Safety and Immunogenicity Study of GSK Biologicals' Candidate Tuberculosis Vaccine (692342) When Administered to Healthy Infants
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 301
- 试验地点
- 2
- 主要终点
- Number of Subjects With Grade 3 Solicited Local Symptoms After Dose 1, Dose 2 and Across Doses
研究概览
简要总结
This purpose of the study is to assess the safety and immunogenicity of a GSK Biologicals' candidate tuberculosis vaccine (692342) when administered concomitantly with or after the Expanded Programme of Immunisation vaccines regimen to healthy infants aged between and including 2 and 7 months, living in a tuberculosis endemic region.
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
- 2 Months 至 7 Months（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male and female subjects who the investigator believes that their parent(s)/ Legally Acceptable Representative (LAR(s)) can and will comply with the requirements of the protocol.
- •Written or oral, signed or thumb-printed and witnessed informed consent obtained from the subject's parent(s)/LAR(s).
- •Subjects who received their birth dose of Bacille Calmette Guerrin.
- •Healthy subjects as established by medical history and clinical examination before entering into the study.
- •For the 'Outside Expanded Programme on Immunisation' cohort:
- •Must have documented evidence that he/she has completed the primary Expanded Programme on Immunisation regimen at least 1 month prior to planned vaccination with investigational vaccination regimen.
- •Aged between 5 and 7 months at the time of the first study vaccination.
- •For the 'Within EPI' cohort:
- •Must have received the birth dose of Bacille Calmette Guerrin, oral polio vaccine and Hepatitis B vaccine but NO further Expanded Programme on Immunisation vaccines.
- •Aged between 2 and 4 months at the time of the first study vaccination with diphtheria, tetanus, whole cell pertussis/ Haemophilus influenzae type b vaccine + pneumococcal conjugate vaccine + oral polio vaccine.
排除标准
- •Child in care
- •Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal abnormality, as determined by physical examination and/or laboratory screening tests.
- •Laboratory screening tests out of range, which in the investigator's opinion affects the ability of the child to take part in the study.
- •Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
- •A family history of congenital or hereditary immunodeficiency.
- •Major congenital defects.
- •History of any neurological disorders or seizures.
- •Any condition or illness or medication, which in the opinion of the investigator might interfere with the evaluation of the safety or immunogenicity of the study vaccine.
- •Any other findings that the investigator feels would increase the risk of having an adverse outcome from participation in the trial.
- •Acute disease and/or fever at the time of enrolment.
- •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.
- •For the 'Within Expanded Programme on Immunisation' Cohort only: Previous vaccination with diphtheria, tetanus, pertussis, Haemophilus influenzae type b and pneumococcal conjugate vaccine.
- •History of previous administration of experimental Mycobacterium tuberculosis vaccines.
- •Administration of immunoglobulins, blood transfusions and/or other blood products since birth to the first dose of study vaccine or planned administration during the study period.
- •Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
- •Planned participation or concurrently participating in another clinical study at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product.
- •Any chronic drug therapy to be continued during the study period, with the exception of vitamins and/or dietary supplements
- •History of allergic reactions or anaphylaxis to any vaccine.
- •History of any reaction or hypersensitivity likely to be exacerbated by any component of the study vaccines.
- •Severe malnutrition at screening defined as weight-for-age Z-score < -3 standard deviation.
- •Children will not be enrolled if any maternal, obstetrical or neonatal event that has occurred might, in the judgment of the investigator, result in increased neonatal/infant morbidity.
结局指标
主要结局
Number of Subjects With Grade 3 Solicited Local Symptoms After Dose 1, Dose 2 and Across Doses
时间窗: From Day 0 to Day 6
Solicited local symptoms assessed were pain, redness and swelling. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) of injection site.
Number of Subjects With Grade 3 Solicited Local Symptoms After Dose 2, Dose 3 and Across Doses.
时间窗: From Day 0 to Day 6
Solicited local symptoms were only collected after Dose 2 of EPI vaccination. Solicited local symptoms assessed were pain, redness and swelling. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) of injection site.
Number of Subjects With Grade 3 Solicited General Symptoms After Dose 1, Dose 2 and Across Doses.
时间窗: From Day 0 to Day 6
Solicited general symptoms assessed were drowsiness, fever \[defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)\], irritability/fussiness and loss of appetite. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever \> 39.0 °C.
Number of Subjects With Serious Adverse Events (SAEs)
时间窗: From Month 0 to Month 17
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 Subjects With Grade 3 Solicited General Symptoms After Dose 2, Dose 3 and Across Doses.
时间窗: From Day 0 to Day 6
Solicited general symptoms were only collected after Dose 2 of EPI vaccination. Solicited general symptoms assessed were drowsiness, fever \[defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)\], irritability/fussiness and loss of appetite. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever \> 39.0 °C.
Number of Subjects With Grade 3 Unsolicited Adverse Events (AEs)
时间窗: From Day 0 to Day 29
An unsolicited adverse event is 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.
Number of Subjects With Grade 3 Haematological and Biochemical Levels
时间窗: At Month 8
Haematological/Biochemical parameters assessed were: Haemoglobin (Haem), White Blood Cells (WBC), Platelets (PLA), Alanine Aminotransferase (ALA) and Creatinine (CREA). Grade 3 = Haem.: \< 5.0 g/dL; WBC.: 1.0 to 1.4 x 10³/µL; PLA.: \< 25x10³/µL; ALA.: 5.1 to 10.0 x ULN and CREA: 3.1 to 6.0 x ULN.
次要结局
- Number of Seropositive Subjects Against M72 Antigen(Before vaccination (PRE) and after each dose [at 1, 6 and 12 months post-vaccination (M1, M6 and M12)])
- Number of Seropositive Subjects Against Bordetella Pertussis (Anti-BPT)(Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)])
- Number of Seropositive Subjects Against Polio (Anti-Polio1, Anti-Polio2, Anti-Polio3)(Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)])
- Concentration of Antibodies Against M72 Antigen(Before vaccination (PRE) and after each dose [at 1, 6 and 12 months post-vaccination (M1, M6 and M12)])
- Number of Seroprotected Subjects Against Haemophilus Influenzae Type B (Anti-PRP)(Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)])
- Anti-HB Antibody Concentrations(Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)])
- Anti-Polio1, Anti-Polio2, Anti-Polio3 Antibody Titers(Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)])
- Frequency of M. Tuberculosis Fusion Protein M72 (M72)-Specific Cluster of Differentiation (CD)4+ T Cells Per Million Cells Expressing at Least Two Different Immune Markers(Twelve Months post each dose (M12))
- Number of Seroprotected Subjects Against Diphtheria Toxoid (Anti-D) and Tetanus Toxoid (Anti-T)(Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)])
- Anti-BPT Antibody Concentrations(Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)])
- Number of Subjects With Serious Adverse Events (SAEs)(From Day 0 up to 12 months post last vaccination)
- Anti-PRP Antibody Concentrations(Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)])
- Number of Seropositive Subjects Against Streptococcus Pneumoniae (Anti-4, Anti-6B, Anti-9V, Anti-14, Anti-18C, Anti-19F, Anti-23F)(Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)])
- Number of Subjects With S. Pneumoniae Antibody Concentrations ≥ 0.2 Microgram/Milliliter(Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)])
- Number of Subjects With Normal, Grade 1 (G1), Grade 2 (G2) or Grade 4 (G4) Haematological and Biochemical Markers(Before vaccination (PRE))
- Number of Subjects With Normal, G1, G2, or G4 Haematological and Biochemical Markers(Twelve Months post Dose 3 [PIII(M14)])
- Frequency of M. Tuberculosis Fusion Protein M72 (M72)-Specific Cluster of Differentiation (CD)8+ T Cells Per Million Cells Expressing at Least Two Different Immune Markers(Twelve Months after each dose (M12))
- Anti-D, Anti-T Antibody Concentrations(Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)])
- Number of Seropositive Subjects Against Hepatitis B (Anti-HB)(Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)])
- Number of Seropositive Subjects Against Hepatitis B (Anti-HB) With Antibody Concentrations ≥100mIU/mL(Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)])
- Anti-4, Anti-6B, Anti-9V, Anti-14, Anti-18C, Anti-19F, Anti-23F Antibody Concentrations(Before vaccination (PRE) and 1 Month post Dose 3 [PIII(M3)])