccine in adults 19 to 40 years of age.
详细描述
Collaborators: United States Department of Health and Human Services, Office of Biomedical Advanced Research and Development Authority
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 19 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subjects who the investigator believes can and will comply with the requirements of the protocol.
- •Written informed consent obtained from the subject.
- •Male or female adults, 19-40 years of age at the time of the first vaccination.
- •Safety laboratory tests results within the parameters specified in the protocol.
- •Satisfactory baseline medical assessment by physical examination.
- •Comprehension of the study requirements, ability to comprehend and comply with procedures for collection of safety data, expressed availability for the required study period, and ability and willingness to attend scheduled visits as documented by signature on the informed consent document.
- •Access to a consistent means of telephone contact, which may be either in the home or at the workplace, land line, or mobile, but NOT a pay phone or other multiple-user device.
- •Female subjects of non-childbearing potential may be enrolled in the study.
- •Female subjects of childbearing potential may be enrolled in the study, if the subject:
- •has practiced adequate contraception for 30 days prior to vaccination, and
- •has a negative pregnancy test on the day of first vaccination, and
- •has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series.
排除标准
- •Previous vaccination with an H1N1v-like virus vaccine or a medical history of physician-confirmed infection with an H1N1v-like virus.
- •Prior receipt at any time of any seasonal influenza vaccine.
- •Planned administration of any vaccine not foreseen by the study protocol between Day 0 and the Day 63 phlebotomy.
- •Administration of any licensed vaccine within 4 weeks before the first study vaccine dose.
- •Use of any investigational or non-registered product other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period.
- •Receipt of systemic glucocorticoids within one month prior to study enrolment, or any other cytotoxic or immunosuppressive drug within six months of study enrolment. Topical, intra-articularly injected, or inhaled glucocorticoids, topical calcineurin inhibitors or imiquimod are allowed.
- •Receipt of any immunoglobulins and/or any blood products within three months of study enrolment or planned administration of any of these products during the study period.
- •Presence of evidence of substance abuse or of neurological or psychiatric diagnoses which, even if stable, are deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports.
- •Presence of a temperature >= 38.0ºC (>=100.4ºF), or acute symptoms greater than "mild" severity on the scheduled date of first vaccination.
- •Diagnosed with cancer, or treatment for cancer, within 3 years.
- •Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
- •Any significant disorder of coagulation or treatment with warfarin derivatives or heparin. Persons receiving individual doses of low molecular weight heparin outside of 24 hours prior to vaccination are eligible. Persons receiving prophylactic antiplatelet medications, e.g., low-dose acetylsalicylic acid, and without a clinically-apparent bleeding tendency, are eligible.
- •An acute evolving neurological disorder or history of Guillain-Barré syndrome within six weeks of receipt of seasonal influenza vaccine.
- •Any known or suspected allergy to any constituent of influenza vaccines; a history of anaphylactic-type reaction to any constituent of influenza vaccines; or a history of severe adverse reaction to a previous influenza vaccine.
- •Known pregnancy or a positive urine beta-human chorionic gonadotropin test result prior to first vaccination.
- •Lactating or nursing women.
研究组 & 干预措施
Flulaval/placebo/unadjuvanted Arepanrix Group
subjects received co-administration of Flulaval vaccine and saline placebo on Day 0 followed by the unadjuvanted formulation of Arepanrix vaccine on Day 21 and Day 42. All vaccines were administered intramuscularly in the deltoids of the dominant or non dominant arm. At Day 0 the two vaccines were administered each in a separate arm, at Day 21 in the dominant arm and at Day 42 in the non-dominant arm.
干预措施: GSK2340273A (Biological)
Flulaval/placebo/Arepanrix Group
subjects received co-administration of Flulaval vaccine and saline placebo on Day 0 followed the administration of Arepanrix vaccine on Day 21 and Day 42. All vaccines were administered intramuscularly in the deltoids of the dominant or non dominant arm. At Day 0 the two vaccines were administered each in a separate arm, at Day 21 in the dominant arm and at Day 42 in the non-dominant arm.
干预措施: GSK2340274A (Biological)
Arepanrix/placebo/Flulaval Group
subjects received co-administration of Arepanrix vaccine and saline placebo on Day 0 followed by Arepanrix vaccine on Day 21 and Flulaval vaccine on Day 42. All vaccines were administered intramuscularly in the deltoids of the dominant or non dominant arm. At Day 0 the two vaccines were administered each in a separate arm, at Day 21 in the dominant arm and at Day 42 in the non-dominant arm.
干预措施: GSK2340274A (Biological)
Unadjuvanted Arepanrix/placebo/Flulaval Group
subjects received co-administration of the unadjuvanted formulation of Arepanrix vaccine and saline placebo on Day 0 followed by the unadjuvanted formulation of Arepanrix vaccine on Day 21 and Flulaval vaccine on Day 42. All vaccines were administered intramuscularly in the deltoids of the dominant or non dominant arm. At Day 0 the two vaccines were administered each in a separate arm, at Day 21 in the dominant arm and at Day 42 in the non-dominant arm.
干预措施: GSK2340273A (Biological)
Flulaval/Arepanrix/placebo Group
subjects received co-administration of Flulaval vaccine and Arepanrix vaccine on Day 0 followed by Arepanrix vaccine on Day 21 and saline placebo on Day 42. All vaccines were administered intramuscularly in the deltoids of the dominant or non dominant arm. At Day 0 the two vaccines were administered each in a separate arm, at Day 21 in the dominant arm and at Day 42 in the non-dominant arm.
干预措施: GSK2340274A (Biological)
Flulaval/placebo/unadjuvanted Arepanrix Group
subjects received co-administration of Flulaval vaccine and saline placebo on Day 0 followed by the unadjuvanted formulation of Arepanrix vaccine on Day 21 and Day 42. All vaccines were administered intramuscularly in the deltoids of the dominant or non dominant arm. At Day 0 the two vaccines were administered each in a separate arm, at Day 21 in the dominant arm and at Day 42 in the non-dominant arm.
干预措施: Seasonal trivalent influenza vaccine (TIV) (Biological)
Flulaval/placebo/unadjuvanted Arepanrix Group
subjects received co-administration of Flulaval vaccine and saline placebo on Day 0 followed by the unadjuvanted formulation of Arepanrix vaccine on Day 21 and Day 42. All vaccines were administered intramuscularly in the deltoids of the dominant or non dominant arm. At Day 0 the two vaccines were administered each in a separate arm, at Day 21 in the dominant arm and at Day 42 in the non-dominant arm.
干预措施: Saline placebo (Biological)
Flulaval/placebo/Arepanrix Group
subjects received co-administration of Flulaval vaccine and saline placebo on Day 0 followed the administration of Arepanrix vaccine on Day 21 and Day 42. All vaccines were administered intramuscularly in the deltoids of the dominant or non dominant arm. At Day 0 the two vaccines were administered each in a separate arm, at Day 21 in the dominant arm and at Day 42 in the non-dominant arm.
干预措施: Seasonal trivalent influenza vaccine (TIV) (Biological)
Flulaval/placebo/Arepanrix Group
subjects received co-administration of Flulaval vaccine and saline placebo on Day 0 followed the administration of Arepanrix vaccine on Day 21 and Day 42. All vaccines were administered intramuscularly in the deltoids of the dominant or non dominant arm. At Day 0 the two vaccines were administered each in a separate arm, at Day 21 in the dominant arm and at Day 42 in the non-dominant arm.
干预措施: Saline placebo (Biological)
Flulaval/unadjuvanted Arepanrix/placebo Group
subjects received co-administration of Flulaval vaccine and the unadjuvanted formulation of Arepanrix vaccine on Day 0 followed by the administration of the unadjuvanted formulation of Arepanrix vaccine on Day 21 and saline placebo on Day 42. All vaccines were administered intramuscularly in the deltoids of the dominant or non dominant arm. At Day 0 the two vaccines were administered each in a separate arm, at Day 21 in the dominant arm and at Day 42 in the non-dominant arm.
干预措施: GSK2340273A (Biological)
Flulaval/unadjuvanted Arepanrix/placebo Group
subjects received co-administration of Flulaval vaccine and the unadjuvanted formulation of Arepanrix vaccine on Day 0 followed by the administration of the unadjuvanted formulation of Arepanrix vaccine on Day 21 and saline placebo on Day 42. All vaccines were administered intramuscularly in the deltoids of the dominant or non dominant arm. At Day 0 the two vaccines were administered each in a separate arm, at Day 21 in the dominant arm and at Day 42 in the non-dominant arm.
干预措施: Seasonal trivalent influenza vaccine (TIV) (Biological)
Flulaval/unadjuvanted Arepanrix/placebo Group
subjects received co-administration of Flulaval vaccine and the unadjuvanted formulation of Arepanrix vaccine on Day 0 followed by the administration of the unadjuvanted formulation of Arepanrix vaccine on Day 21 and saline placebo on Day 42. All vaccines were administered intramuscularly in the deltoids of the dominant or non dominant arm. At Day 0 the two vaccines were administered each in a separate arm, at Day 21 in the dominant arm and at Day 42 in the non-dominant arm.
干预措施: Saline placebo (Biological)
Flulaval/Arepanrix/placebo Group
subjects received co-administration of Flulaval vaccine and Arepanrix vaccine on Day 0 followed by Arepanrix vaccine on Day 21 and saline placebo on Day 42. All vaccines were administered intramuscularly in the deltoids of the dominant or non dominant arm. At Day 0 the two vaccines were administered each in a separate arm, at Day 21 in the dominant arm and at Day 42 in the non-dominant arm.
干预措施: Seasonal trivalent influenza vaccine (TIV) (Biological)
Flulaval/Arepanrix/placebo Group
subjects received co-administration of Flulaval vaccine and Arepanrix vaccine on Day 0 followed by Arepanrix vaccine on Day 21 and saline placebo on Day 42. All vaccines were administered intramuscularly in the deltoids of the dominant or non dominant arm. At Day 0 the two vaccines were administered each in a separate arm, at Day 21 in the dominant arm and at Day 42 in the non-dominant arm.
干预措施: Saline placebo (Biological)
Unadjuvanted Arepanrix/placebo/Flulaval Group
subjects received co-administration of the unadjuvanted formulation of Arepanrix vaccine and saline placebo on Day 0 followed by the unadjuvanted formulation of Arepanrix vaccine on Day 21 and Flulaval vaccine on Day 42. All vaccines were administered intramuscularly in the deltoids of the dominant or non dominant arm. At Day 0 the two vaccines were administered each in a separate arm, at Day 21 in the dominant arm and at Day 42 in the non-dominant arm.
干预措施: Seasonal trivalent influenza vaccine (TIV) (Biological)
Unadjuvanted Arepanrix/placebo/Flulaval Group
subjects received co-administration of the unadjuvanted formulation of Arepanrix vaccine and saline placebo on Day 0 followed by the unadjuvanted formulation of Arepanrix vaccine on Day 21 and Flulaval vaccine on Day 42. All vaccines were administered intramuscularly in the deltoids of the dominant or non dominant arm. At Day 0 the two vaccines were administered each in a separate arm, at Day 21 in the dominant arm and at Day 42 in the non-dominant arm.
干预措施: Saline placebo (Biological)
Arepanrix/placebo/Flulaval Group
subjects received co-administration of Arepanrix vaccine and saline placebo on Day 0 followed by Arepanrix vaccine on Day 21 and Flulaval vaccine on Day 42. All vaccines were administered intramuscularly in the deltoids of the dominant or non dominant arm. At Day 0 the two vaccines were administered each in a separate arm, at Day 21 in the dominant arm and at Day 42 in the non-dominant arm.
干预措施: Seasonal trivalent influenza vaccine (TIV) (Biological)
Arepanrix/placebo/Flulaval Group
subjects received co-administration of Arepanrix vaccine and saline placebo on Day 0 followed by Arepanrix vaccine on Day 21 and Flulaval vaccine on Day 42. All vaccines were administered intramuscularly in the deltoids of the dominant or non dominant arm. At Day 0 the two vaccines were administered each in a separate arm, at Day 21 in the dominant arm and at Day 42 in the non-dominant arm.
干预措施: Saline placebo (Biological)
结局指标
主要结局
Hemagglutination Inhibition (HI) Antibody Titers Against A/California/7/2009 H1N1 Vaccine Strain.
时间窗: 21 days after the second dose of the unadjuvanted formulation of Arepanrix vaccine (at Day 42)
The A/California vaccine virus-homologous antibody response was measured in subjects having received Flulaval vaccine co-administered with the first dose of the unadjuvanted formulation of Arepanrix vaccine, and in subjects having received two doses of the unadjuvanted formulation of Arepanrix vaccine alone. Titers were expressed as geometric mean antibody titers (GMTs).
次要结局
- Number of Influenza-specific Cluster of Differentiation 8 (CD8) T-cells Per Million Producing Two or More Markers Within Cluster Differentiation 40 Ligand (CD40L), Interleukin-2 (IL-2), Interferon-γ (IFN-γ) and Tumor Necrosis Factor-α (TNF-α).(On Days 0, 7, 21, 28, 42, 63 and 182)
- Number of Subjects Reporting Potential Immune Diseases (pIMDs).(During the entire study period (Days 0-406).)
- Number of Subjects Reporting Serious Adverse Events (SAEs).(During the entire study period (Days 0-329).)
- Number of Influenza-specific Cluster of Differentiation 4 (CD4) T-cells Per Million Producing Two or More Markers Within Cluster Differentiation 40 Ligand (CD40L), Interleukin-2 (IL-2), Interferon-γ (IFN-γ) and Tumor Necrosis Factor-α (TNF-α).(On Days 0, 7, 21, 28, 42, 63 and 182)
- Number of Subjects Reporting Solicited Local Symptoms.(During a 7-day follow-up period (Days 0-6) post-vaccination period)
- Number of Subjects Reporting Unsolicited Adverse Events (AEs).(Within the 84-day (Days 0-83) post-vaccination period.)
- Microneutralization Antibody Titers Against A/California/7/2009 (H1N1) Strain.(On Days 0, 21, 42, 63 and 182)
- Number of Subjects With a Microneutralization Titer Greater Than or Equal to 1:28 for Antibodies Against A/California/7/2009 (H1N1) Strain.(On Days 0, 21, 42, 63 and 182)
- Number of Seroprotected Subjects for Antibodies Against A/California Strain.(At Day 63 for Flulaval/placebo/unadjuvanted Arepanrix and Flulaval/placebo/Arepanrix Groups; At Day 42 for the 4 other groups.)
- Number of Seroconverted Subjects for Antibodies Against Flulaval Vaccine Strains(At Day 182 from Day 0)
- Number of Subjects Reporting Solicited General Symptoms.(During a 7-day follow-up period (Days 0-6) post-vaccination period)
- Vaccine Response Rates (VRR) for Microneutralization Antibody Titers Against A/California/7/2009 (H1N1) Strain.(On Days 0, 21, 42, 63 and 182)
- Number of Seroprotected Subjects for Antibodies Against Flulaval Vaccine Strains(At Day 21 for the pooled group, Flulaval/unadjuvanted Arepanrix/placebo and Flulaval/Arepanrix/placebo Groups; at Day 63 for Unadjuvanted Arepanrix/placebo/Flulaval Group and Arepanrix/placebo/Flulaval Group)
- Seroconversion Factor for Antibodies Against Flulaval Vaccine Strains.(At Day 182 from Day 0)
- Number of Subjects Reporting Medically Attended Visits (MAEs).(During the entire study period (Days 0-368).)
- Geometric Mean Antibody Titers (GMTs) for Hemagglutination Inhibition (HI) Antibodies Against Flulaval Vaccine Strains.(At Day 182 after dose 1 vaccination)
- Hemagglutination Inhibition (HI) Antibody Titers Against A/California/7/2009 H1N1 Vaccine Strain.(21 days after the second dose of the pandemic vaccine (at Day 63))
- Geometric Mean Antibody Titers (GMTs) for Hemagglutination Inhibition (HI) Antibodies Against Flu A/California H1N1 Strain.(At Day 182)
- Number of Seroconverted Subjects for Antibodies Against Flulaval Vaccine Strains.(At Day 21 from Day 0 for the pooled group, Flulaval/unadjuvanted Arepanrix/placebo and Flulaval/Arepanrix/placebo Groups; at Day 63 from Day 42 for Unadjuvanted Arepanrix/placebo/Flulaval Group and Arepanrix/placebo/Flulaval Group)
- Hemagglutination Inhibition (HI) Antibody Titers Against Each of the Three Flulaval Strains.(21 days after the Flulaval vaccination (Day 63 for Unadjuvanted Arepanrix/placebo/Flulaval Group and Day 21 for Flulaval/placebo/unadjuvanted Arepanrix and Flulaval/placebo/Arepanrix Groups))
- Number of Seroconverted Subjects for Antibodies Against A/ California Strain.(At Day 63 from Day 21 for Flulaval/placebo/unadjuvanted Arepanrix and Flulaval/placebo/Arepanrix Groups; At Day 42 from Day 0 for the 4 other groups)
- Seroconversion Factor for Antibodies Against A/California Strain.(At Day 63 from Day 21 for Flulaval/placebo/unadjuvanted Arepanrix and Flulaval/placebo/Arepanrix Groups; At Day 42 from Day 0 for the 4 other groups)
- Number of Seroprotected Subjects for Antibodies Against Flulaval Vaccine Strains.(At Day 182 after the first dose)
- Number of Subjects Reporting Clinical Laboratory Abnormalities in Biochemical and Haematological Parameters Assessed(On Days 0, 7, 21, 28, 42, 63 and 182)