Efficacy of GSK Biologicals' Candidate Tuberculosis (TB) Vaccine GSK 692342 Against TB Disease, in Adults Living in a TB Endemic Region
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 3,575
- 试验地点
- 9
- 主要终点
- Incident Rates of Definite Pulmonary Tuberculosis (TB) Disease, Not Associated With HIV-infection, Meeting the Case Definition 1
研究概览
简要总结
The purpose of this study is to evaluate the protective efficacy of two doses of GSK Biologicals' candidate TB vaccine against pulmonary TB, as compared to placebo. The efficacy will be evaluated in adults living in TB endemic countries and aged 18 - 50 years because pulmonary TB occurs frequently in these countries and age range. In addition, the safety and immunogenicity of the candidate tuberculosis vaccine will be evaluated in a subset of volunteers.
详细描述
Case Definitions:
• First case definition: A subject with clinical suspicion of pulmonary TB disease, with MTB complex identified from a sputum specimen, taken before initiation of TB treatment, by Xpert MTB/RIF and/or microbiological culture and confirmed HIV-negative at the time of TB diagnosis.
• Second case definition: A subject with clinical suspicion of pulmonary TB disease, with MTB complex identified from a sputum specimen, taken before initiation of TB treatment, by Xpert MTB/RIF and confirmed HIV-negative at the time of TB diagnosis.
• Third case definition: A subject with clinical suspicion of pulmonary TB disease, with MTB complex identified from a sputum specimen, taken up to four weeks after initiation of TB treatment, by Xpert MTB/RIF and/or microbiological culture and confirmed HIV-negative at the time of TB diagnosis.
• Fourth case definition: A subject with clinical suspicion of pulmonary TB disease, with MTB complex identified from a sputum specimen, taken up to four weeks after initiation of TB treatment, by Xpert MTB/RIF and/or microbiological culture.
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
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
- •A male or female between, and including, 18 and 50 years of age at the time of obtaining informed consent.
- •Written (or thumb printed and witnessed) informed consent obtained from the subject.
- •Baseline positive IGRA test result.
- •Baseline negative HIV screen.
- •Baseline negative clinical screening questionnaire and negative sputum sample for Pulmonary TB disease.
- •Healthy subjects or those with chronic well-controlled disease as established by medical history and clinical examination.
- •Female subjects of non-childbearing potential may be enrolled in the study.
- •Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause.
- •Female subjects of childbearing potential may be enrolled in the study, if the subject:
- •has practiced adequate contraception for 25 days prior to vaccination, and
- •has a negative pregnancy test on the day of screening and the day of first vaccination, and
- •has agreed to continue adequate contraception during the entire vaccination period and for 2 months after completion of the vaccination series.
排除标准
- •Current TB disease or history of TB disease and/or treatment for TB.
- •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.
- •Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before and ending 30 days after each dose of vaccine.
- •History of previous administration of experimental Mtb vaccines.
- •Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. Inhaled and topical steroids are allowed.
- •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 vaccine.
- •Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
- •Planned participation or participation in another experimental protocol during the study.
- •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.
- •Administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.
- •History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
- •History of medically confirmed autoimmune disease.
- •Pregnant or lactating female.
- •Female planning to become pregnant or planning to discontinue contraceptive precautions during the vaccination period and/or before 2 months after completion of the vaccination series.
结局指标
主要结局
Incident Rates of Definite Pulmonary Tuberculosis (TB) Disease, Not Associated With HIV-infection, Meeting the Case Definition 1
时间窗: From Day 60 (i.e one month after Dose 2) up to Year 3: follow-up period for cases ends at the first occurrence of an event. For the non-cases: follow-up period ends at the date of the Month 36 visit or last contact date whichever comes first
The incidence rate of definite pulmonary TB disease (or 100 Person-years rate) was calculated as the number of subjects reporting at least one case (n) in a group, over the sum of follow-up period expressed in years (T) in the same group, and multiplied by 100. Case definition 1 = subject with clinical suspicion of pulmonary TB disease\*, with Mycobacterium tuberculosis (Mtb) complex identified from sputum specimen, taken before initiation of TB treatment, by Xpert MTB/RIF (Nucleic Acid Amplification Test to detect Mtb complex and resistance to rifampicin in sputum samples) and/or microbiological culture and confirmed Human Immunodeficiency Virus (HIV)-negative at the time of TB diagnosis. \*Clinical suspicion of pulmonary TB defined as subject presenting with 1 or more of the following symptoms: unexplained cough \> 2 weeks, unexplained fever \> 1 week, night sweats, unintentional weight loss, pleuritic chest pains, haemoptysis, fatigue or shortness of breath on exertion.
次要结局
- Number of Subjects With Any Potential Immune-mediated Diseases (pIMDs)(From Day 0 to 6 months post-dose 2 (i.e. at Month 7))
- Number of Subjects With Any Unsolicited Adverse Events (AEs).(During the 30-day follow-up period following vaccination, across doses (i.e. day of vaccination and 29 subsequent days after each vaccine dose))
- Number of Subjects With Grade Equal or Greater Than 2 of Severity for Haematological and Biochemichal Abnormal Laboratory Values in the Safety and Immune Sub-cohort(Days 0, 7, 30 and 37)
- Number of Subjects With Serious Adverse Events (SAEs).(From Day 0 up to Year 3 (during the entire study period))
- Number of Subjects With Any Solicited General AEs in the Safety and Immune Sub-cohort(During the 7-day follow-up period (i.e.: day of vaccination and 6 subsequent days) after each vaccine dose)
- Incident Rates of Definite Xpert MTB/Rif Positive Pulmonary TB Disease, Not Associated With HIV-infection, Meeting the Case Definition 2(From Day 60 (i.e one month after Dose 2) up to Year 3: follow-up period for cases ends at the first occurrence of an event. For the non-cases: follow-up period ends at the date of the Month 36 visit or last contact date whichever comes first)
- Number of Subjects With Any Solicited Local AEs in the Safety and Immune Sub-cohort(During the 7-day follow-up period (i.e. day of vaccination and 6 subsequent days) after each vaccine dose)
- Incident Rates of Definite Pulmonary TB Disease, Not Associated With HIV-infection Meeting the Case Definition 3(From Day 60 (i.e one month after Dose 2) up to Year 3: follow-up period for cases ends at the first occurrence of an event. For the non-cases: follow-up period ends at the date of the Month 36 visit or last contact date whichever comes first)
- Desciptive Statistics of the Frequency of M72-specific CD4+ T-cells Expressing Any Combination of Immune Markers in the Safety and Immune Sub-cohort(Prior to dose 1 (Day 0) and post-dose 2 (Day 60, Year 1, Year 2 and Year 3))
- Incident Rates of Microbiological Pulmonary TB Disease, Meeting the Case Definition 4(From Day 60 (i.e one month after Dose 2) up to Year 3: follow-up period for cases ends at the first occurrence of an event. For the non-cases: follow-up period ends at the date of the Month 36 visit or last contact date whichever comes first)
- Incidence Rates of Clinical TB Disease, Meeting the Case Definition 5(From Day 60 (i.e one month after Dose 2) up to Year 3: follow-up period for cases ends at the first occurrence of an event. For the non-cases: follow-up period ends at the date of the Month 36 visit or last contact date whichever comes first)
- Desciptive Statistics of the Frequency of M72-specific CD8+ T-cells Expressing Any Combination of Immune Markers in the Safety and Immune Sub-cohort(Prior to dose 1 (Day 0) and post-dose 2 (Day 60, Year 1, Year 2 and Year 3))
- M72-specific Antibody Concentrations as Measured by Enzyme Linked Immuno Sorbent Assay (ELISA) in the Safety and Immune Sub-cohort(Prior to dose 1 (Day 0) and post-dose 2 (Day 60, Year 1, Year 2 and Year 3))
- Number of Seropositive Subjects for M72 Antibodies Measured by ELISA in the Safety and Immune Sub-cohort(Prior to dose 1 (Day 0) and post-dose 2 (Day 60, Year 1, Year 2 and Year 3))