Back to resultsSafety and Immunogenicity of 2 Formulations of Tuberculosis Vaccine GSK692342 Given at 0,1 Months to Healthy Adults
Primary Purpose
Tuberculosis
Status
Completed
Phase
Phase 2
Locations
Belgium
Study Type
Interventional
Intervention
GSK's candidate Mycobacterium tuberculosis vaccine 692342
Comparator vaccine with recombinant Mycobacterium tuberculosis antigen and adjuvant system
Comparator vaccine with recombinant Mycobacterium tuberculosis antigen and physiological saline
Control vaccine with the adjuvant system.
Sponsored by
About this trial
This is an interventional prevention trial for Tuberculosis focused on measuring Tuberculosis
Eligibility Criteria
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.
- Free of obvious health problems as established by medical history and clinical examination before entering into the study.
- Subjects must have PPD negative skin reactivity (0 mm induration 48 to 72 hours after PPD skin test administration).
- Clinically normal laboratory values for creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), complete blood count (CBC) and differential, haemoglobin, platelet count and urinalysis.
- Seronegative for human immunodeficiency virus-1 and 2 (HIV 1/2) antibodies, hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) antibodies
- If the subject is female, she must be of non-childbearing potential, or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions for 30 days prior to vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after completion of the vaccination series.
- No evidence of pulmonary pathology (i.e. acute or chronic pulmonary disease; past TB infection/disease) as confirmed by chest X-ray.
Exclusion Criteria:
- History of previous exposure to experimental products containing components of the experimental vaccine.
- 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.
- Chronic administration of immunosuppressants or other immune-modifying drugs within 6 months prior to the first vaccine dose.
- Any chronic drug therapy to be continued during the study period. Vitamins and/or dietary supplements, herbal medications, birth control pills, anti-histamines for seasonal allergies, SSRIs (e.g. Prozac, Zoloft, Paxil), NSAIDs (nonsteroidal anti-inflammatory drugs e.g. aspirin, ibuprofen), and acetaminophen are allowed.
- History of documented exposure to Mycobacterium tuberculosis.
- History of prior vaccination with experimental Mycobacterium tuberculosis vaccines.
- Administration of any immunoglobulins, any immunotherapy and/or any blood products within the 3 months preceding the first dose of study vaccination, or planned administrations during the study period.
- Participation in another experimental protocol during the study period.
- Any confirmed or suspected immunosuppressive or immunodeficient condition; or family history of congenital or hereditary immunodeficiency.
- History of hypersensitivity to vaccines or vaccine components
- History of any acute or chronic illness or medication that, in the opinion of the investigator, may interfere with the evaluation of the safety or immunogenicity of the vaccine.
- Volunteers with a personal history of autoimmune disease or who describe a first-degree relative with clearly documented autoimmune disease.
- History of any neurological disorders or seizures.
- History of chronic alcohol consumption and/or drug abuse.
- History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
- Major congenital defects.
- Pregnant female, lactating female or female planning to become pregnant or planning to discontinue contraceptive precautions.
Sites / Locations
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
M72/AS01B Group
M72/AS02A Group
Mtb72F/AS02A Group
Non-adjuvanted Group
Control Group
Arm Description
Healthy male or female subjects, between and including 18 to 50 years of age, who received 2 doses of M72/AS01B vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 0 and Month 1.
Healthy male or female subjects, between and including 18 to 50 years of age, who received 2 doses of M72/AS02A vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 0 and Month 1.
Healthy male or female subjects, between and including 18 to 50 years of age, who received 2 doses of the comparator Mtb72F/AS02A vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 0 and Month 1.
Healthy male or female subjects, between and including 18 to 50 years of age, who received 2 doses of the comparator GSK Biologicals' candidate recombinant M. tuberculosis vaccine, non-adjuvanted, administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 0 and Month 1.
Healthy male or female subjects, between and including 18 to 50 years of age, who received 2 doses of the adjuvant system alone, administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 0 and Month 1.
Outcomes
Primary Outcome Measures
Number of Subjects With Any and Grade 3 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.
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Assessed solicited general symptoms were fatigue, fever [defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)], gastrointestinal symptoms and headache. 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 causally related to the study vaccination.
Number of Subjects With Any, Grade 3 and Related 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 outside 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.
Number of Subjects With Serious Adverse Events (SAEs)
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 SAEs
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 SAEs
SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Note: Follow-up during Year 2 continued only for the M72/AS01B Group and M72/AS02A Group.
Number of Subjects With SAEs
SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Note: Follow-up during Year 3 continued only for the M72/AS01B Group and M72/AS02A Group.
Number of Subjects With Normal or Abnormal Haematological and Biochemical Levels
Among haematological and biochemical parameters assessed were Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Basophils, Creatinine, Eosinophils, Haemoglobin, Haematocrite, Lymphocytes, Monocytes, Neutrophils, Platelets, Red blood cells (RBC), White blood cells (WBC). Inside = within laboratory reference range; Above = above laboratory reference range; Below = below laboratory reference range.
Number of Subjects With Normal and Abnormal Haematological and Biochemical Levels
Among haematological and biochemical parameters assessed were Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Basophils, Creatinine, Eosinophils, Haemoglobin, Haematocrite, Lymphocytes, Monocytes, Neutrophils, Platelets, Red blood cells (RBC), White blood cells (WBC). Inside = within laboratory reference range; Above = above laboratory reference range; Below = below laboratory reference range.
Number of Subjects With Normal or Abnormal Haematological and Biochemical Levels
Among haematological and biochemical parameters assessed were Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Basophils, Creatinine, Eosinophils, Haemoglobin, Haematocrite, Lymphocytes, Monocytes, Neutrophils, Platelets, Red blood cells (RBC), White blood cells (WBC). Inside = within laboratory reference range; Above = above laboratory reference range; Below = below laboratory reference range.
Number of Subjects With Normal or Abnormal Haematological and Biochemical Levels
Among haematological and biochemical parameters assessed were Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Basophils, Creatinine, Eosinophils, Haemoglobin, Haematocrite, Lymphocytes, Monocytes, Neutrophils, Platelets, Red blood cells (RBC), White blood cells (WBC). Inside = within laboratory reference range; Above = above laboratory reference range; Below = below laboratory reference range.
Number of Subjects With Normal or Abnormal Haematological and Biochemical Levels
Among haematological and biochemical parameters assessed were Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Basophils, Creatinine, Eosinophils, Haemoglobin, Haematocrite, Lymphocytes, Monocytes, Neutrophils, Platelets, Red blood cells (RBC), White blood cells (WBC). Inside = within laboratory reference range; Above = above laboratory reference range; Below = below laboratory reference range.
Levels of C-reactive Protein
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
Levels of C-reactive Protein
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
Levels of C-reactive Protein
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
Levels of C-reactive Protein
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
Levels of C-reactive Protein
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
Levels of C-reactive Protein
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
Levels of Immunoglobulin E
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
Levels of Immunoglobulin E
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
Levels of Immunoglobulin E
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
Levels of Immunoglobulin E
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
Levels of Immunoglobulin E
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
Levels of Immunoglobulin E
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
Secondary Outcome Measures
Antibody Concentrations Against Mycobacterium Tuberculosis (M. Tuberculosis) Fusion Proteins M72 and Mtb72F
Antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in Enzyme-Linked Immunosorbent Assay (ELISA) units per milliliter (EU/mL). The reference seropositivity cut-off values for anti-M72 and anti-Mtb72F antibodies were ≥ 2.8 EU/mL and ≥ 1.0 EU/mL, respectively.
Antibody Concentrations Against M. Tuberculosis Fusion Protein M72
Antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EU/mL). The reference seropositivity cut-off value for anti-M72 antibodies was ≥ 2.8 EU/mL.
Frequency of Mycobacterium Tuberculosis Fusion Protein (M72) Specific Cluster of Differentiation 4/8 (CD4/CD8+) 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]. The analysis of cytokines expression was performed by flow cytometry using intracellular cytokine staining (ICS) on frozen peripheral blood mononuclear cell (PBMCs). Note: No vaccine induced responses were observed for CD8+ T-cells, so no results are presented throughout the record.
Frequency of Mycobacterium Tuberculosis Fusion Protein (M72) Specific Cluster of Differentiation 4 (CD4+) 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]. The analysis of cytokines expression was performed by flow cytometry using intracellular cytokine staining (ICS) on frozen peripheral blood mononuclear cell (PBMCs).
Frequency of M72 Specific CD4+ 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.
Frequency of M72 Specific CD4+ 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.
Number of Subjects With Response to M72-specific CD4+ T-cells Secreting at Least Two Different Cytokines/Activation Markers
The cut-off value used for analysis of the frequency of cells expressing cytokines/immune markers was the 313 CD4+ T-cells per million CD4+ T-cells, i.e. the 95th percentile of the pre-vaccination level of cells expressing cytokines/immune markers.
Number of Subjects With Response to M72-specific CD4+ T-cells Secreting at Least Two Different Cytokines/Activation Markers
The cut-off value used for analysis of the frequency of cells expressing cytokines/immune markers was the 313 CD4+ T-cells per million CD4+ T-cells, i.e. the 95th percentile of the pre-vaccination level of cells expressing cytokines/immune markers.
Concentrations of IFN-γ Produced in Serum Samples
Concentrations are presented as geometric mean concentrations (GMCs), expressed in picogram per milliliter (pg/mL). The reference seropositivity cut-off value was equal to or above (≥) 1 pg/mL.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00397943
Brief Title
Safety and Immunogenicity of 2 Formulations of Tuberculosis Vaccine GSK692342 Given at 0,1 Months to Healthy Adults
Official Title
Safety, Reactogenicity & Immunogenicity of 2 Formulations of Tuberculosis Vaccine GSK692342 Administered Intramuscularly According to a Schedule of 0, 1 Month, to Healthy Adults Aged 18 to 50 Years
Study Type
Interventional
2. Study Status
Record Verification Date
June 2019
Overall Recruitment Status
Completed
Study Start Date
November 15, 2006 (Actual)
Primary Completion Date
December 1, 2009 (Actual)
Study Completion Date
December 1, 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
5. Study Description
Brief Summary
This study will assess the safety and immunogenicity of 2 different formulations of tuberculosis vaccine GSK692342 in healthy adults.
Detailed Description
The study is designed to have a vaccination phase (includes screening, 2 doses of vaccine 1 month apart and follow-up until 1 month post dose 2), which will be performed in an observer blinded manner. This will be followed by 3 years of follow-up which will continue in an open manner.
No new subjects will be recruited at the follow-up phase. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis
Keywords
Tuberculosis
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
110 (Actual)
8. Arms, Groups, and Interventions
Arm Title
M72/AS01B Group
Arm Type
Experimental
Arm Description
Healthy male or female subjects, between and including 18 to 50 years of age, who received 2 doses of M72/AS01B vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 0 and Month 1.
Arm Title
M72/AS02A Group
Arm Type
Experimental
Arm Description
Healthy male or female subjects, between and including 18 to 50 years of age, who received 2 doses of M72/AS02A vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 0 and Month 1.
Arm Title
Mtb72F/AS02A Group
Arm Type
Active Comparator
Arm Description
Healthy male or female subjects, between and including 18 to 50 years of age, who received 2 doses of the comparator Mtb72F/AS02A vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 0 and Month 1.
Arm Title
Non-adjuvanted Group
Arm Type
Active Comparator
Arm Description
Healthy male or female subjects, between and including 18 to 50 years of age, who received 2 doses of the comparator GSK Biologicals' candidate recombinant M. tuberculosis vaccine, non-adjuvanted, administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 0 and Month 1.
Arm Title
Control Group
Arm Type
Placebo Comparator
Arm Description
Healthy male or female subjects, between and including 18 to 50 years of age, who received 2 doses of the adjuvant system alone, administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 0 and Month 1.
Intervention Type
Biological
Intervention Name(s)
GSK's candidate Mycobacterium tuberculosis vaccine 692342
Intervention Description
Intramuscular injection, 2 doses at 0, 1 month
Intervention Type
Biological
Intervention Name(s)
Comparator vaccine with recombinant Mycobacterium tuberculosis antigen and adjuvant system
Intervention Description
Intramuscular injection, 2 doses at 0, 1 month
Intervention Type
Biological
Intervention Name(s)
Comparator vaccine with recombinant Mycobacterium tuberculosis antigen and physiological saline
Intervention Description
Intramuscular injection, 2 doses at 0, 1 month
Intervention Type
Biological
Intervention Name(s)
Control vaccine with the adjuvant system.
Intervention Description
Intramuscular injection, 2 doses at 0, 1 month
Primary Outcome Measure Information:
Title
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Description
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.
Time Frame
During the 7-day (Days 0-6) follow-up period after each vaccine dose and across doses
Title
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Description
Assessed solicited general symptoms were fatigue, fever [defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)], gastrointestinal symptoms and headache. 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 causally related to the study vaccination.
Time Frame
During the 7-day (Days 0-6) follow-up period after each vaccine dose and across doses
Title
Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
Description
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 outside 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.
Time Frame
During the 30-day (Days 0-29) follow-up period after each vaccine dose
Title
Number of Subjects With Serious Adverse Events (SAEs)
Description
SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Time Frame
During the Active Vaccination Phase (from Day 0 up to Month 2)
Title
Number of Subjects With SAEs
Description
SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Time Frame
From Month 2 up to Month 12
Title
Number of Subjects With SAEs
Description
SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Note: Follow-up during Year 2 continued only for the M72/AS01B Group and M72/AS02A Group.
Time Frame
From Month 12 up to Month 24
Title
Number of Subjects With SAEs
Description
SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Note: Follow-up during Year 3 continued only for the M72/AS01B Group and M72/AS02A Group.
Time Frame
From Month 24 up to Month 36
Title
Number of Subjects With Normal or Abnormal Haematological and Biochemical Levels
Description
Among haematological and biochemical parameters assessed were Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Basophils, Creatinine, Eosinophils, Haemoglobin, Haematocrite, Lymphocytes, Monocytes, Neutrophils, Platelets, Red blood cells (RBC), White blood cells (WBC). Inside = within laboratory reference range; Above = above laboratory reference range; Below = below laboratory reference range.
Time Frame
At Day 0
Title
Number of Subjects With Normal and Abnormal Haematological and Biochemical Levels
Description
Among haematological and biochemical parameters assessed were Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Basophils, Creatinine, Eosinophils, Haemoglobin, Haematocrite, Lymphocytes, Monocytes, Neutrophils, Platelets, Red blood cells (RBC), White blood cells (WBC). Inside = within laboratory reference range; Above = above laboratory reference range; Below = below laboratory reference range.
Time Frame
At Day 7
Title
Number of Subjects With Normal or Abnormal Haematological and Biochemical Levels
Description
Among haematological and biochemical parameters assessed were Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Basophils, Creatinine, Eosinophils, Haemoglobin, Haematocrite, Lymphocytes, Monocytes, Neutrophils, Platelets, Red blood cells (RBC), White blood cells (WBC). Inside = within laboratory reference range; Above = above laboratory reference range; Below = below laboratory reference range.
Time Frame
At Day 30
Title
Number of Subjects With Normal or Abnormal Haematological and Biochemical Levels
Description
Among haematological and biochemical parameters assessed were Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Basophils, Creatinine, Eosinophils, Haemoglobin, Haematocrite, Lymphocytes, Monocytes, Neutrophils, Platelets, Red blood cells (RBC), White blood cells (WBC). Inside = within laboratory reference range; Above = above laboratory reference range; Below = below laboratory reference range.
Time Frame
At Day 37
Title
Number of Subjects With Normal or Abnormal Haematological and Biochemical Levels
Description
Among haematological and biochemical parameters assessed were Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Basophils, Creatinine, Eosinophils, Haemoglobin, Haematocrite, Lymphocytes, Monocytes, Neutrophils, Platelets, Red blood cells (RBC), White blood cells (WBC). Inside = within laboratory reference range; Above = above laboratory reference range; Below = below laboratory reference range.
Time Frame
At Day 60
Title
Levels of C-reactive Protein
Description
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
Time Frame
At Day 0
Title
Levels of C-reactive Protein
Description
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
Time Frame
At Day 1
Title
Levels of C-reactive Protein
Description
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
Time Frame
At Day 7
Title
Levels of C-reactive Protein
Description
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
Time Frame
At Day 30
Title
Levels of C-reactive Protein
Description
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
Time Frame
At Day 31
Title
Levels of C-reactive Protein
Description
The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
Time Frame
At Day 37
Title
Levels of Immunoglobulin E
Description
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
Time Frame
At Day 0
Title
Levels of Immunoglobulin E
Description
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
Time Frame
At Day 1
Title
Levels of Immunoglobulin E
Description
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
Time Frame
At Day 7
Title
Levels of Immunoglobulin E
Description
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
Time Frame
At Day 30
Title
Levels of Immunoglobulin E
Description
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
Time Frame
At Day 31
Title
Levels of Immunoglobulin E
Description
The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
Time Frame
At Day 37
Secondary Outcome Measure Information:
Title
Antibody Concentrations Against Mycobacterium Tuberculosis (M. Tuberculosis) Fusion Proteins M72 and Mtb72F
Description
Antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in Enzyme-Linked Immunosorbent Assay (ELISA) units per milliliter (EU/mL). The reference seropositivity cut-off values for anti-M72 and anti-Mtb72F antibodies were ≥ 2.8 EU/mL and ≥ 1.0 EU/mL, respectively.
Time Frame
At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)
Title
Antibody Concentrations Against M. Tuberculosis Fusion Protein M72
Description
Antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EU/mL). The reference seropositivity cut-off value for anti-M72 antibodies was ≥ 2.8 EU/mL.
Time Frame
At Year 2 (Month 24) and Year 3 (Month 36)
Title
Frequency of Mycobacterium Tuberculosis Fusion Protein (M72) Specific Cluster of Differentiation 4/8 (CD4/CD8+) T-cells Expressing at Least Two Different Cytokines
Description
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]. The analysis of cytokines expression was performed by flow cytometry using intracellular cytokine staining (ICS) on frozen peripheral blood mononuclear cell (PBMCs). Note: No vaccine induced responses were observed for CD8+ T-cells, so no results are presented throughout the record.
Time Frame
At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)
Title
Frequency of Mycobacterium Tuberculosis Fusion Protein (M72) Specific Cluster of Differentiation 4 (CD4+) T-cells Expressing at Least Two Different Cytokines
Description
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]. The analysis of cytokines expression was performed by flow cytometry using intracellular cytokine staining (ICS) on frozen peripheral blood mononuclear cell (PBMCs).
Time Frame
At Year 2 (Month 24) and Year 3 (Month 36)
Title
Frequency of M72 Specific CD4+ T-cells Expressing at Least One Cytokine and Another Signal Molecule
Description
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.
Time Frame
At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)
Title
Frequency of M72 Specific CD4+ T-cells Expressing at Least One Cytokine and Another Signal Molecule
Description
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.
Time Frame
At Year 2 (Month 24) and Year 3 (Month 36)
Title
Number of Subjects With Response to M72-specific CD4+ T-cells Secreting at Least Two Different Cytokines/Activation Markers
Description
The cut-off value used for analysis of the frequency of cells expressing cytokines/immune markers was the 313 CD4+ T-cells per million CD4+ T-cells, i.e. the 95th percentile of the pre-vaccination level of cells expressing cytokines/immune markers.
Time Frame
At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)
Title
Number of Subjects With Response to M72-specific CD4+ T-cells Secreting at Least Two Different Cytokines/Activation Markers
Description
The cut-off value used for analysis of the frequency of cells expressing cytokines/immune markers was the 313 CD4+ T-cells per million CD4+ T-cells, i.e. the 95th percentile of the pre-vaccination level of cells expressing cytokines/immune markers.
Time Frame
At Year 2 (Month 24) and Year 3 (Month 36)
Title
Concentrations of IFN-γ Produced in Serum Samples
Description
Concentrations are presented as geometric mean concentrations (GMCs), expressed in picogram per milliliter (pg/mL). The reference seropositivity cut-off value was equal to or above (≥) 1 pg/mL.
Time Frame
Prior to (Day 0 and Day 30) and one day (Day 1 and Day 31) after each vaccination
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Free of obvious health problems as established by medical history and clinical examination before entering into the study.
Subjects must have PPD negative skin reactivity (0 mm induration 48 to 72 hours after PPD skin test administration).
Clinically normal laboratory values for creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), complete blood count (CBC) and differential, haemoglobin, platelet count and urinalysis.
Seronegative for human immunodeficiency virus-1 and 2 (HIV 1/2) antibodies, hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) antibodies
If the subject is female, she must be of non-childbearing potential, or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions for 30 days prior to vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after completion of the vaccination series.
No evidence of pulmonary pathology (i.e. acute or chronic pulmonary disease; past TB infection/disease) as confirmed by chest X-ray.
Exclusion Criteria:
History of previous exposure to experimental products containing components of the experimental vaccine.
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.
Chronic administration of immunosuppressants or other immune-modifying drugs within 6 months prior to the first vaccine dose.
Any chronic drug therapy to be continued during the study period. Vitamins and/or dietary supplements, herbal medications, birth control pills, anti-histamines for seasonal allergies, SSRIs (e.g. Prozac, Zoloft, Paxil), NSAIDs (nonsteroidal anti-inflammatory drugs e.g. aspirin, ibuprofen), and acetaminophen are allowed.
History of documented exposure to Mycobacterium tuberculosis.
History of prior vaccination with experimental Mycobacterium tuberculosis vaccines.
Administration of any immunoglobulins, any immunotherapy and/or any blood products within the 3 months preceding the first dose of study vaccination, or planned administrations during the study period.
Participation in another experimental protocol during the study period.
Any confirmed or suspected immunosuppressive or immunodeficient condition; or family history of congenital or hereditary immunodeficiency.
History of hypersensitivity to vaccines or vaccine components
History of any acute or chronic illness or medication that, in the opinion of the investigator, may interfere with the evaluation of the safety or immunogenicity of the vaccine.
Volunteers with a personal history of autoimmune disease or who describe a first-degree relative with clearly documented autoimmune disease.
History of any neurological disorders or seizures.
History of chronic alcohol consumption and/or drug abuse.
History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
Major congenital defects.
Pregnant female, lactating female or female planning to become pregnant or planning to discontinue contraceptive precautions.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Gent
ZIP/Postal Code
9000
Country
Belgium
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Citations:
PubMed Identifier
22643213
Citation
Leroux-Roels I, Forgus S, De Boever F, Clement F, Demoitie MA, Mettens P, Moris P, Ledent E, Leroux-Roels G, Ofori-Anyinam O; M72 Study Group. Improved CD4(+) T cell responses to Mycobacterium tuberculosis in PPD-negative adults by M72/AS01 as compared to the M72/AS02 and Mtb72F/AS02 tuberculosis candidate vaccine formulations: a randomized trial. Vaccine. 2013 Apr 19;31(17):2196-206. doi: 10.1016/j.vaccine.2012.05.035. Epub 2012 May 27.
Results Reference
background
PubMed Identifier
33493551
Citation
Moris P, Bellanger A, Ofori-Anyinam O, Jongert E, Yarzabal Rodriguez JP, Janssens M. Whole blood can be used as an alternative to isolated peripheral blood mononuclear cells to measure in vitro specific T-cell responses in human samples. J Immunol Methods. 2021 May;492:112940. doi: 10.1016/j.jim.2020.112940. Epub 2021 Jan 23.
Results Reference
derived
Learn more about this trial
Safety and Immunogenicity of 2 Formulations of Tuberculosis Vaccine GSK692342 Given at 0,1 Months to Healthy Adults
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