Safety and Immunogenicity of a Candidate Tuberculosis (TB) Vaccine in HIV-positive Adults.

Study Overview
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Brief Summary
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This study will assess the safety and immunogenicity of a GSK Biologicals' candidate TB vaccine (692342) administered at 0, 1 month to HIV-positive adults living in Switzerland.

Official Title
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Safety and Immunogenicity of a Candidate Tuberculosis (TB) Vaccine (692342) in HIV-positive Adults.

Conditions
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Tuberculosis

Intervention / Treatment
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* Biological: GSK's candidate Mycobacterium tuberculosis vaccine 692342
* Biological: Control vaccine with the adjuvant system.
* Biological: Control vaccine with physiological saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 50 years of age at the time of the first vaccination. Written informed consent obtained from the subject prior to any study procedure. Subjects must be HIV-positive and must have: received Highly Active Antiretroviral therapy for a minimum of 12 consecutive months prior to screening documented suppressed HIV-1 RNA levels following HAART-treatment. a protocol defined CD4+ T cell count at screening If the subject is female, she must be of non-childbearing potential, or she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for 2 months after completion of vaccination. Clinically acceptable laboratory values prior to randomisation as determined by the Investigator. No evidence of TB disease with no pulmonary pathology as confirmed by chest X-ray. No history of extrapulmonary TB. No history of chemotherapy for TB. Exclusion Criteria: Any change in antiretroviral drug regimen within 12 weeks prior to screening. 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 experimental Mycobacterium tuberculosis vaccines. History of previous exposure to experimental products containing components of the experimental vaccine. Chronic administration of immunosuppressive or other immune-modifying drugs within six months prior to the first vaccine dose. Administration of any immunoglobulins, 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. 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 vaccine. Planned participation or participation in another experimental protocol during the study period. A family history of congenital or hereditary immunodeficiency. •Any chronic drug therapy, other than HAART or prophylaxis for opportunistic HIV-related infections to be continued during the study period. Vitamins and/or dietary supplements, birth control pills, anti-histamines for seasonal allergies and SSRIs are allowed. Subjects taking any of the following medication: systemic steroids, interleukins, systemic interferons or systemic chemotherapy. History of allergic reactions or anaphylaxis to any 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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>Subjects receiving the candidate vaccine | Biological: GSK's candidate Mycobacterium tuberculosis vaccine 692342<br>* Intramuscular injection, 2 doses at 0, 1 month<br>|
| Placebo Comparator: Group B<br>Subjects receiving the adjuvant | Biological: Control vaccine with the adjuvant system.<br>* Intramuscular injection, 2 doses at 0, 1 month<br>|
| Placebo Comparator: Group C<br>Subjects receiving physiological saline | Biological: Control vaccine with physiological saline<br>* Intramuscular injection, 2 doses at 0, 1 month<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 period (Days 0-6) post vaccination following each dose | 
| 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 period (Days 0-6) post vaccination following each dose | 
| 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 period (Days 0-29) post vaccination | 
| 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], basophils [BAS], creatinine [CREA], eosinophil [EOS]. Levels of haematological/biochemical parameters assessed in relation to normal laboratory values were - normal, below and above. | At Day 0, 7, 30, 37 and 60 | 
| Number of Subjects With Normal Haematological Levels | Among biochemical and haematological parameters assessed were haematocrit [Hct], haemoglobin [Hgb], lymphocytes [LYM], monocytes [MON], neutrophils [NEU]. Levels of haematological/biochemical parameters assessed in relation to normal laboratory values were - normal, below and above. | At Day 0, 7, 30, 37 and 60 | 
| Number of Subjects With Normal Haematological Levels | Among biochemical and haematological parameters assessed were platelets [PLA], red blood cells [RBC] and white blood cells [WBC]. Levels of haematological/biochemical parameters assessed in relation to normal laboratory values were - normal, below and above. | At Day 0, 7, 30, 37 and 60 | 
| Number of Subjects With Biochemical and Haematological Levels Below Normal | Among biochemical and haematological parameters assessed were alanine aminotransferase [ALT], aspartate aminotransferase [AST], basophils [BAS], creatinine [CREA], eosinophil [EOS]. Levels of haematological/biochemical parameters assessed in relation to 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 biochemical and haematological parameters assessed were haematocrit [Hct], haemoglobin [Hgb], lymphocytes [LYM], monocytes [MON], neutrophils [NEU]. Levels of haematological/biochemical parameters assessed in relation to 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 biochemical and haematological parameters assessed were [PLA], red blood cells [RBC] and white blood cells [WBC]. Levels of haematological/biochemical parameters assessed in relation to normal laboratory values were - normal, below and above. | At Day 0, 7, 30, 37 and 60 | 
| Number of Subjects With Biochemical and Haematological Levels Above Normal | Among biochemical and haematological parameters assessed were alanine aminotransferase [ALT], aspartate aminotransferase [AST], basophils [BAS], creatinine [CREA], eosinophil [EOS]. Levels of haematological/biochemical parameters assessed in relation to 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 biochemical and haematological parameters assessed were haematocrit [Hct], haemoglobin [Hgb], lymphocytes [LYM], monocytes [MON], neutrophils [NEU]. Levels of haematological/biochemical parameters assessed in relation to 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 biochemical and haematological parameters assessed were [PLA], red blood cells [RBC] and white blood cells [WBC]. Levels of haematological/biochemical parameters assessed in relation to 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] and/or interferon-gamma [IFN-γ] and/or tumour necrosis factor-alpha [TNF-α] and/or 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, 30, 60 and 210 | 
| Frequency of M72 Specific CD4/8+ T Cells Expressing at Least One Cytokine and Another Signal Molecule | Expressed cytokine combinations for CD4+ T cells were CD40-L and interleukin-2 [IL-2] or interferon-gamma [IFN-γ] or tumour necrosis factor-alpha [TNF-α]; IL-2 and CD40-L, or IFN-γ, or TNF-α; IFN-γ and CD40-L, or IL-2, or TNF-α; TNF-α and CD40-L, or IL-2, or IFN-γ. For CD8+ T cells no vaccine induced responses were observed, thus results are presented only for the frequency of M72-specific CD8+ T cells expressing at least two cytokines. | At Day 0, 30, 60 and 210 | 
| Cell Count of CD4+ T Cells | CD4+ T cell counts are defined by values greater than (>) 200 cells per cubic millimeters (mm3) at screening for enrolment into the study. | At Day 0, 30, 60 and 210 | 
| Anti-M72 Specific Antibody Concentrations | Concentrations given in Enzyme-Linked Immunosorbent Assay units per milliliter (EL.U/mL) were expressed in Geometric Mean Concentrations (GMCs). | At Day 0, 30, 60 and 210 | 
| Number of Subjects With Significant Highly Active Anti-Retroviral Therapy (HAART) Changes | Recorded significant HAART change refers to one subject switching the Combivir drug to Truvada as planned by personal physician, with no relationship to vaccination, prior to study enrolment. | From Day 60 to Day 210 | 

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