Reactogenicity and Immunogenicity Study of GlaxoSmithKline Biologicals' Pandemic Influenza Vaccine (GSK1119711A) Administered According to Different Vaccination Schedules
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 512
- 试验地点
- 11
- 主要终点
- Number of Subjects With Any and Grade 3 Solicited Local Symptoms
研究概览
简要总结
The aim of the study is to assess the safety & immunogenicity of a pandemic influenza vaccine administered at 2 different time points. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
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
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study.
- •A male or female between, and including, 18 and 60 years of age at the time of the first vaccination.
- •Written informed consent obtained from the subject.
- •Healthy subjects as established by medical history and clinical examination before entering into the study.
- •If the subject is female, she must be of non-childbearing potential; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions for 30 days prior to first vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after completion of the vaccination series.
排除标准
- •Administration of licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrolment in this study.
- •History of vaccination with investigational influenza pandemic vaccine.
- •History of administration of an experimental/licensed vaccine
- •Planned administration of a vaccine not foreseen by the study protocol during the following periods: from Day 0 up to Day 51; from 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to Month 6 and Month 12; from Month 6 up to Month 6 + 30 days; from Month 12 up to Month 12 + 30 days.
- •Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first administration of the candidate vaccines
- •Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination
- •History of hypersensitivity to vaccines.
- •History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
- •History of chronic alcohol consumption and/or drug abuse.
- •Acute clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
- •Serious chronic disease including any medically significant chronic pulmonary, cardiovascular, renal, neurological, psychiatric or metabolic disorder, as determined by medical history and physical examination.
- •Acute disease at the time of enrolment.
- •Administration of immunoglobulins and/or any blood products within the three months preceding the first administration of the candidate vaccine or during the study.
- •Lactating women.
- •Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days prior to the first vaccination, or planned use during the study period.
- •Any condition which, in the opinion of the investigator, prevents the subject from participation in the study.
研究组 & 干预措施
GSK1562902A V/I/6 Group
Subjects received 1 dose of vaccine formulated from VT strain at Day 0 and 1 dose of the vaccine including IN at Month 6. The vaccine was administered in the deltoid region of the non-dominant arm.
干预措施: Pandemic influenza vaccine (GSK1119711A)-formulation 1 (Biological)
GSK1562902A V/I/6 Group
Subjects received 1 dose of vaccine formulated from VT strain at Day 0 and 1 dose of the vaccine including IN at Month 6. The vaccine was administered in the deltoid region of the non-dominant arm.
干预措施: Pandemic influenza vaccine (GSK1119711A)-formulation 2 (Biological)
GSK1562902A V/V/6 Group
Subjects received 2 doses of vaccine formulated from VT strain, 1 at Day 0 and 1 at Month 6. The vaccine was administered in the deltoid region of the non-dominant arm.
干预措施: Pandemic influenza vaccine (GSK1119711A)-formulation 1 (Biological)
GSK1562902A 2V/I/6 Group
Subjects received 2 doses of vaccine formulated from VT strain, 1 at Day 0 and 1 at Day 21 and a 3rd dose of vaccine including IN strain at Month 6.The vaccine was administered in the deltoid region of the non-dominant arm.
干预措施: Pandemic influenza vaccine (GSK1119711A)-formulation 1 (Biological)
GSK1562902A 2V/I/6 Group
Subjects received 2 doses of vaccine formulated from VT strain, 1 at Day 0 and 1 at Day 21 and a 3rd dose of vaccine including IN strain at Month 6.The vaccine was administered in the deltoid region of the non-dominant arm.
干预措施: Pandemic influenza vaccine (GSK1119711A)-formulation 2 (Biological)
GSK1562902A 2V/V/6 Group
Subjects received 2 doses of vaccine formulated from VT strain, 1 at Day 0 and 1 at Day 21 and a 3rd dose of vaccine including VT strain at Month 6. The vaccine was administered in the deltoid region of the non-dominant arm.
干预措施: Pandemic influenza vaccine (GSK1119711A)-formulation 1 (Biological)
GSK1562902A V/I/12 Group
Subjects received 1 dose of vaccine formulated from VT strain at Day 0 and 1 dose of the vaccine including IN strain at Month 12. The vaccine was administered in the deltoid region of the non-dominant arm.
干预措施: Pandemic influenza vaccine (GSK1119711A)-formulation 1 (Biological)
GSK1562902A V/I/12 Group
Subjects received 1 dose of vaccine formulated from VT strain at Day 0 and 1 dose of the vaccine including IN strain at Month 12. The vaccine was administered in the deltoid region of the non-dominant arm.
干预措施: Pandemic influenza vaccine (GSK1119711A)-formulation 2 (Biological)
GSK1562902A V/V/12 Group
Subjects received 2 doses of vaccine formulated from VT strain, 1 at Day 0 and 1 at Month 12. The vaccine was administered in the deltoid region of the non-dominant arm.
干预措施: Pandemic influenza vaccine (GSK1119711A)-formulation 1 (Biological)
GSK1562902A 2V/I/12 Group
Subjects received 2 doses of vaccine formulated from VT strain, 1 at Day 0 and 1 at Day 21 and a 3rd dose of vaccine including IN strain at Month 12.The vaccine was administered in the deltoid region of the non-dominant arm.
干预措施: Pandemic influenza vaccine (GSK1119711A)-formulation 1 (Biological)
GSK1562902A 2V/I/12 Group
Subjects received 2 doses of vaccine formulated from VT strain, 1 at Day 0 and 1 at Day 21 and a 3rd dose of vaccine including IN strain at Month 12.The vaccine was administered in the deltoid region of the non-dominant arm.
干预措施: Pandemic influenza vaccine (GSK1119711A)-formulation 2 (Biological)
GSK1562902A 2V/V/12 Group
Subjects received 2 doses of vaccine formulated from VT strain, 1 at Day 0 and 1 at Day 21 and a 3rd dose of vaccine including VT strain at Month 12.The vaccine was administered in the deltoid region of the non-dominant arm.
干预措施: Pandemic influenza vaccine (GSK1119711A)-formulation 1 (Biological)
结局指标
主要结局
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
时间窗: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses, up to 6/12 months + 7 days
Assessed solicited local symptoms were ecchymosis, induration, pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 ecchymosis/induration/redness/swelling = spreading beyond 100 millimeters (mm) of injection site.
Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
时间窗: During the entire study period (Day 0 to Month 18)
An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.
Number of Subjects With Serious Adverse Events (SAEs)
时间窗: During the entire study period (Day 0 to Month 18)
Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Number of Booster Seroconverted Subjects Against 2 Strains of Influenza Disease
时间窗: At Month 6 + 21 days
Booster SCR was defined as: For seronegative subjects at pre-booster (Month 6), antibody titer ≥ 1:40 at Month 6 + 7 days; For seropositive subjects at pre-booster (Month 6), antibody titer at Month 6 + 7 days ≥ 4 fold the pre-vaccination antibody titer at Month 6. The 2 flu strains assessed were A/Vietnam/1194/2004 and A/Indonesia/5/2005, for adults who received the booster dose at Month 6.
Number of Subjects With H5N1 Haemagglutination-inhibition (HI) Antibody Concentrations Above the Cut-off Value
时间窗: At Month 6 + 21 Days
The seropositivity cut-off for the assay was an antibody titer equal to or above (≥) 1:10, in the sera of subjects seronegative before vaccination. The flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004, for adults who received the booster dose at Month 6.
Seroconversion Factor for H5N1 Haemagglutination-inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
时间窗: At Month 6 + 21 Days
The seroconversion factor (SCF) was defined as the fold change in serum H5N1 HI geometric mean titers (GMTs) post vaccination compared to Day 0. The 2 flu strains assessed were A/Vietnam/1194/2004 and A/Indonesia/5/2005, for adults who received the booster dose at Month 6.
Number of Seroconverted Subjects for H5N1 Haemagglutination-inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
时间窗: At Month 6 + 21 Days
A seroconverted (SCR) subject was defined as a vaccinated subject who had either a pre-vaccination titer \< 1:10 and a post-vaccination titer ≥ 1:40 or a pre-vaccination titer ≥ 1:10 and at least a four-fold increase in post-vaccination titer. The 2 flu strains assessed were A/Vietnam/1194/2004 and A/Indonesia/5/2005, for adults who received the booster dose at Month 6.
Number of Seroprotected Subjects for H5N1 Haemagglutination-inhibition (HI) Antibodies Against 2 Strains of Influenza Disease
时间窗: At Month 6 + 21 Days
A seroprotected (SPR) subject was defined as a vaccinated subject with serum H5N1 HI titer ≥ 1:40. The 2 flu strains assessed were A/Vietnam/1194/2004 and A/Indonesia/5/2005, for adults who received the booster dose at Month 6.
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
时间窗: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses, up to 12 months + 7 days
Assessed solicited general symptoms were arthralgia, fatigue, fever \[defined as axillary temperature above (\>) 38 degrees Celsius (°C)\], headache, myalgia, shivering and sweating. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever \> 40.0 °C. Related = symptom assessed by the investigator as related to the vaccination.
Booster Factor of H5N1 HI Antibodies Against 2 Strains of Influenza Disease
时间窗: At Month 6 + 21 Days
Booster Factor (Seroconversion Factor booster) was defined as the fold change in H5N1 HI antibodies between the pre- and post-booster vaccination time-points (mean\[log10(POST/M6)\]). The 2 flu strains assessed were A/Vietnam/1194/2004 and A/Indonesia/05/2005, for groups who received the booster dose at Month 6.
Geometric Mean Titers (GMTs) of H5N1 HI Antibodies
时间窗: At Month 6 + 21 Days
GMTs were calculated for H5N1 HI antibodies against the A/Vietnam/1194/2004 or A/Indonesia/05/2005 strains, for the groups who received the booster dose at Month 6.
次要结局
- GMTs of H5N1 HI Antibody Titers, for Groups Who Received Booster Dose at Month 6(At Day 0, Day 21, Day 42, Month 6, Month 6+ 7 Days, Month 6+ 21 Days, Month 12 and at Month 18)
- Seroconversion Factor for H5N1 HI Antibodies Against 2 Strains of Influenza Disease, for Groups Who Received the Booster Dose at Month 6(At Day 21, Day 42, Month 6, Month 6 + 7 Days, Month 6 + 21 Days, Month 12 and Month 18)
- Frequency of Influenza-specific CD4/CD8 T-cells (Per 10E6 T-cells) in Tests Identified as Producing at Least Two Out of Four Different Cytokines, for Groups Who Received Booster Dose at Month 12(At Day 0, Month 6, Month 12, Month 12 + 7 Days, Month 12 + 21 Days and Month 18)
- GMTs of H5N1 Neutralizing Antibodies Against 2 Strains of Influenza Disease, for Groups Who Received Booster Dose at Month 6(At Day 0, Day 21, Day 42, Month 6, Month 6 + 7 Days, Month 6 + 21 Days, Month 12 and Month 18)
- Number of Seroprotected Subjects for H5N1 HI Antibodies Against 2 Strains of Influenza Disease, for Groups Who Received the Booster Dose at Month 12(At Day 0, Day 21, Day 42, Month 6, Month 12, Month 12 + 7 Days, Month 12 + 21 Days)
- GMTs of H5N1 HI Antibodies Against 2 Strains of Influenza Disease for Groups Who Received Booster Dose at Month 12(At Day 0, Day 21, Day 42, Month 6, Month 12, Month 12 + 7 Days, Month 12 + 21 Days and at Month 18)
- Seroconversion Factor for H5N1 HI Antibodies Against 2 Strains of Influenza Disease, for Groups Who Received the Booster Dose at Month 12(At Day 21, Day 42, Month 6, Month 12, Month 12 + 7 Days, Month 12 + 21 Days)
- Number of Booster Seroconverted Subjects Against 2 Strains of Influenza Disease, A/Vietnam/1194/2004 and A/Indonesia/5/2005, for Groups Who Received Booster Dose at Month 12(At Month 12 + 7 Days, Month 12 + 21 Days and Month 18)
- GMTs of H5N1 Neutralizing Antibodies Against 2 Strains of Influenza Disease, for Adults Who Received Booster Dose at Month 6(At Day 0, Day 21, Day 42, Month 6, Month 6 + 7 Days, Month 6 + 21 Days and Month 12)
- GMTs of H5N1 Neutralizing Antibodies Against 2 Strains of Influenza Disease, for Groups Who Received Booster Dose at Month 12(At Day 0, Day 21, Day 42, Month 6, Month 12, Month 12 + 7 Days, Month 12 + 21 Days and Month 18)
- Number of Seroconverted Subjects for H5N1 HI Antibodies Against 2 Strains of Influenza Disease, for Groups Who Received Booster Dose at Month 6(At Day 21, Day 42, Month 6, Month 6 + 7 Days, Month 6 + 21 Days, Month 12 and Month 18)
- Number of Seroprotected Subjects for H5N1 HI Antibodies Against 2 Strains of Influenza Disease, for Groups Who Received Booster Dose at Month 6(At Day 0, Day 21, Day 42, Month 6, Month 6+ 7 Days, Month 6+ 21 Days, Month 12 and Month 18)
- Booster Factor of H5N1 HI Antibodies Against 2 Strains of Influenza Disease, for Groups Who Received Booster Dose at Month 12(At Month 12 + 7 Days, Month 12 + 21 Days and at Month 18)
- Number of Seroconverted Subjects for H5N1 HI Antibodies Against 2 Strains of Influenza Disease, for Groups Who Received Booster Dose at Month 12(At Month 12 + 7 Days, Month 12 + 21 Days and Month 18)
- Frequency of Influenza-specific CD4/CD8 T-cells (Per 10E6 T-cells) in Tests Identified as Producing at Least Two Out of Four Different Cytokines, for Groups Who Received Booster Dose at Month 6(At Day 0, Month 6, Month 6 + 7 Days, Month 6 + 21 Days, Month 12 and Month 18)
- Number of Seroconverted Subjects for H5N1 Neutralizing Antibodies Against 2 Strains of Influenza Disease, for Groups Who Received Booster Dose at Month 6(At Day 21, Day 42, Month 6, Month 6 + 7 Days, Month 6 + 21 Days and Month 12)
- Number of Booster Seroconverted Subjects Against 2 Strains of Influenza Disease, for Groups Who Received Booster Dose at Month 6(At Month 6 + 7 Days, Month 6 + 21 Days, Month 12 and Month 18)
- GMTs of H5N1 Neutralizing Antibodies Against 2 Strains of Influenza Disease, for Adults Who Received Booster Dose at Month 12(At Day 0, Day 21, Day 42, Month 6, Month 12, Month 12 + 7 Days and Month 12 + 21 Days)
- Number of Seroconverted Subjects for H5N1 Neutralizing Antibodies Against 2 Strains of Influenza Disease, for Groups Who Received Booster Dose at Month 12(At Day 21, Day 42, Month 6, Month 12, Month 12 + 7 Days and Month 12 + 21 Days)
- Number of Booster Seroconverted Subjects Against 2 Strains of Influenza Disease, for Groups Who Received Booster Dose at Month 12(At Month 12 + 7 Days, Month 12 + 21 Days and Month 18)