Safety and Immunogenicity of a Candidate Tuberculosis (TB) Vaccine in Healthy HIV Negative Adolescents

Study Overview
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Brief Summary
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This observer blind study will assess the safety and immunogenicity of GSK Biologicals' investigational 692342 vaccine administered at 0, 1 month to healthy adolescents living in a TB-endemic region.

Official Title
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Safety and Immunogenicity Study of GSK Biologicals' Candidate Tuberculosis Vaccine (692342) When Administered to Healthy HIV-negative Adolescents Living in a TB Endemic Region

Conditions
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Tuberculosis

Intervention / Treatment
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* Biological: GSK's investigational vaccine 692342
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that they and their parent(s)/ legal guardian(s) can and will comply with the requirements of the protocol. A male or female between, and including, 13 and 17 years of age at the time of the first vaccination. Written informed consent obtained from the subject's parent(s) or legal guardian(s). Written informed assent obtained from the subject. Free of obvious health problems as established by medical history and clinical examination before entering into the study. Seronegative for HIV-1. No history of TB disease. No active pulmonary disease on chest X-ray. Availability for the duration of the immunisation and follow-up period, with the family not planning to move away from the study area within the next year. 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 is abstinent, has practiced adequate contraception for 30 days prior to vaccination, and has a negative pregnancy test on the day of vaccination, and has agreed to continue adequate contraception during the entire vaccination period and for 2 months after completion of the vaccination series. Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) 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 investigational Mycobacterium tuberculosis vaccines. History of previous exposure to components of the investigational vaccine. Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. Any condition or illness (acute, chronic or history) or medication, which in the opinion of the investigator might interfere with the evaluation of the safety or immunogenicity of the study vaccine. Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of vaccine, or planned administration during the study. Planned participation or participation in another experimental clinical study during the study period. A family history of congenital or hereditary immunodeficiency. Any chronic drug therapy to be continued during the study period, with the exception of vitamins and/or dietary supplements, birth control pills, anti-histamines for seasonal allergies and Specific Serotonin Reuptake Inhibitors (SSRIs). History of allergic reactions (significant IgE-mediated events) or anaphylaxis to any vaccine. History of allergic disease or reactions likely to be exacerbated by any component of the study vaccine. Pregnant female, lactating female or female planning to become pregnant or discontinue contraceptive precautions. Drug and/or alcohol abuse

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br> | Biological: GSK's investigational vaccine 692342<br>* Intramuscular injection, 2 doses<br>|
| Placebo Comparator: Group B<br> | Biological: Placebo<br>* Intramuscular injection, 2 doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site. Relationship analysis was not performed. | During the 7-day (Days 0-6) post-vaccination period following each dose and across doses | 
| Number of Subjects With Solicited General Symptoms | Assessed solicited general symptoms 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. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever ≥ 39.5 °C. Related = symptom assessed by the investigator as related to the vaccination. | During the 7-day (Days 0-6) post-vaccination period following each dose and across doses | 
| Number of Subjects With Unsolicited Adverse Events (AEs) | 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. 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. | During the 30-day (Days 0-29) post-vaccination period | 
| Number of Subjects With Serious Adverse Events (SAEs) | 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. | During the entire study period (from Day 0 up to Day 210) | 
| Number of Subjects With Normal Biochemical and Haematological Levels | Among biochemical and haematological parameters assessed were alanine aminotransferase [ALT], aspartate aminotransferase [AST], creatinine [CREA], haemoglobin [Hgb]. Levels of haematological/biochemical parameters assessed in terms of normal laboratory values were - normal, below and above. | At Day 0, 7, 30, 37 and 60 | 
| Number of Subjects With Normal Haematological Levels | Among haematological parameters assessed were platelets [PLA], red blood cells [RBC] and white blood cells [WBC]. Levels of haematological parameters assessed in terms of normal laboratory values were - normal, below and above. | At Day 0, 7, 30, 37 and 60 | 
| Number of Subjects With Biochemical and Haematological Above Normal Levels | Among biochemical and haematological parameters assessed were alanine aminotransferase [ALT], aspartate aminotransferase [AST], creatinine [CREA], haemoglobin [Hgb]. Levels of haematological/biochemical parameters assessed in terms of normal laboratory values were - normal, below and above. | At Day 0, 7, 30, 37 and 60 | 
| Number of Subjects With Haematological Levels Above Normal | Among haematological parameters assessed were platelets [PLA], red blood cells [RBC] and white blood cells [WBC]. Levels of haematological parameters assessed in terms of normal laboratory values were - normal, below and above. | At Day 0, 7, 30, 37 and 60 | 
| Number of Subjects With Biochemical and Haematological Below Normal Levels | Among biochemical and haematological parameters assessed were alanine aminotransferase [ALT], aspartate aminotransferase [AST], creatinine [CREA], haemoglobin [Hgb]. Levels of haematological/biochemical parameters assessed in terms of normal laboratory values were - normal, below and above. | At Day 0, 7, 30, 37 and 60 | 
| Number of Subjects With Haematological Levels Below Normal | Among haematological parameters assessed were platelets [PLA], red blood cells [RBC] and white blood cells [WBC]. Levels of haematological parameters assessed in terms of normal laboratory values were - normal, below and above. | At Day 0, 7, 30, 37 and 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Mycobacterium Tuberculosis Fusion Protein (M72) Specific Cluster of Differentiation 4/8 (CD4/8+) T Cells Expressing at Least Two Different Cytokines | Among cytokines expressed were interleukin-2 [IL-2], interferon-gamma [IFN-γ], tumour necrosis factor-alpha [TNF-α] and cluster of differentiation 40-ligand [CD40-L]. Analysis of cytokines expression was done by means of in vitro flow cytometry, using intracellular cytokine staining (ICS). | At Day 0, 7, 30, 37, 60 and 210 | 
| Frequency of M72 Specific CD4+ T Cells Expressing Any Combination of Cytokines | Among cytokines expressed were interleukin-2 [IL-2], interferon-gamma [IFN-γ], tumour necrosis factor-alpha [TNF-α] and cluster of differentiation 40-ligand [CD40-L], after background reduction stimulated by M72. Analysis of cytokines expression was done by means of in vitro flow cytometry, using intracellular cytokine staining (ICS). | At Day 0, 7, 30, 37, 60 and 210 | 
| Frequency of M72 Specific CD8+ T Cells Expressing Any Combination of Cytokines | Among cytokines expressed were interleukin-2 [IL-2], interferon-gamma [IFN-γ], tumour necrosis factor-alpha [TNF-α] and cluster of differentiation 40-ligand [CD40-L], after background reduction stimulated by M72. Analysis of cytokines expression was done by means of in vitro flow cytometry, using intracellular cytokine staining (ICS). | At Day 0, 7, 30, 37, 60 and 210 | 
| Anti-M72 Specific Antibody Concentrations | Antibody concentrations given in Enzyme-Linked Immunosorbent Assay (ELISA) units per millilitre (EL.U/mL) were expressed as Geometric Mean Concentrations (GMCs). | At Day 0, 30, 60 and 210 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tuberculosis vaccine