Safety and Immunogenicity of GSK Biologicals' Candidate Tuberculosis Vaccine (692342) When Administered to HIV-positive Adults Living in a Tuberculosis Endemic Region
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 240
- 试验地点
- 2
- 主要终点
- Number of Subjects With Grade 3 Solicited Local Symptoms
研究概览
简要总结
The purpose of the study is to assess the safety and immunogenicity of a GlaxoSmithKline (GSK) Biologicals' candidate tuberculosis vaccine (692342) administered to Human Immunodeficiency Virus (HIV)-positive adults aged 18 to 59 years, living in a tuberculosis endemic region.
Subjects will be followed-up for 3 years.
Subjects will be enrolled in 3 cohorts:
- HIV-positive adults on highly active antiretroviral therapy
- HIV-positive adults not on highly active antiretroviral therapy
- HIV-negative adults
Each cohort will have 2 groups.
详细描述
This Protocol Posting has been updated following Protocol Amendment 1, February 2011, leading to the update of the outcome measures and the inclusion and exclusion criteria.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 59 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.
- •A male or female between, and including, 18 and 59 years of age at the time of the first vaccination.
- •Written informed consent obtained from the subject prior to any study procedure.
- •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,
- •has a negative pregnancy test on the day of vaccination, and
- •has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series.
- •Clinically acceptable laboratory values at screening as determined by the investigator.
- •No evidence of tuberculosis disease with no evidence of pulmonary pathology as confirmed by chest X-ray.
- •No history of extra pulmonary tuberculosis.
- •Based on their medical history, all subjects must have no history of chemotherapy for tuberculosis.
- •Additional inclusion criteria for subjects to be enrolled in HIV+ on highly active antiretroviral therapy cohort:
- •Subjects must be HIV-positive and under care of a physician for at least 6 months.
- •Subjects must have a CD4+T cell count >= 250 cells/mm3 at screening.
- •Subjects must be stable on highly active antiretroviral therapy for at least 6 months, with an undetectable HIV viral load level at screening.
- •Additional inclusion criteria for subjects to be enrolled in HIV+ treatment naïve cohort:
- •Subjects must be HIV-positive and under care of a physician for at least 6 months
- •Subjects must be highly active antiretroviral therapy-naïve (never received anti-retroviral therapy after HIV diagnosis)
- •Subjects must have a CD4 + T cell count above 350 cells/mm3 at screening.
- •Subjects for whom commencement of highly active antiretroviral therapy is not expected based on current assessment within next year.
- •Subjects must have a viral load between 5000 - 80000 copies/mL at screening.
- •Additional inclusion criteria for subjects to be enrolled in HIV-negative cohort
- •Subjects must be negative for HIV-1.
排除标准
- •Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.
- •Administration of a registered live vaccine not foreseen by the study within 30 days preceding the first dose of study vaccine and administration of a registered inactivated vaccine within 14 days preceding the first dose of study vaccine.
- •History of previous administration of experimental Mtb vaccines.
- •History of previous exposure to components of the investigational vaccine within 30 days preceding the first dose of study vaccine
- •Chronic administration of immunosuppressant or other immune-modifying drugs within six months prior to the first vaccine/product dose. For corticosteroids, this will mean prednisone >= 20 mg/kg/day, or equivalent. 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.
- •Planned participation or participation in another experimental protocol with an experimental product during the study period.
- •Administration of any immunoglobulin, any immunotherapy and/or any blood products within the three months preceding the first dose of study vaccination, or planned administrations during the study period.
- •Subjects taking any of the following medication: chronic administration of systemic steroids, interleukins, systemic interferon or systemic chemotherapy.
- •History of allergic reactions or anaphylaxis to any drug or vaccine.
- •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 which in the Investigator's opinion would put the subject at risk.
- •Pregnant female, lactating female or female planning to become pregnant or stop contraception.
- •Acute or chronic clinically relevant pulmonary, cardiovascular, hepatic or renal function abnormality as determined by physical examination or laboratory screening tests.
- •Additional exclusion criteria for subjects to be enrolled in HIV+ on highly active antiretroviral therapy cohort:
- •Any change in anti-retroviral drug regimen within 12 weeks prior to screening.
- •Any chronic drug therapy, other than highly active antiretroviral therapy or prophylaxis for opportunistic HIV related infections, birth control pills, anti-histamines for seasonal allergies and SSRIs.
研究组 & 干预措施
HIV(+)-HA/GSK692342
HIV-infected subjects between and including 18 to 59 years of age, who were on Highly Active Anti-Retroviral Therapy (HAART) at the time of study enrolment, received two doses of GSK692342 vaccine (TB) at Day 0 and Day 30, intramuscularly into the arm's deltoid region.
干预措施: GSK's investigational vaccine 692342 (Biological)
HIV(+)-HA/Placebo
HIV-infected subjects between and including 18 to 59 years of age, who were on Highly Active Anti-Retroviral Therapy (HAART) at the time of study enrolment, received two doses of saline solution at Day 0 and Day 30, intramuscularly into the arm's deltoid region.
干预措施: Physiological saline (Biological)
HIV(+)-TN/GSK692342
HIV-infected subjects between and including 18 to 59 years of age, who were HAART-treatment naive (TN) at the time of study enrolment, received two doses of GSK692342 vaccine (TB) at Day 0 and Day 30, intramuscularly into the arm's deltoid region.
干预措施: GSK's investigational vaccine 692342 (Biological)
HIV(+)-TN/Placebo
HIV-infected subjects between and including 18 to 59 years of age, who were HAART-treatment naive (TN) at the time of study enrolment, received two doses of saline solution at Day 0 and Day 30, intramuscularly into the arm's deltoid region.
干预措施: Physiological saline (Biological)
HIV(-)/GSK692342
Subjects between and including 18 to 59 years of age, who were HIV-negative at the time of study enrolment, received two doses of GSK692342 vaccine (TB) at Day 0 and Day 30, intramuscularly into the arm's deltoid region.
干预措施: GSK's investigational vaccine 692342 (Biological)
HIV(-)/Placebo
Subjects between and including 18 to 59 years of age, who were HIV-negative at the time of study enrolment, received two doses of saline solution at Day 0 and Day 30, intramuscularly into the arm's deltoid region.
干预措施: Physiological saline (Biological)
结局指标
主要结局
Number of Subjects With Grade 3 Solicited Local Symptoms
时间窗: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
Solicited local symptoms assessed were pain and swelling. Grade 3 pain = pain that prevented normal activity. Grade 3 swelling = swelling spreading beyond 50 millimeters (mm) of injection site.
Number of Subjects With Grade 3 and Grade 4 Haematological and Biochemical Levels
时间窗: At Day 0
Haematological and biochemical parameters assessed were haemoglobin \[Hgb\], white blood cells \[WBC\], platelets \[PLA\], alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\] and creatinine \[CREA\]. The haematology and biochemistry toxicity grading scale was based on the Guidance for Industry - Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.
Number of Subjects With Grade 3 Solicited General Symptoms
时间窗: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
Solicited general symptoms assessed were fatigue, temperature \[defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)\], gastrointestinal symptoms (gastro) \[nausea, vomiting, diarrhoea and/or abdominal pain\], headache, malaise and myalgia. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever ≥ 39.5 °C.
Number of Subjects With Grade 3 and 4 Haematological and Biochemical Levels
时间窗: At Day 7
Haematological and biochemical parameters assessed were haemoglobin \[Hgb\], white blood cells \[WBC\], platelets \[PLA\], alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\] and creatinine \[CREA\]. The haematology and biochemistry toxicity grading scale was based on the Guidance for Industry - Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.
Number of Subjects With Grade 3 and Grade 4 Haematological/Biochemical Levels
时间窗: At Day 30
Haematological and biochemical parameters assessed were haemoglobin \[Hgb\], white blood cells \[WBC\], platelets \[PLA\], alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\] and creatinine \[CREA\]. The haematology and biochemistry toxicity grading scale was based on the Guidance for Industry - Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.
Number of Subjects With Grade 3-4 Haematological and Biochemical Levels
时间窗: At Day 37
Haematological and biochemical parameters assessed were haemoglobin \[Hgb\], white blood cells \[WBC\], platelets \[PLA\], alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\] and creatinine \[CREA\]. The haematology and biochemistry toxicity grading scale was based on the Guidance for Industry - Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.
Number of Subjects With Grade 3-4 Haematological/Biochemical Levels
时间窗: At Day 60
Haematological and biochemical parameters assessed were haemoglobin \[Hgb\], white blood cells \[WBC\], platelets \[PLA\], alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\] and creatinine \[CREA\]. The haematology and biochemistry toxicity grading scale was based on the Guidance for Industry - Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.
Number of Subjects With Grade 3 Unsolicited Adverse Events (AEs)
时间窗: During the 30-day (Days 0-29) post-vaccination period
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 out-side the specified period of follow-up for solicited symptoms. Grade 3 AE = an AE which prevented normal, everyday activities.
Number of Subjects With Serious Adverse Events (SAEs)
时间窗: From screening up to one month post Dose 2
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.
次要结局
- Anti-Mycobacterium Tuberculosis Fusion Protein (M72) Specific Antibody Concentrations(At Days 0, 30, 60, 210 and at Years 1, 2 and 3)
- Number of Seroconverted Subjects for M72-specific Antibodies(At Days 0, 30, 60, 210 and at Years 1, 2 and 3)
- Frequency of M72-cluster of Differentiation 4 (CD4+) T-cells Expressing at Least 2 Immune Markers(At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3)
- Frequency of M72-CD4+ T-cells Expressing Any Combination of Cytokines(At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3)
- M72-CD4+ T-cells Frequency Expressing Any Combination of Cytokines(At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3)
- Frequency of M72-CD8+ T-cells Expressing Any Combination of Cytokines(At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3)
- Frequency of M72-cluster of Differentiation 8 (CD8+) T-cells Expressing at Least 2 Immune Markers(At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3)
- Number of Subjects With Any Solicited Local Symptoms(During the 7-day (Days 0-6) post-vaccination period following each dose and across doses)
- Number of Subjects With SAEs(From one month post Dose 2 up to study end (Year 3))
- M72-CD8+ T-cells Frequency Expressing Any Combination of Cytokines(At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3)
- Number of Subjects With Any Solicited General Symptoms(During the 7-day (Days 0-6) post-vaccination period following each dose and across doses)
- Number of Subjects With Any Unsolicited AEs(During the 30-day (Days 0-29) post-vaccination period)
- M72-cluster of Differentiation 8 (CD8+) T Frequency Cells Expressing Any Combination of Cytokines(At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3)
- Number of Subjects Presenting Different Grades of Haematological and Biochemical Values(At Days 0, 7, 30, 37 and 60)
- M72-cluster of Differentiation 4 (CD4+) T-cells Frequency Expressing Any Combination of Cytokines(At Days 0, 7, 30, 37, 60, 210 and at Years 1, 2 and 3)