Back to resultsStudy to Evaluate the Efficacy of GlaxoSmithKline (GSK) Biologicals' Candidate Tuberculosis (TB) Vaccine in Adults
Primary Purpose
Tuberculosis, Tuberculosis Vaccines
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
GSK Biologicals' investigational TB vaccine (GSK692342)
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Tuberculosis focused on measuring Positive Interferon-γ release assay, Efficacy, Adults, Tuberculosis vaccine, Endemic region
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
M72AS01 Group
Control group
Arm Description
Subjects, between, and including, 18 and 50 years of age, who received 2 doses of M72/AS01E according to random assignment, one month apart (Day 0 and Day 30) by intramuscular injection in the deltoid region of the arm.
Subjects, between, and including,18 and 50 years of age, who received 2 doses of Placebo according to random assignment, one month apart (Day 0 and Day 30) by intramuscular injection in the deltoid region of the arm.
Outcomes
Primary Outcome Measures
Incident Rates of Definite Pulmonary Tuberculosis (TB) Disease, Not Associated With HIV-infection, Meeting the Case Definition 1
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.
Secondary Outcome Measures
Incident Rates of Definite Xpert MTB/Rif Positive Pulmonary TB Disease, Not Associated With HIV-infection, Meeting the Case Definition 2
The incidence rate of definite Xpert MTB/Rif positive pulmonary TB disease, expressed in terms of 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 2 = 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. *Clinical suspicion of pulmonary TB was defined as a subject presenting with one 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.
Incident Rates of Definite Pulmonary TB Disease, Not Associated With HIV-infection Meeting the Case Definition 3
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 3 = 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.*Clinical suspicion of pulmonary TB was defined as a subject presenting with one 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.
Incident Rates of Microbiological Pulmonary TB Disease, Meeting the Case Definition 4
The incidence rate of Microbiological 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 4 = 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.*Clinical suspicion of pulmonary TB was defined as a subject presenting with one 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.
Incidence Rates of Clinical TB Disease, Meeting the Case Definition 5
The incidence rate of Clinical 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 5 = a subject for whom a clinician has diagnosed TB disease and has decided to treat the patient with TB treatment.
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.
Number of Subjects With Any 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.
Number of Subjects With Any Solicited Local AEs in the Safety and Immune Sub-cohort
Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Any redness/swelling symptom was scored as injection site redness/swelling with a diameter equal or larger than (≥) 20 millimeters (mm).
Number of Subjects With Any Solicited General AEs in the Safety and Immune Sub-cohort
Assessed solicited general symptoms were fatigue, fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)], respiratory symptoms (including cough, blood in sputum, purulent sputum, shortness of breath or difficulties breathing, chest wall pain) headache, malaise and myalgia. Any = occurrence of the symptom regardless of intensity grade and relation to vaccination.
Number of Subjects With Any Potential Immune-mediated Diseases (pIMDs)
Potential immune-mediated diseases (pIMDs) are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.
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
Abnormal laboratory values include haematological abnormalities (haemoglobin level, white blood cells and platelets) and biochemical abnormalities (alanine aminotransferase, aspartate aminotransferase and creatinine). Grading was defined based on the Food and Drug Administration [FDA], 2007. Guidance for Industry, Toxicity Grading Scale for Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. Alanine Aminotransferase = ALA; Aspartate Aminotransferase = ASP; Creatinine = CREA; Hemoglobin (Change from baseline) = HEM (baseline); Hemoglobin (decrease) = HEM (decrease); Leukocytes (White Blood Cells) (Decrease) = WBC (decrease); Leukocytes (White Blood Cells) (Increase) = WBC (increase); Platelets = PLA; Total Bilirubin = BIL.
Desciptive Statistics of the Frequency of M72-specific CD4+ T-cells Expressing Any Combination of Immune Markers in the Safety and Immune Sub-cohort
The frequency of M72-specific CD4 + T-cells per million cells were identified after in vitro stimulation expressing any combination of immune markers ( Interleukin-2 (IL-2), cluster of differentiation 40-ligand (CD40-L), tumor necrosis factor alpha (TNF-) and interferon-gamma (IFN-) after background subtraction for each treatment group.
Desciptive Statistics of the Frequency of M72-specific CD8+ T-cells Expressing Any Combination of Immune Markers in the Safety and Immune Sub-cohort
The frequency of M72-specific CD8 + T-cells per million cells were identified after in vitro stimulation expressing any combination of immune markers ( Interleukin-2 (IL-2), cluster of differentiation 40-ligand (CD40-L), tumor necrosis factor alpha (TNF-) and interferon-gamma (IFN-) after background subtraction for each treatment group.
M72-specific Antibody Concentrations as Measured by Enzyme Linked Immuno Sorbent Assay (ELISA) in the Safety and Immune Sub-cohort
Mycobacterium tuberculosis M72-specific antibody geometric mean concentrations (GMCs) with exact 95% Confidence Interval (CI) were measured by Enzyme Linked Immuno Sorbent Assay (ELISA) and expressed in ELISA unit per milliliter (EU/mL). The cut-off of the assay was 2.8 EU/mL. The Geometric Mean Concentration (GMC) calculations were performed by taking the anti-log of the mean of the log10 concentration transformations. For descriptive statistics purposes only, antibody concentrations below the cut-off value of the assay was given an arbitrary value of half the cut-off value for the purpose of GMC calculation.
Number of Seropositive Subjects for M72 Antibodies Measured by ELISA in the Safety and Immune Sub-cohort
A seronegative subject was a subject whose antibody concentration was below 2.8 EU/mL, while a seropositive subject was a subject whose antibody concentration was greater than or equal to 2.8 EU/mL.
Full Information
NCT ID
NCT01755598
First Posted
December 19, 2012
Last Updated
November 12, 2019
Sponsor
GlaxoSmithKline
Collaborators
Aeras
1. Study Identification
Unique Protocol Identification Number
NCT01755598
Brief Title
Study to Evaluate the Efficacy of GlaxoSmithKline (GSK) Biologicals' Candidate Tuberculosis (TB) Vaccine in Adults
Official Title
Efficacy of GSK Biologicals' Candidate Tuberculosis (TB) Vaccine GSK 692342 Against TB Disease, in Adults Living in a TB Endemic Region
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
August 19, 2014 (Actual)
Primary Completion Date
November 16, 2018 (Actual)
Study Completion Date
November 16, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
Collaborators
Aeras
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
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.
Detailed Description
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.
• Fifth case definition: A subject for whom a clinician has diagnosed TB disease and has decided to treat the patient with TB treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis, Tuberculosis Vaccines
Keywords
Positive Interferon-γ release assay, Efficacy, Adults, Tuberculosis vaccine, Endemic region
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
3575 (Actual)
8. Arms, Groups, and Interventions
Arm Title
M72AS01 Group
Arm Type
Experimental
Arm Description
Subjects, between, and including, 18 and 50 years of age, who received 2 doses of M72/AS01E according to random assignment, one month apart (Day 0 and Day 30) by intramuscular injection in the deltoid region of the arm.
Arm Title
Control group
Arm Type
Placebo Comparator
Arm Description
Subjects, between, and including,18 and 50 years of age, who received 2 doses of Placebo according to random assignment, one month apart (Day 0 and Day 30) by intramuscular injection in the deltoid region of the arm.
Intervention Type
Biological
Intervention Name(s)
GSK Biologicals' investigational TB vaccine (GSK692342)
Intervention Description
2 doses administered intramuscularly in the deltoid region of the arm.
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
2 doses administered intramuscularly in the deltoid region of the arm.
Primary Outcome Measure Information:
Title
Incident Rates of Definite Pulmonary Tuberculosis (TB) Disease, Not Associated With HIV-infection, Meeting the Case Definition 1
Description
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.
Time Frame
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
Secondary Outcome Measure Information:
Title
Incident Rates of Definite Xpert MTB/Rif Positive Pulmonary TB Disease, Not Associated With HIV-infection, Meeting the Case Definition 2
Description
The incidence rate of definite Xpert MTB/Rif positive pulmonary TB disease, expressed in terms of 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 2 = 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. *Clinical suspicion of pulmonary TB was defined as a subject presenting with one 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.
Time Frame
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
Title
Incident Rates of Definite Pulmonary TB Disease, Not Associated With HIV-infection Meeting the Case Definition 3
Description
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 3 = 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.*Clinical suspicion of pulmonary TB was defined as a subject presenting with one 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.
Time Frame
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
Title
Incident Rates of Microbiological Pulmonary TB Disease, Meeting the Case Definition 4
Description
The incidence rate of Microbiological 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 4 = 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.*Clinical suspicion of pulmonary TB was defined as a subject presenting with one 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.
Time Frame
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
Title
Incidence Rates of Clinical TB Disease, Meeting the Case Definition 5
Description
The incidence rate of Clinical 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 5 = a subject for whom a clinician has diagnosed TB disease and has decided to treat the patient with TB treatment.
Time Frame
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
Title
Number of Subjects With Serious Adverse Events (SAEs).
Description
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.
Time Frame
From Day 0 up to Year 3 (during the entire study period)
Title
Number of Subjects With Any 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.
Time Frame
During the 30-day follow-up period following vaccination, across doses (i.e. day of vaccination and 29 subsequent days after each vaccine dose)
Title
Number of Subjects With Any Solicited Local AEs in the Safety and Immune Sub-cohort
Description
Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Any redness/swelling symptom was scored as injection site redness/swelling with a diameter equal or larger than (≥) 20 millimeters (mm).
Time Frame
During the 7-day follow-up period (i.e. day of vaccination and 6 subsequent days) after each vaccine dose
Title
Number of Subjects With Any Solicited General AEs in the Safety and Immune Sub-cohort
Description
Assessed solicited general symptoms were fatigue, fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)], respiratory symptoms (including cough, blood in sputum, purulent sputum, shortness of breath or difficulties breathing, chest wall pain) headache, malaise and myalgia. Any = occurrence of the symptom regardless of intensity grade and relation to vaccination.
Time Frame
During the 7-day follow-up period (i.e.: day of vaccination and 6 subsequent days) after each vaccine dose
Title
Number of Subjects With Any Potential Immune-mediated Diseases (pIMDs)
Description
Potential immune-mediated diseases (pIMDs) are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.
Time Frame
From Day 0 to 6 months post-dose 2 (i.e. at Month 7)
Title
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
Description
Abnormal laboratory values include haematological abnormalities (haemoglobin level, white blood cells and platelets) and biochemical abnormalities (alanine aminotransferase, aspartate aminotransferase and creatinine). Grading was defined based on the Food and Drug Administration [FDA], 2007. Guidance for Industry, Toxicity Grading Scale for Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. Alanine Aminotransferase = ALA; Aspartate Aminotransferase = ASP; Creatinine = CREA; Hemoglobin (Change from baseline) = HEM (baseline); Hemoglobin (decrease) = HEM (decrease); Leukocytes (White Blood Cells) (Decrease) = WBC (decrease); Leukocytes (White Blood Cells) (Increase) = WBC (increase); Platelets = PLA; Total Bilirubin = BIL.
Time Frame
Days 0, 7, 30 and 37
Title
Desciptive Statistics of the Frequency of M72-specific CD4+ T-cells Expressing Any Combination of Immune Markers in the Safety and Immune Sub-cohort
Description
The frequency of M72-specific CD4 + T-cells per million cells were identified after in vitro stimulation expressing any combination of immune markers ( Interleukin-2 (IL-2), cluster of differentiation 40-ligand (CD40-L), tumor necrosis factor alpha (TNF-) and interferon-gamma (IFN-) after background subtraction for each treatment group.
Time Frame
Prior to dose 1 (Day 0) and post-dose 2 (Day 60, Year 1, Year 2 and Year 3)
Title
Desciptive Statistics of the Frequency of M72-specific CD8+ T-cells Expressing Any Combination of Immune Markers in the Safety and Immune Sub-cohort
Description
The frequency of M72-specific CD8 + T-cells per million cells were identified after in vitro stimulation expressing any combination of immune markers ( Interleukin-2 (IL-2), cluster of differentiation 40-ligand (CD40-L), tumor necrosis factor alpha (TNF-) and interferon-gamma (IFN-) after background subtraction for each treatment group.
Time Frame
Prior to dose 1 (Day 0) and post-dose 2 (Day 60, Year 1, Year 2 and Year 3)
Title
M72-specific Antibody Concentrations as Measured by Enzyme Linked Immuno Sorbent Assay (ELISA) in the Safety and Immune Sub-cohort
Description
Mycobacterium tuberculosis M72-specific antibody geometric mean concentrations (GMCs) with exact 95% Confidence Interval (CI) were measured by Enzyme Linked Immuno Sorbent Assay (ELISA) and expressed in ELISA unit per milliliter (EU/mL). The cut-off of the assay was 2.8 EU/mL. The Geometric Mean Concentration (GMC) calculations were performed by taking the anti-log of the mean of the log10 concentration transformations. For descriptive statistics purposes only, antibody concentrations below the cut-off value of the assay was given an arbitrary value of half the cut-off value for the purpose of GMC calculation.
Time Frame
Prior to dose 1 (Day 0) and post-dose 2 (Day 60, Year 1, Year 2 and Year 3)
Title
Number of Seropositive Subjects for M72 Antibodies Measured by ELISA in the Safety and Immune Sub-cohort
Description
A seronegative subject was a subject whose antibody concentration was below 2.8 EU/mL, while a seropositive subject was a subject whose antibody concentration was greater than or equal to 2.8 EU/mL.
Time Frame
Prior to dose 1 (Day 0) and post-dose 2 (Day 60, Year 1, Year 2 and Year 3)
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, 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.
Exclusion Criteria:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Kisumu
Country
Kenya
Facility Name
GSK Investigational Site
City
Pretoria
State/Province
Gauteng
ZIP/Postal Code
0152
Country
South Africa
Facility Name
GSK Investigational Site
City
Soweto
State/Province
Gauteng
ZIP/Postal Code
2013
Country
South Africa
Facility Name
GSK Investigational Site
City
Klerksdorp
State/Province
North-West
ZIP/Postal Code
2571
Country
South Africa
Facility Name
GSK Investigational Site
City
Western Cape
State/Province
Western Province
Country
South Africa
Facility Name
GSK Investigational Site
City
Worcester
State/Province
Western Province
ZIP/Postal Code
6850
Country
South Africa
Facility Name
GSK Investigational Site
City
Cape Town
ZIP/Postal Code
7530
Country
South Africa
Facility Name
GSK Investigational Site
City
Cape Town
ZIP/Postal Code
7925
Country
South Africa
Facility Name
GSK Investigational Site
City
Lusaka
Country
Zambia
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
IPD is available via the Clinical Study Data Request site (click on the link provided below)
IPD Sharing Time Frame
IPD is available via the Clinical Study Data Request site (click on the link provided below)
IPD Sharing Access Criteria
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
IPD Sharing URL
https://clinicalstudydatarequest.com/Posting.aspx?ID=20104
Citations:
PubMed Identifier
31661198
Citation
Tait DR, Hatherill M, Van Der Meeren O, Ginsberg AM, Van Brakel E, Salaun B, Scriba TJ, Akite EJ, Ayles HM, Bollaerts A, Demoitie MA, Diacon A, Evans TG, Gillard P, Hellstrom E, Innes JC, Lempicki M, Malahleha M, Martinson N, Mesia Vela D, Muyoyeta M, Nduba V, Pascal TG, Tameris M, Thienemann F, Wilkinson RJ, Roman F. Final Analysis of a Trial of M72/AS01E Vaccine to Prevent Tuberculosis. N Engl J Med. 2019 Dec 19;381(25):2429-2439. doi: 10.1056/NEJMoa1909953. Epub 2019 Oct 29.
Results Reference
derived
PubMed Identifier
30280651
Citation
Van Der Meeren O, Hatherill M, Nduba V, Wilkinson RJ, Muyoyeta M, Van Brakel E, Ayles HM, Henostroza G, Thienemann F, Scriba TJ, Diacon A, Blatner GL, Demoitie MA, Tameris M, Malahleha M, Innes JC, Hellstrom E, Martinson N, Singh T, Akite EJ, Khatoon Azam A, Bollaerts A, Ginsberg AM, Evans TG, Gillard P, Tait DR. Phase 2b Controlled Trial of M72/AS01E Vaccine to Prevent Tuberculosis. N Engl J Med. 2018 Oct 25;379(17):1621-1634. doi: 10.1056/NEJMoa1803484. Epub 2018 Sep 25.
Results Reference
derived
Learn more about this trial
Study to Evaluate the Efficacy of GlaxoSmithKline (GSK) Biologicals' Candidate Tuberculosis (TB) Vaccine in Adults
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