An Observer-blind Study to Evaluate the Safety and Immunogenicity of GSK Biologicals' Influenza Vaccine(s) GSK2789869A Administered in Adults 65 Years of Age and Older
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 363
- 试验地点
- 9
- 主要终点
- Number of Seroconverted (SCR) Subjects for Hemagglutination Inhibition (HI) Antibodies Against the Flu A/Mallard/NL/12/2000 (H7N1) Virus Strain
研究概览
简要总结
The purpose of this placebo controlled study is to evaluate the safety and immunogenicity of different formulations of GSK Biologicals H7N1 influenza vaccine in subjects 65 years of age and older. The study will evaluate safety related events and antibody immune responses to different formulations of study vaccine.
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
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female adults who are 65 years of age and older at the time of first study vaccination.
- •Written informed consent obtained from the subject.
- •Subjects who the investigator believes can and will comply with the requirements of the protocol.
- •Stable health status, as established by medical history and physical exam, and defined by absence of a health event satisfying the definition of a serious adverse event, or a change in an ongoing drug therapy due to therapeutic failure or symptoms of drug toxicity, within 1 month prior to enrollment.
- •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.
排除标准
- •Presence or evidence of neurological or psychiatric diagnoses which, although stable, are deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports.
- •Presence or evidence of substance abuse.
- •Diagnosed with cancer, or treatment for cancer within three years.
- •Persons with a history of cancer who are disease-free without treatment for three years or more are eligible.
- •Persons with a history of histologically-confirmed basal cell carcinoma of the skin successfully treated with local excision only are excepted and are eligible, but other histologic types of skin cancer are exclusionary.
- •Women who are disease-free three years or more after treatment for breast cancer and receiving long-term prophylaxis are eligible.
- •Diagnosed with excessive daytime sleepiness (unintended sleep episodes during the day present almost daily for at least one month), or narcolepsy; or history of narcolepsy in subject's parent, sibling or child.
- •Presence of a temperature ≥ 38.0ºC (≥100.4ºF), or acute symptoms greater than "mild" severity on the scheduled date of first vaccination.
- •Any confirmed or suspected immunosuppressive or immunodeficient condition including history of human immunodeficiency virus (HIV) infection.
- •Receipt of systemic glucocorticoids within 30 days prior to the first dose of study vaccine/placebo, or any other cytotoxic, immunosuppressive or immune-modifying drugs within 6 months of first study vaccine/placebo dose. Topical, intra-articularly injected, or inhaled glucocorticoids, topical calcineurin inhibitors or imiquimod are allowed.
- •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 aspirin, and without a clinically-apparent bleeding tendency, are eligible.
- •An acute evolving neurological disorder or Guillain Barré Syndrome within 42 days of receipt of prior seasonal or pandemic influenza vaccine.
- •Administration of an inactive vaccine within 14 days or of a live attenuated vaccine within 30 days before the first dose of study vaccine/placebo.
- •Planned administration of any vaccine other than the study vaccine/placebo before blood sampling at the Day 42 visit.
- •Previous administration of any H7 vaccine or physician-confirmed H7 disease.
- •Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of study vaccine/placebo, or planned use during the study period.
- •Receipt of any immunoglobulins and/or any blood products within 90 days before the first dose of study vaccine/placebo, or planned administration of any of these products during the study period.
- •Any known or suspected allergy to any constituent of influenza vaccines or component used in the manufacturing process of the study vaccine including a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous influenza vaccine.
- •Any condition which, in the opinion of the investigator, prevents the subject from participating in the study.
结局指标
主要结局
Number of Seroconverted (SCR) Subjects for Hemagglutination Inhibition (HI) Antibodies Against the Flu A/Mallard/NL/12/2000 (H7N1) Virus Strain
时间窗: At Day 42
Seroconversion was defined as: For initially seronegative subjects \[antibody titer below (\<) 10 post-vaccination\], antibody titer greater than or equal to (≥) 40 after vaccination; For initially seropositive subjects (antibody titer ≥ 10 prior to vaccination), antibody titer after vaccination ≥ 4 fold the pre-vaccination antibody titer. The Flu strain assessed was A/mallard/Netherlands/12/2000 NIBRG-63 (H7N1) (Flu A/mallard/NL/12/2000 H7N1).
Geometric Mean Fold Rise (GMFR) for HI Antibodies Against Flu A/Mallard/NL/12/2000 (H7N1) Virus Strain
时间窗: At Day 42
GMFR, also known as seroconversion factor (SCR) or mean geometric increase (MGI), was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination (Day 0) reciprocal HI titer for the vaccine virus.
Number of Subjects With Any Medically-attended Adverse Events (MAEs)
时间窗: From Day 0 up to Day 42
MAEs were defined as events for which the subject received medical attention defined as hospitalization, an emergency room visit, or a visit to or from medical personnel (medical doctor) for any reason. Any MAE(s) = Occurrence of any MAE(s) regardless of intensity grade or relation to vaccination.
Number of Subjects With Any Unsolicited Adverse Events (AEs)
时间窗: From Day 0 up to Day 42
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.
Number of Subjects Who Were Seroprotected for HI Antibodies Against the Flu A/Mallard/NL/12/2000 (H7N1) Virus Strain
时间窗: At Day 42
A seroprotected subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:40, that usually is accepted as indicating protection.
Number of Subjects With Any Potential Immune-mediated Diseases (pIMDs)
时间窗: From Day 0 up to Day 42
Any pIMD was defined as an AE including autoimmune diseases and other mediated inflammatory disorders and assessed by the investigator as specific to the treatment administration.
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
Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = significant pain at rest; prevented normal activities as assessed by inability to attend/do work or school. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site.
Number of Subjects With Abnormal Haematological and Biochemical Laboratory Values
时间窗: At Day 42
Among analysed biochemical parameters were alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], basophils \[BAS\], creatinine \[CRE\], eosinophils \[EOS\], hematocrit \[HEM\], hemoglobin \[HgB\], lymphocytes \[LYM\], monocytes \[MON\], neutrophils \[NEU\], platelets \[PLA\], red blood cells \[RBC\] and white blood cells \[WBC\].
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
Assessed solicited general symptoms were fatigue, gastrointestinal symptoms (symptoms included nausea, vomiting, diarrhoea and/or abdominal pain), headache, joint pain at other location, muscle aches, shivering, sweating and fever \[defined as axillary temperature equal to or above (≥) 38 degrees Celsius (°C)\]. Any = occurrence of the symptom regardless of intensity grade or relationship to vaccination. Grade 3 symptom = general symptom that prevented normal everyday activities as assessed by inability to attend/do work or school, or required intervention of a physician/healthcare provider. Grade 3 fever = temperature \> 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.
Number of Subjects With Serious Adverse Events (SAEs)
时间窗: From Day 0 up to Day 42
SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
次要结局
- Number of Subjects With HI Antibody Concentrations Above the Cut-off Value for Vaccine-heterologous (H7N9)(At Days 0, 21 and 42 and at Months 6 and 12)
- Number of Subjects With HI Antibody Concentrations Above the Cut-off Value for Vaccine-homologous (H7N1)(At Days 0, 21, 42 and Months 6 and 12)
- Geometric Mean Fold Rise (GMFR) for HI Antibodies Against Flu A/Shanghai/2/2013 Strain of Influenza Disease Vaccine-heterologous (H7N9)(At Days 21 and 42 and at Months 6 and 12)
- Number of Subjects With HI Neutralizing Antibody Concentrations Above the Cut-off Value for Vaccine-homologous (H7N1)(At Days 0, 21 and 42 and Month 6)
- Number of Subjects With HI Neutralizing Antibody Concentrations Above the Cut-off Value for Vaccine-heterologous (H7N9)(At Days 0, 21 and 42 and at Month 6)
- Number of Seroprotected (SPR) Subjects Against HI Antibodies for Vaccine-homologous (H7N1)(At Days 0, 21 and 42 and at Months 6 and 12)
- Number of Seroconverted (SCR) Subjects for HI Antibodies for Vaccine-homologous (H7N1)(At Days 21 and 42 and at Months 6 and 12)
- Geometric Mean Fold Rise (GMFR) for HI Antibodies Against Flu A/Mallard/NL/12/2000 Strain of Influenza Disease Vaccine-homologous (H7N1)(At Days 21 and 42 and at Months 6 and 12)
- Number of Seroprotected (SPR) Subjects Against HI Antibodies for Vaccine-heterologous (H7N9)(At Days 0, 21 and 42 and at Months 6 and 12)
- Titers for Antibodies Against Flu A/Mallard/NL/12/2000 Strain of Influenza Disease Vaccine-homologous (H7N1)(At Days 0, 21, 42 and Months 6 and 12)
- Vaccine Response Rate (VRR) for Microneutralization (MN) Antibodies Against the Flu A/Anhui/1/2013 (H7N9) Virus Strain(At Days 21 and 42 and at Month 6)
- Number of Subjects With Any Potential Immune-mediated Diseases (pIMDs)(From Day 42 up to Month 12)
- Titers for Antibodies Against Flu A/Shanghai/2/2013 Strain of Influenza Disease Vaccine-heterologous (H7N9)(At Days 0, 21 and 42 and at Months 6 and 12)
- Number of Seroconverted (SCR) Subjects for HI Antibodies for Vaccine-heterologous (H7N9)(At Days 21 and 42 and at Months 6 and 12)
- Titers for Serum Neutralizing Antibodies Against Flu A/Mallard/NL/12/2000 Strain of Influenza Disease Vaccine-homologous (H7N1)(At Days 0, 21 and 42 and at Month 6)
- Titers for Antibodies Against Flu A/Anhui/1/2013 Strain of Influenza Disease Vaccine-homologous (H7N9)(At Days 0, 21 and 42 and at Month 6)
- Vaccine Response Rate (VRR) for Microneutralization (MN) Antibodies Against the Flu A/Mallard/NL/12/2000 (H7N1) Virus Strain(At Days 21 and 42 and at Month 6)
- Number of Subjects With Any Medically-attended Adverse Events (MAEs)(From Day 42 up to Month 12)
- Number of Subjects With Any Unsolicited Adverse Events (AEs)(During the 21-day (From Day 0 to Day 20) post-vaccination period after each dose)
- Number of Subjects With Serious Adverse Events (SAEs)(During the entire study period (From Day 0 up to Month 12))