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Study to Evaluate the Efficacy of GlaxoSmithKline (GSK) Biologicals' Candidate Tuberculosis (TB) Vaccine in Adults

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ClinicalTrials.gov Identifier: NCT01755598
Recruitment Status : Completed
First Posted : December 24, 2012
Results First Posted : December 3, 2019
Last Update Posted : December 3, 2019
Sponsor:
Collaborator:
Aeras
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Conditions Tuberculosis
Tuberculosis Vaccines
Interventions Biological: GSK Biologicals' investigational TB vaccine (GSK692342)
Biological: Placebo
Enrollment 3575
Recruitment Details Out of 3575 subjects enrolled in the study, 2 subjects did not get any vaccination and therefore were not included in any analysis.
Pre-assignment Details  
Arm/Group Title M72AS01 Group Control Group
Hide Arm/Group 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.
Period Title: Overall Study
Started 1786 1787
Completed 1521 1504
Not Completed 265 283
Reason Not Completed
Other             109             109
Lost to Follow-up             32             43
Migrated/moved from study area             76             65
Withdrawal by Subject             22             31
Protocol Violation             7             7
Adverse Event             19             28
Arm/Group Title M72AS01 Group Control Group Total
Hide Arm/Group 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. Total of all reporting groups
Overall Number of Baseline Participants 1786 1787 3573
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1786 participants 1787 participants 3573 participants
28.9  (8.3) 28.9  (8.3) 28.9  (8.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1786 participants 1787 participants 3573 participants
Female
763
  42.7%
766
  42.9%
1529
  42.8%
Male
1023
  57.3%
1021
  57.1%
2044
  57.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1786 participants 1787 participants 3573 participants
African Heritage / African American
1346
  75.4%
1329
  74.4%
2675
  74.9%
Other, Not Specified
440
  24.6%
458
  25.6%
898
  25.1%
1.Primary Outcome
Title Incident Rates of Definite Pulmonary Tuberculosis (TB) Disease, Not Associated With HIV-infection, Meeting the Case Definition 1
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the According-to-Protocol cohort for efficacy which included all subjects who received all vaccinations according to protocol procedures within specified intervals that contributed time at risk in the follow-up period starting one month post dose 2 (Day 60).
Arm/Group Title M72AS01 Group Control Group
Hide Arm/Group 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.
Overall Number of Participants Analyzed 1626 1663
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: cases per 100 person-years
0.3
(0.2 to 0.5)
0.6
(0.4 to 0.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection M72AS01 Group, Control Group
Comments To evaluate the protective efficacy of two doses of the M72/AS01E candidate vaccine against Definite pulmonary TB disease not associated with HIV-infection, meeting the case definition 1, as compared to placebo.
Type of Statistical Test Other
Comments Vaccine efficacy (VE) has been estimated from a Cox proportional hazard regression model (VE=1-hazard ratio) and 90% confidence intervals (CIs) and Wald p-value has been derived. The lower limit of the 90% two-sided CI for the VE against first occurrence of Definite pulmonary TB disease not associated with HIV-infection, meeting the case definition 1, is to be above 0%.
Statistical Test of Hypothesis P-Value 0.0430
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine efficacy rate
Estimated Value 49.7
Confidence Interval (2-Sided) 90%
12.1 to 71.2
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Incident Rates of Definite Xpert MTB/Rif Positive Pulmonary TB Disease, Not Associated With HIV-infection, Meeting the Case Definition 2
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the According-to-Protocol cohort for efficacy which included all subjects who received all vaccinations according to protocol procedures within specified intervals that contributed time at risk in the follow-up period starting one month post dose 2 (Day 60).
Arm/Group Title M72AS01 Group Control Group
Hide Arm/Group 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.
Overall Number of Participants Analyzed 1626 1663
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: cases per 100 person-years
0.181
(0.101 to 0.323)
0.470
(0.328 to 0.673)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection M72AS01 Group, Control Group
Comments To evaluate the protective efficacy of two doses of the M72/AS01E candidate vaccine against Definite Xpert MTB/Rif positive pulmonary TB disease not associated with HIV-infection, meeting the case definition 2, as compared to placebo.
Type of Statistical Test Other
Comments Vaccine efficacy (VE) has been estimated from a Cox proportional hazard regression model (VE=1-hazard ratio) and 90% confidence intervals (CIs) and Wald p-value has been derived. If the primary objective is met, this secondary objective is to be analysed using the following success criterion: The lower limit of the 90% two-sided CI for the VE against first occurrence of Definite pulmonary TB disease not associated with HIV infection, meeting the case definition 2, is to be above 0%.
Statistical Test of Hypothesis P-Value 0.0210
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine efficacy rate
Estimated Value 61.670
Confidence Interval (2-Sided) 90%
24.084 to 80.647
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Incident Rates of Definite Pulmonary TB Disease, Not Associated With HIV-infection Meeting the Case Definition 3
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the According-to-Protocol cohort for efficacy which included all subjects who received all vaccinations according to protocol procedures within specified intervals that contributed time at risk in the follow-up period starting one month post dose 2 (Day 60).
Arm/Group Title M72AS01 Group Control Group
Hide Arm/Group 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.
Overall Number of Participants Analyzed 1626 1663
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: cases per 100 person-years
0.429
(0.294 to 0.626)
0.672
(0.498 to 0.908)
4.Secondary Outcome
Title Incident Rates of Microbiological Pulmonary TB Disease, Meeting the Case Definition 4
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the According-to-Protocol cohort for efficacy which included all subjects who received all vaccinations according to protocol procedures within specified intervals that contributed time at risk in the follow-up period starting one month post dose 2 (Day 60).
Arm/Group Title M72AS01 Group Control Group
Hide Arm/Group 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.
Overall Number of Participants Analyzed 1626 1663
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: cases per 100 person-years
0.429
(0.294 to 0.626)
0.717
(0.536 to 0.959)
5.Secondary Outcome
Title Incidence Rates of Clinical TB Disease, Meeting the Case Definition 5
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the According-to-Protocol cohort for efficacy which included all subjects who received all vaccinations according to protocol procedures within specified intervals that contributed time at risk in the follow-up period starting one month post dose 2 (Day 60).
Arm/Group Title M72AS01 Group Control Group
Hide Arm/Group 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.
Overall Number of Participants Analyzed 1626 1663
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: cases per 100 person-years
0.586
(0.425 to 0.810)
0.850
(0.651 to 1.109)
6.Secondary Outcome
Title Number of Subjects With Serious Adverse Events (SAEs).
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Total Vaccinated cohort which included all vaccinated subjects with at least one dose administered.
Arm/Group Title M72AS01 Group Control Group
Hide Arm/Group 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.
Overall Number of Participants Analyzed 1786 1787
Measure Type: Count of Participants
Unit of Measure: Participants
51
   2.9%
62
   3.5%
7.Secondary Outcome
Title Number of Subjects With Any Unsolicited Adverse Events (AEs).
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Total Vaccinated cohort which included all vaccinated subjects with at least one dose administered.
Arm/Group Title M72AS01 Group Control Group
Hide Arm/Group 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.
Overall Number of Participants Analyzed 1786 1787
Measure Type: Count of Participants
Unit of Measure: Participants
1207
  67.6%
816
  45.7%
8.Secondary Outcome
Title Number of Subjects With Any Solicited Local AEs in the Safety and Immune Sub-cohort
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the "safety and immunogenicity" sub-cohort (i.e. about 150 subjects enrolled in each group and from 2 of the 3 countries [the third country study start was delayed as awaiting regulatory approval]) which included subjects with at least 1 vaccination dose documented.
Arm/Group Title M72AS01 Group Control Group
Hide Arm/Group 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.
Overall Number of Participants Analyzed 148 151
Measure Type: Count of Participants
Unit of Measure: Participants
Any Pain after Dose 1 Number Analyzed 148 participants 151 participants
111
  75.0%
48
  31.8%
Any Redness after Dose 1 Number Analyzed 148 participants 151 participants
12
   8.1%
0
   0.0%
Any Swelling after Dose 1 Number Analyzed 148 participants 151 participants
25
  16.9%
1
   0.7%
Any Pain after Dose 2 Number Analyzed 130 participants 141 participants
86
  66.2%
22
  15.6%
Any Redness after Dose 2 Number Analyzed 130 participants 141 participants
5
   3.8%
2
   1.4%
Any Swelling after Dose 2 Number Analyzed 130 participants 141 participants
12
   9.2%
2
   1.4%
9.Secondary Outcome
Title Number of Subjects With Any Solicited General AEs in the Safety and Immune Sub-cohort
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the "safety and immunogenicity" sub-cohort (i.e. about 150 subjects enrolled in each group and from 2 of the 3 countries [the third country study start was delayed as awaiting regulatory approval]) which included subjects with at least 1 vaccination dose documented.
Arm/Group Title M72AS01 Group Control Group
Hide Arm/Group 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.
Overall Number of Participants Analyzed 148 151
Measure Type: Count of Participants
Unit of Measure: Participants
Any Fatigue after Dose 1 Number Analyzed 148 participants 151 participants
91
  61.5%
63
  41.7%
Any Headache after Dose 1 Number Analyzed 148 participants 151 participants
81
  54.7%
60
  39.7%
Any Malaise after Dose 1 Number Analyzed 148 participants 151 participants
68
  45.9%
29
  19.2%
Any Myalgia after Dose 1 Number Analyzed 148 participants 151 participants
75
  50.7%
34
  22.5%
Any Respiratory symptoms after Dose 1 Number Analyzed 148 participants 151 participants
23
  15.5%
13
   8.6%
Any Fever after Dose 1 Number Analyzed 148 participants 151 participants
33
  22.3%
16
  10.6%
Any Fatigue after Dose 2 Number Analyzed 130 participants 141 participants
70
  53.8%
31
  22.0%
Any Headache after Dose 2 Number Analyzed 130 participants 141 participants
75
  57.7%
39
  27.7%
Any Malaise after Dose 2 Number Analyzed 130 participants 141 participants
57
  43.8%
21
  14.9%
Any Myalgia after Dose 2 Number Analyzed 130 participants 141 participants
55
  42.3%
21
  14.9%
Any Respiratory symptoms after Dose 2 Number Analyzed 130 participants 141 participants
14
  10.8%
5
   3.5%
Any Fever after Dose 2 Number Analyzed 130 participants 141 participants
37
  28.5%
10
   7.1%
10.Secondary Outcome
Title Number of Subjects With Any Potential Immune-mediated Diseases (pIMDs)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Total Vaccinated cohort which included all vaccinated subjects with at least one dose administered.
Arm/Group Title M72AS01 Group Control Group
Hide Arm/Group 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.
Overall Number of Participants Analyzed 1786 1787
Measure Type: Count of Participants
Unit of Measure: Participants
2
   0.1%
6
   0.3%
11.Secondary Outcome
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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the "safety and immunogenicity" sub-cohort (i.e. about 150 subjects enrolled in each group and from 2 of the 3 countries [the third country study start was delayed as awaiting regulatory approval]) which included subjects with at least 1 laboratory value documented.
Arm/Group Title M72AS01 Group Control Group
Hide Arm/Group 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.
Overall Number of Participants Analyzed 149 151
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 2 ALA at Day 0 Number Analyzed 149 participants 151 participants
0
   0.0%
0
   0.0%
Grade 3 ALA at Day 0 Number Analyzed 149 participants 151 participants
0
   0.0%
0
   0.0%
Grade 4 ALA at Day 0 Number Analyzed 149 participants 151 participants
0
   0.0%
0
   0.0%
Grade 2 ALA at Day 7 Number Analyzed 149 participants 146 participants
0
   0.0%
0
   0.0%
Grade 3 ALA at Day 7 Number Analyzed 149 participants 146 participants
0
   0.0%
0
   0.0%
Grade 4 ALA at Day 7 Number Analyzed 149 participants 146 participants
0
   0.0%
0
   0.0%
Grade 2 ALA at Day 30 Number Analyzed 139 participants 151 participants
0
   0.0%
0
   0.0%
Grade 3 ALA at Day 30 Number Analyzed 139 participants 151 participants
0
   0.0%
0
   0.0%
Grade 4 ALA at Day 30 Number Analyzed 139 participants 151 participants
0
   0.0%
0
   0.0%
Grade 2 ALA at Day 37 Number Analyzed 122 participants 136 participants
0
   0.0%
0
   0.0%
Grade 3 ALA at Day 37 Number Analyzed 122 participants 136 participants
0
   0.0%
0
   0.0%
Grade 4 ALA at Day 37 Number Analyzed 122 participants 136 participants
0
   0.0%
0
   0.0%
Grade 2 ASP at Day 0 Number Analyzed 149 participants 151 participants
1
   0.7%
0
   0.0%
Grade 3 ASP at Day 0 Number Analyzed 149 participants 151 participants
0
   0.0%
0
   0.0%
Grade 4 ASP at Day 0 Number Analyzed 149 participants 151 participants
0
   0.0%
0
   0.0%
Grade 2 ASP at Day 7 Number Analyzed 149 participants 146 participants
1
   0.7%
0
   0.0%
Grade 3 ASP at Day 7 Number Analyzed 149 participants 146 participants
0
   0.0%
0
   0.0%
Grade 4 ASP at Day 7 Number Analyzed 149 participants 146 participants
0
   0.0%
0
   0.0%
Grade 2 ASP at Day 30 Number Analyzed 139 participants 151 participants
0
   0.0%
0
   0.0%
Grade 3 ASP at Day 30 Number Analyzed 139 participants 151 participants
0
   0.0%
0
   0.0%
Grade 4 ASP at Day 30 Number Analyzed 139 participants 151 participants
0
   0.0%
0
   0.0%
Grade 2 ASP at Day 37 Number Analyzed 122 participants 136 participants
0
   0.0%
0
   0.0%
Grade 3 ASP at Day 37 Number Analyzed 122 participants 136 participants
1
   0.8%
0
   0.0%
Grade 4 ASP at Day 37 Number Analyzed 122 participants 136 participants
0
   0.0%
0
   0.0%
Grade 2 CREA at Day 0 Number Analyzed 149 participants 151 participants
0
   0.0%
0
   0.0%
Grade 3 CREA at Day 0 Number Analyzed 149 participants 151 participants
0
   0.0%
0
   0.0%
Grade 4 CREA at Day 0 Number Analyzed 149 participants 151 participants
0
   0.0%
0
   0.0%
Grade 2 CREA at Day 7 Number Analyzed 149 participants 146 participants
0
   0.0%
0
   0.0%
Grade 3 CREA at Day 7 Number Analyzed 149 participants 146 participants
0
   0.0%
0
   0.0%
Grade 4 CREA at Day 7 Number Analyzed 149 participants 146 participants
0
   0.0%
0
   0.0%
Grade 2 CREA at Day 30 Number Analyzed 139 participants 151 participants
0
   0.0%
0
   0.0%
Grade 3 CREA at Day 30 Number Analyzed 139 participants 151 participants
0
   0.0%
0
   0.0%
Grade 4 CREA at Day 30 Number Analyzed 139 participants 151 participants
0
   0.0%
0
   0.0%
Grade 2 CREA at Day 37 Number Analyzed 122 participants 136 participants
0
   0.0%
0
   0.0%
Grade 3 CREA at Day 37 Number Analyzed 122 participants 136 participants
0
   0.0%
0
   0.0%
Grade 4 CREA at Day 37 Number Analyzed 122 participants 136 participants
0
   0.0%
0
   0.0%
Grade 2 HEM (baseline) at Day 0 Number Analyzed 149 participants 151 participants
0
   0.0%
0
   0.0%
Grade 3 HEM (baseline) at Day 0 Number Analyzed 149 participants 151 participants
0
   0.0%
0
   0.0%
Grade 4 HEM (baseline) at Day 0 Number Analyzed 149 participants 151 participants
0
   0.0%
0
   0.0%
Grade 2 HEM (baseline) at Day 7 Number Analyzed 149 participants 146 participants
1
   0.7%
5
   3.4%
Grade 3 HEM (baseline) at Day 7 Number Analyzed 149 participants 146 participants
0
   0.0%
0
   0.0%
Grade 4 HEM (baseline) at Day 7 Number Analyzed 149 participants 146 participants
0
   0.0%
0
   0.0%
Grade 2 HEM (baseline) at Day 30 Number Analyzed 139 participants 151 participants
2
   1.4%
2
   1.3%
Grade 3 HEM (baseline) at Day 30 Number Analyzed 139 participants 151 participants
0
   0.0%
0
   0.0%
Grade 4 HEM (baseline) at Day 30 Number Analyzed 139 participants 151 participants
0
   0.0%
0
   0.0%
Grade 2 HEM (baseline) at Day 37 Number Analyzed 122 participants 136 participants
2
   1.6%
0
   0.0%
Grade 3 HEM (baseline) at Day 37 Number Analyzed 122 participants 136 participants
1
   0.8%
0
   0.0%
Grade 4 HEM (baseline) at Day 37 Number Analyzed 122 participants 136 participants
0
   0.0%
0
   0.0%
Grade 2 HEM (decrease) at Day 0 Number Analyzed 149 participants 151 participants
5
   3.4%
5
   3.3%
Grade 3 HEM (decrease) at Day 0 Number Analyzed 149 participants 151 participants
2
   1.3%
1
   0.7%
Grade 4 HEM (decrease) at Day 0 Number Analyzed 149 participants 151 participants
1
   0.7%
0
   0.0%
Grade 2 HEM (decrease) at Day 7 Number Analyzed 149 participants 146 participants
10
   6.7%
5
   3.4%
Grade 3 HEM (decrease) at Day 7 Number Analyzed 149 participants 146 participants
2
   1.3%
2
   1.4%
Grade 4 HEM (decrease) at Day 7 Number Analyzed 149 participants 146 participants
0
   0.0%
0
   0.0%
Grade 2 HEM (decrease) at Day 30 Number Analyzed 139 participants 151 participants
5
   3.6%
4
   2.6%
Grade 3 HEM (decrease) at Day 30 Number Analyzed 139 participants 151 participants
2
   1.4%
1
   0.7%
Grade 4 HEM (decrease) at Day 30 Number Analyzed 139 participants 151 participants
0
   0.0%
0
   0.0%
Grade 2 HEM (decrease) at Day 37 Number Analyzed 122 participants 136 participants
4
   3.3%
4
   2.9%
Grade 3 HEM (decrease) at Day 37 Number Analyzed 122 participants 136 participants
1
   0.8%
0
   0.0%
Grade 4 HEM (decrease) at Day 37 Number Analyzed 122 participants 136 participants
0
   0.0%
0
   0.0%
Grade 2 WBC (decrease) at Day 0 Number Analyzed 149 participants 151 participants
0
   0.0%
0
   0.0%
Grade 3 WBC (decrease) at Day 0 Number Analyzed 149 participants 151 participants
0
   0.0%
0
   0.0%
Grade 4 WBC (decrease) at Day 0 Number Analyzed 149 participants 151 participants
0
   0.0%
0
   0.0%
Grade 2 WBC (decrease) at Day 7 Number Analyzed 149 participants 146 participants
0
   0.0%
0
   0.0%
Grade 3 WBC (decrease) at Day 7 Number Analyzed 149 participants 146 participants
0
   0.0%
0
   0.0%
Grade 4 WBC (decrease) at Day 7 Number Analyzed 149 participants 146 participants
0
   0.0%
0
   0.0%
Grade 2 WBC (decrease) at Day 30 Number Analyzed 139 participants 151 participants
0
   0.0%
0
   0.0%
Grade 3 WBC (decrease) at Day 30 Number Analyzed 139 participants 151 participants
0
   0.0%
0
   0.0%
Grade 4 WBC (decrease) at Day 30 Number Analyzed 139 participants 151 participants
0
   0.0%
0
   0.0%
Grade 2 WBC (decrease) at Day 37 Number Analyzed 122 participants 136 participants
0
   0.0%
0
   0.0%
Grade 3 WBC (decrease) at Day 37 Number Analyzed 122 participants 136 participants
0
   0.0%
0
   0.0%
Grade 4 WBC (decrease) at Day 37 Number Analyzed 122 participants 136 participants
0
   0.0%
0
   0.0%
Grade 2 WBC (increase) at Day 0 Number Analyzed 149 participants 151 participants
0
   0.0%
0
   0.0%
Grade 3 WBC (increase) at Day 0 Number Analyzed 149 participants 151 participants
0
   0.0%
0
   0.0%
Grade 4 WBC (increase) at Day 0 Number Analyzed 149 participants 151 participants
0
   0.0%
0
   0.0%
Grade 2 WBC (increase) at Day 7 Number Analyzed 149 participants 146 participants
0
   0.0%
0
   0.0%
Grade 3 WBC (increase) at Day 7 Number Analyzed 149 participants 146 participants
0
   0.0%
0
   0.0%
Grade 4 WBC (increase) at Day 7 Number Analyzed 149 participants 146 participants
0
   0.0%
0
   0.0%
Grade 2 WBC (increase) at Day 30 Number Analyzed 139 participants 151 participants
0
   0.0%
0
   0.0%
Grade 3 WBC (increase) at Day 30 Number Analyzed 139 participants 151 participants
0
   0.0%
0
   0.0%
Grade 4 WBC (increase) at Day 30 Number Analyzed 139 participants 151 participants
0
   0.0%
0
   0.0%
Grade 2 WBC (increase) at Day 37 Number Analyzed 122 participants 136 participants
0
   0.0%
0
   0.0%
Grade 3 WBC (increase) at Day 37 Number Analyzed 122 participants 136 participants
0
   0.0%
0
   0.0%
Grade 4 WBC (increase) at Day 37 Number Analyzed 122 participants 136 participants
0
   0.0%
0
   0.0%
Grade 2 PLA at Day 0 Number Analyzed 149 participants 151 participants
3
   2.0%
2
   1.3%
Grade 3 PLA at Day 0 Number Analyzed 149 participants 151 participants
4
   2.7%
0
   0.0%
Grade 4 PLA at Day 0 Number Analyzed 149 participants 151 participants
0
   0.0%
0
   0.0%
Grade 2 PLA at Day 7 Number Analyzed 149 participants 146 participants
0
   0.0%
1
   0.7%
Grade 3 PLA at Day 7 Number Analyzed 149 participants 146 participants
3
   2.0%
0
   0.0%
Grade 4 PLA at Day 7 Number Analyzed 149 participants 146 participants
0
   0.0%
0
   0.0%
Grade 2 PLA at Day 30 Number Analyzed 139 participants 151 participants
1
   0.7%
3
   2.0%
Grade 3 PLA at Day 30 Number Analyzed 139 participants 151 participants
3
   2.2%
1
   0.7%
Grade 4 PLA at Day 30 Number Analyzed 139 participants 151 participants
0
   0.0%
0
   0.0%
Grade 2 PLA at Day 37 Number Analyzed 122 participants 136 participants
1
   0.8%
1
   0.7%
Grade 3 PLA at Day 37 Number Analyzed 122 participants 136 participants
3
   2.5%
0
   0.0%
Grade 4 PLA at Day 37 Number Analyzed 122 participants 136 participants
0
   0.0%
0
   0.0%
Grade 2 BIL at Day 0 Number Analyzed 149 participants 151 participants
1
   0.7%
4
   2.6%
Grade 3 BIL at Day 0 Number Analyzed 149 participants 151 participants
0
   0.0%
0
   0.0%
Grade 4 BIL at Day 0 Number Analyzed 149 participants 151 participants
0
   0.0%
1
   0.7%
Grade 2 BIL at Day 7 Number Analyzed 149 participants 146 participants
0
   0.0%
1
   0.7%
Grade 3 BIL at Day 7 Number Analyzed 149 participants 146 participants
0
   0.0%
1
   0.7%
Grade 4 BIL at Day 7 Number Analyzed 149 participants 146 participants
0
   0.0%
1
   0.7%
Grade 2 BIL at Day 30 Number Analyzed 139 participants 151 participants
1
   0.7%
1
   0.7%
Grade 3 BIL at Day 30 Number Analyzed 139 participants 151 participants
1
   0.7%
1
   0.7%
Grade 4 BIL at Day 30 Number Analyzed 139 participants 151 participants
3
   2.2%
1
   0.7%
Grade 2 BIL at Day 37 Number Analyzed 122 participants 136 participants
1
   0.8%
2
   1.5%
Grade 3 BIL at Day 37 Number Analyzed 122 participants 136 participants
0
   0.0%
0
   0.0%
Grade 4 BIL at Day 37 Number Analyzed 122 participants 136 participants
0
   0.0%
0
   0.0%
12.Secondary Outcome
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
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the "safety and immunogenicity" sub-cohort (i.e. about 150 subjects enrolled in each group and from 2 of the 3 countries [the third country study start was delayed as awaiting regulatory approval]) which included subjects with at least 1 immune result documented.
Arm/Group Title M72AS01 Group Control Group
Hide Arm/Group 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.
Overall Number of Participants Analyzed 84 84
Median (Inter-Quartile Range)
Unit of Measure: T cells per million cells
CD4.CD40L(+)+IL2(+)+TNFa(+)+IFNg(+) at Day 0 Number Analyzed 71 participants 69 participants
1.0
(1.0 to 178.0)
28.0
(1.0 to 135.0)
CD4.CD40L(+)+IL2(+)+TNFa(+)+IFNg(+) at Day 60 Number Analyzed 51 participants 48 participants
1.0
(1.0 to 227.0)
1.0
(1.0 to 86.5)
CD4.CD40L(+)+IL2(+)+TNFa(+)+IFNg(+) at Year 1 Number Analyzed 84 participants 79 participants
300.5
(66.5 to 831.5)
53.0
(1.0 to 255.0)
CD4.CD40L(+)+IL2(+)+TNFa(+)+IFNg(+) at Year 2 Number Analyzed 76 participants 84 participants
1.0
(1.0 to 480.0)
1.0
(1.0 to 113.5)
CD4.CD40L(+)+IL2(+)+TNFa(+)+IFNg(+) at Year 3 Number Analyzed 54 participants 60 participants
670.5
(319.0 to 1320.0)
145.0
(39.0 to 349.5)
CD4.CD40L(+)+IL2(+)+TNFa(+)+IFNg(-) at Day 0 Number Analyzed 71 participants 69 participants
1.0
(1.0 to 55.0)
1.0
(1.0 to 21.0)
CD4.CD40L(+)+IL2(+)+TNFa(+)+IFNg(-) at Day 60 Number Analyzed 51 participants 48 participants
1.0
(1.0 to 254.0)
1.0
(1.0 to 28.0)
CD4.CD40L(+)+IL2(+)+TNFa(+)+IFNg(-) at Year 1 Number Analyzed 84 participants 79 participants
128.5
(26.0 to 281.0)
14.0
(1.0 to 48.0)
CD4.CD40L(+)+IL2(+)+TNFa(+)+IFNg(-) at Year 2 Number Analyzed 76 participants 84 participants
1.0
(1.0 to 140.5)
1.0
(1.0 to 34.5)
CD4.CD40L(+)+IL2(+)+TNFa(+)+IFNg(-) at Year 3 Number Analyzed 54 participants 60 participants
244.0
(127.0 to 356.0)
32.0
(1.0 to 77.5)
CD4.CD40L(+)+IL2(+)+TNFa(-)+IFNg(+) at Day 0 Number Analyzed 71 participants 69 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD4.CD40L(+)+IL2(+)+TNFa(-)+IFNg(+) at Day 60 Number Analyzed 51 participants 48 participants
1.0
(1.0 to 17.0)
1.0
(1.0 to 1.0)
CD4.CD40L(+)+IL2(+)+TNFa(-)+IFNg(+) at Year 1 Number Analyzed 84 participants 79 participants
1.0
(1.0 to 6.0)
1.0
(1.0 to 1.0)
CD4.CD40L(+)+IL2(+)+TNFa(-)+IFNg(+) at Year 2 Number Analyzed 76 participants 84 participants
1.0
(1.0 to 15.0)
1.0
(1.0 to 1.0)
CD4.CD40L(+)+IL2(+)+TNFa(-)+IFNg(+) at Year 3 Number Analyzed 54 participants 60 participants
1.5
(1.0 to 67.0)
1.0
(1.0 to 1.0)
CD4.CD40L(+)+IL2(+)+TNFa(-)+IFNg(-) at Day 0 Number Analyzed 71 participants 69 participants
1.0
(1.0 to 23.0)
1.0
(1.0 to 1.0)
CD4.CD40L(+)+IL2(+)+TNFa(-)+IFNg(-) at Day 60 Number Analyzed 51 participants 48 participants
1.0
(1.0 to 28.0)
1.0
(1.0 to 1.0)
CD4.CD40L(+)+IL2(+)+TNFa(-)+IFNg(-) at Year 1 Number Analyzed 84 participants 79 participants
1.0
(1.0 to 25.0)
1.0
(1.0 to 1.0)
CD4.CD40L(+)+IL2(+)+TNFa(-)+IFNg(-) at Year 2 Number Analyzed 76 participants 84 participants
1.0
(1.0 to 11.5)
1.0
(1.0 to 1.0)
CD4.CD40L(+)+IL2(+)+TNFa(-)+IFNg(-) at Year 3 Number Analyzed 54 participants 60 participants
1.0
(1.0 to 27.0)
1.0
(1.0 to 6.5)
CD4.CD40L(+)+IL2(-)+TNFa(+)+IFNg(+) at Day 0 Number Analyzed 71 participants 69 participants
1.0
(1.0 to 21.0)
1.0
(1.0 to 1.0)
CD4.CD40L(+)+IL2(-)+TNFa(+)+IFNg(+) at Day 60 Number Analyzed 51 participants 48 participants
1.0
(1.0 to 41.0)
1.0
(1.0 to 1.0)
CD4.CD40L(+)+IL2(-)+TNFa(+)+IFNg(+) at Year 1 Number Analyzed 84 participants 79 participants
1.0
(1.0 to 28.0)
1.0
(1.0 to 19.0)
CD4.CD40L(+)+IL2(-)+TNFa(+)+IFNg(+) at Year 2 Number Analyzed 76 participants 84 participants
1.0
(1.0 to 15.5)
1.0
(1.0 to 1.0)
CD4.CD40L(+)+IL2(-)+TNFa(+)+IFNg(+) at Year 3 Number Analyzed 54 participants 60 participants
32.0
(1.0 to 107.0)
1.0
(1.0 to 31.5)
CD4.CD40L(+)+IL2(-)+TNFa(+)+IFNg(-) at Day 0 Number Analyzed 71 participants 69 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD4.CD40L(+)+IL2(-)+TNFa(+)+IFNg(-) at Day 60 Number Analyzed 51 participants 48 participants
1.0
(1.0 to 6.0)
1.0
(1.0 to 1.0)
CD4.CD40L(+)+IL2(-)+TNFa(+)+IFNg(-) at Year 1 Number Analyzed 84 participants 79 participants
1.0
(1.0 to 19.5)
1.0
(1.0 to 1.0)
CD4.CD40L(+)+IL2(-)+TNFa(+)+IFNg(-) at Year 2 Number Analyzed 76 participants 84 participants
1.0
(1.0 to 13.0)
1.0
(1.0 to 1.0)
CD4.CD40L(+)+IL2(-)+TNFa(+)+IFNg(-) at Year 3 Number Analyzed 54 participants 60 participants
19.0
(1.0 to 49.0)
1.0
(1.0 to 13.0)
CD4.CD40L(+)+IL2(-)+TNFa(-)+IFNg(+) at Day 0 Number Analyzed 71 participants 69 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 5.0)
CD4.CD40L(+)+IL2(-)+TNFa(-)+IFNg(+) at Day 60 Number Analyzed 51 participants 48 participants
1.0
(1.0 to 15.0)
1.0
(1.0 to 1.0)
CD4.CD40L(+)+IL2(-)+TNFa(-)+IFNg(+) at Year 1 Number Analyzed 84 participants 79 participants
1.0
(1.0 to 15.0)
1.0
(1.0 to 13.0)
CD4.CD40L(+)+IL2(-)+TNFa(-)+IFNg(+) at Year 2 Number Analyzed 76 participants 79 participants
1.0
(1.0 to 13.0)
1.0
(1.0 to 13.0)
CD4.CD40L(+)+IL2(-)+TNFa(-)+IFNg(+) at Year 3 Number Analyzed 54 participants 60 participants
1.0
(1.0 to 24.0)
1.0
(1.0 to 21.0)
CD4.CD40L(+)+IL2(-)+TNFa(-)+IFNg(-) at Day 0 Number Analyzed 71 participants 69 participants
1.0
(1.0 to 138.0)
1.0
(1.0 to 114.0)
CD4.CD40L(+)+IL2(-)+TNFa(-)+IFNg(-) at Day 60 Number Analyzed 51 participants 48 participants
1.0
(1.0 to 169.0)
25.5
(1.0 to 158.0)
CD4.CD40L(+)+IL2(-)+TNFa(-)+IFNg(-) at Year 1 Number Analyzed 84 participants 79 participants
5.0
(1.0 to 45.0)
1.0
(1.0 to 36.0)
CD4.CD40L(+)+IL2(-)+TNFa(-)+IFNg(-) at Year 2 Number Analyzed 76 participants 84 participants
1.0
(1.0 to 30.0)
1.0
(1.0 to 74.5)
CD4.CD40L(+)+IL2(-)+TNFa(-)+IFNg(-) at Year 3 Number Analyzed 54 participants 60 participants
8.5
(1.0 to 128.0)
11.0
(1.0 to 117.0)
CD4.CD40L(-)+IL2(+)+TNFa(+)+IFNg(+) at Day 0 Number Analyzed 71 participants 69 participants
74.0
(1.0 to 305.0)
61.0
(1.0 to 181.0)
CD4.CD40L(-)+IL2(+)+TNFa(+)+IFNg(+) at Day 60 Number Analyzed 51 participants 48 participants
210.0
(48.0 to 620.0)
91.5
(29.0 to 329.5)
CD4.CD40L(-)+IL2(+)+TNFa(+)+IFNg(+) at Year 1 Number Analyzed 84 participants 79 participants
956.0
(279.0 to 1540.5)
159.0
(62.0 to 329.5)
CD4.CD40L(-)+IL2(+)+TNFa(+)+IFNg(+) at Year 2 Number Analyzed 76 participants 84 participants
814.5
(483.0 to 1545.5)
215.0
(71.0 to 686.5)
CD4.CD40L(-)+IL2(+)+TNFa(+)+IFNg(+) at Year 3 Number Analyzed 54 participants 60 participants
543.5
(286.0 to 1057.0)
112.0
(38.5 to 257.5)
CD4.CD40L(-)+IL2(+)+TNFa(+)+IFNg(-) at Day 1 Number Analyzed 71 participants 69 participants
20.0
(1.0 to 57.0)
21.0
(1.0 to 57.0)
CD4.CD40L(-)+IL2(+)+TNFa(+)+IFNg(-) at Day 60 Number Analyzed 51 participants 48 participants
89.0
(14.0 to 185.0)
26.0
(1.0 to 67.0)
CD4.CD40L(-)+IL2(+)+TNFa(+)+IFNg(-) at Year 1 Number Analyzed 84 participants 79 participants
152.0
(93.0 to 256.0)
35.0
(2.0 to 98.0)
CD4.CD40L(-)+IL2(+)+TNFa(+)+IFNg(-) at Year 2 Number Analyzed 76 participants 84 participants
190.5
(95.0 to 392.0)
52.5
(8.5 to 107.0)
CD4.CD40L(-)+IL2(+)+TNFa(+)+IFNg(-) at Year 3 Number Analyzed 54 participants 60 participants
86.0
(45.0 to 181.0)
25.5
(1.0 to 88.5)
CD4.CD40L(-)+IL2(+)+TNFa(-)+IFNg(+) at Day 0 Number Analyzed 71 participants 69 participants
52.0
(1.0 to 113.0)
42.0
(9.0 to 126.0)
CD4.CD40L(-)+IL2(+)+TNFa(-)+IFNg(+) at Day 60 Number Analyzed 51 participants 48 participants
180.0
(71.0 to 422.0)
81.0
(28.0 to 177.5)
CD4.CD40L(-)+IL2(+)+TNFa(-)+IFNg(+) at Year 1 Number Analyzed 84 participants 79 participants
41.0
(1.0 to 130.0)
14.0
(1.0 to 39.0)
CD4.CD40L(-)+IL2(+)+TNFa(-)+IFNg(+) at Year 2 Number Analyzed 76 participants 84 participants
136.0
(49.0 to 242.0)
22.5
(1.0 to 89.0)
CD4.CD40L(-)+IL2(+)+TNFa(-)+IFNg(+) at Year 3 Number Analyzed 54 participants 84 participants
31.0
(1.0 to 116.0)
7.5
(1.0 to 22.0)
CD4.CD40L(-)+IL2(+)+TNFa(-)+IFNg(-) at Day 0 Number Analyzed 71 participants 69 participants
86.0
(1.0 to 184.0)
42.0
(1.0 to 188.0)
CD4.CD40L(-)+IL2(+)+TNFa(-)+IFNg(-) at Day 60 Number Analyzed 51 participants 48 participants
242.0
(51.0 to 430.0)
72.0
(1.0 to 186.0)
CD4.CD40L(-)+IL2(+)+TNFa(-)+IFNg(-) at Year 1 Number Analyzed 84 participants 79 participants
87.5
(39.5 to 159.5)
9.0
(1.0 to 47.0)
CD4.CD40L(-)+IL2(+)+TNFa(-)+IFNg(-) at Year 2 Number Analyzed 76 participants 84 participants
136.5
(58.0 to 266.5)
16.5
(1.0 to 78.5)
CD4.CD40L(-)+IL2(+)+TNFa(-)+IFNg(-) at Year 3 Number Analyzed 54 participants 60 participants
51.5
(5.0 to 127.0)
6.0
(1.0 to 48.5)
CD4.CD40L(-)+IL2(-)+TNFa(+)+IFNg(+) at Day 0 Number Analyzed 71 participants 69 participants
42.0
(1.0 to 124.0)
21.0
(1.0 to 77.0)
CD4.CD40L(-)+IL2(-)+TNFa(+)+IFNg(+) at Day 60 Number Analyzed 51 participants 48 participants
186.0
(14.0 to 334.0)
20.5
(1.0 to 118.5)
CD4.CD40L(-)+IL2(-)+TNFa(+)+IFNg(+) at Year 1 Number Analyzed 84 participants 79 participants
121.0
(28.5 to 325.5)
28.0
(1.0 to 101.0)
CD4.CD40L(-)+IL2(-)+TNFa(+)+IFNg(+) at Year 2 Number Analyzed 76 participants 84 participants
118.0
(19.0 to 335.5)
44.0
(1.0 to 186.0)
CD4.CD40L(-)+IL2(-)+TNFa(+)+IFNg(+) at Year 3 Number Analyzed 54 participants 60 participants
94.0
(20.0 to 267.0)
29.0
(1.0 to 97.0)
CD4.CD40L(-)+IL2(-)+TNFa(+)+IFNg(-) at Day 0 Number Analyzed 71 participants 69 participants
1.0
(1.0 to 71.0)
26.0
(1.0 to 99.0)
CD4.CD40L(-)+IL2(-)+TNFa(+)+IFNg(-) at Day 60 Number Analyzed 51 participants 48 participants
72.0
(1.0 to 195.0)
16.5
(1.0 to 66.5)
CD4.CD40L(-)+IL2(-)+TNFa(+)+IFNg(-) at Year 1 Number Analyzed 84 participants 79 participants
92.5
(1.0 to 184.5)
59.0
(1.0 to 196.0)
CD4.CD40L(-)+IL2(-)+TNFa(+)+IFNg(-) at Year 2 Number Analyzed 76 participants 84 participants
5.5
(1.0 to 124.5)
8.5
(1.0 to 152.0)
CD4.CD40L(-)+IL2(-)+TNFa(+)+IFNg(-) at Year 3 Number Analyzed 54 participants 60 participants
32.0
(1.0 to 190.0)
21.0
(1.0 to 156.0)
CD4.CD40L(-)+IL2(-)+TNFa(-)+IFNg(+) at Day 0 Number Analyzed 71 participants 69 participants
71.0
(9.0 to 231.0)
51.0
(1.0 to 128.0)
CD4.CD40L(-)+IL2(-)+TNFa(-)+IFNg(+) at Day 60 Number Analyzed 51 participants 48 participants
708.0
(158.0 to 1621.0)
86.5
(5.0 to 381.0)
CD4.CD40L(-)+IL2(-)+TNFa(-)+IFNg(+) at Year 1 Number Analyzed 84 participants 79 participants
50.0
(7.5 to 110.0)
22.0
(1.0 to 85.0)
CD4.CD40L(-)+IL2(-)+TNFa(-)+IFNg(+) at Year 2 Number Analyzed 76 participants 84 participants
83.0
(2.5 to 206.0)
15.5
(1.0 to 82.0)
CD4.CD40L(-)+IL2(-)+TNFa(-)+IFNg(+) at Year 3 Number Analyzed 54 participants 60 participants
35.5
(1.0 to 152.0)
1.0
(1.0 to 45.0)
13.Secondary Outcome
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
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the "safety and immunogenicity" sub-cohort (i.e. about 150 subjects enrolled in each group and from 2 of the 3 countries [the third country study start was delayed as awaiting regulatory approval]) which included subjects with at least 1 immune result documented.
Arm/Group Title M72AS01 Group Control Group
Hide Arm/Group 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.
Overall Number of Participants Analyzed 68 74
Median (Inter-Quartile Range)
Unit of Measure: T cells per million cells
CD8.CD40L(+)+IL2(+)+TNFa(+)+IFNg(+) at Day 0 Number Analyzed 39 participants 54 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(+)+TNFa(+)+IFNg(+) at Day 60 Number Analyzed 39 participants 38 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(+)+TNFa(+)+IFNg(+) at Year 1 Number Analyzed 68 participants 69 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(+)+TNFa(+)+IFNg(+) at Year 2 Number Analyzed 67 participants 74 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(+)+TNFa(+)+IFNg(+) at Year 3 Number Analyzed 42 participants 53 participants
33.5
(1.0 to 101.0)
1.0
(1.0 to 25.0)
CD8.CD40L(+)+IL2(+)+TNFa(+)+IFNg(-) at Day 0 Number Analyzed 56 participants 54 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(+)+TNFa(+)+IFNg(-) at Day 60 Number Analyzed 39 participants 38 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(+)+TNFa(+)+IFNg(-) at Year 1 Number Analyzed 68 participants 69 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(+)+TNFa(+)+IFNg(-) at Year 2 Number Analyzed 67 participants 74 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(+)+TNFa(+)+IFNg(-) at Year 3 Number Analyzed 42 participants 53 participants
1.0
(1.0 to 34.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(+)+TNFa(-)+IFNg(+) at Day 0 Number Analyzed 56 participants 54 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(+)+TNFa(-)+IFNg(+) at Day 60 Number Analyzed 39 participants 38 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(+)+TNFa(-)+IFNg(+) at Year 1 Number Analyzed 68 participants 69 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(+)+TNFa(-)+IFNg(+) at Year 2 Number Analyzed 67 participants 74 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(+)+TNFa(-)+IFNg(+) at Year 3 Number Analyzed 42 participants 53 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(+)+TNFa(-)+IFNg(-) at Day 0 Number Analyzed 56 participants 54 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(+)+TNFa(-)+IFNg(-) at Day 60 Number Analyzed 39 participants 38 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(+)+TNFa(-)+IFNg(-) at Year 1 Number Analyzed 68 participants 69 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(+)+TNFa(-)+IFNg(-) at Year 2 Number Analyzed 67 participants 74 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(+)+TNFa(-)+IFNg(-) at Year 3 Number Analyzed 42 participants 53 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(-)+TNFa(+)+IFNg(+) at Day 0 Number Analyzed 56 participants 54 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(-)+TNFa(+)+IFNg(+) at Day 60 Number Analyzed 39 participants 38 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(-)+TNFa(+)+IFNg(+) at Year 1 Number Analyzed 68 participants 69 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(-)+TNFa(+)+IFNg(+) at Year 2 Number Analyzed 67 participants 74 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(-)+TNFa(+)+IFNg(+) at Year 3 Number Analyzed 42 participants 53 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(-)+TNFa(+)+IFNg(-) at Day 0 Number Analyzed 56 participants 54 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(-)+TNFa(+)+IFNg(-) at Day 60 Number Analyzed 39 participants 38 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(-)+TNFa(+)+IFNg(-) at Year 1 Number Analyzed 68 participants 69 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(-)+TNFa(+)+IFNg(-) at Year 2 Number Analyzed 67 participants 74 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(-)+TNFa(+)+IFNg(-) at Year 3 Number Analyzed 42 participants 53 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(-)+TNFa(-)+IFNg(+) at Day 0 Number Analyzed 56 participants 54 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(-)+TNFa(-)+IFNg(+) at Day 60 Number Analyzed 39 participants 38 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(-)+TNFa(-)+IFNg(+) at Year 1 Number Analyzed 68 participants 69 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(-)+TNFa(-)+IFNg(+) at Year 2 Number Analyzed 67 participants 74 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(-)+TNFa(-)+IFNg(+) at Year 3 Number Analyzed 42 participants 53 participants
1.0
(1.0 to 20.0)
1.0
(1.0 to 1.0)
CD8.CD40L(+)+IL2(-)+TNFa(-)+IFNg(-) at Day 0 Number Analyzed 56 participants 54 participants
1.0
(1.0 to 187.5)
1.0
(1.0 to 95.0)
CD8.CD40L(+)+IL2(-)+TNFa(-)+IFNg(-) at Day 60 Number Analyzed 39 participants 38 participants
1.0
(1.0 to 112.0)
9.5
(1.0 to 64.0)
CD8.CD40L(+)+IL2(-)+TNFa(-)+IFNg(-) at Year 1 Number Analyzed 68 participants 69 participants
1.0
(1.0 to 65.0)
1.0
(1.0 to 41.0)
CD8.CD40L(+)+IL2(-)+TNFa(-)+IFNg(-) at Year 2 Number Analyzed 67 participants 74 participants
1.0
(1.0 to 96.0)
4.0
(1.0 to 79.0)
CD8.CD40L(+)+IL2(-)+TNFa(-)+IFNg(-) at Year 3 Number Analyzed 42 participants 53 participants
11.5
(1.0 to 110.0)
12.0
(1.0 to 89.0)
CD8.CD40L(-)+IL2(+)+TNFa(+)+IFNg(+) at Day 0 Number Analyzed 56 participants 54 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(-)+IL2(+)+TNFa(+)+IFNg(+) at Day 60 Number Analyzed 39 participants 38 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(-)+IL2(+)+TNFa(+)+IFNg(+) at Year 1 Number Analyzed 68 participants 69 participants
1.0
(1.0 to 43.0)
1.0
(1.0 to 1.0)
CD8.CD40L(-)+IL2(+)+TNFa(+)+IFNg(+) at Year 2 Number Analyzed 67 participants 74 participants
45.0
(1.0 to 96.0)
1.0
(1.0 to 37.0)
CD8.CD40L(-)+IL2(+)+TNFa(+)+IFNg(+) at Year 3 Number Analyzed 42 participants 53 participants
42.0
(1.0 to 75.0)
24.0
(1.0 to 51.0)
CD8.CD40L(-)+IL2(+)+TNFa(+)+IFNg(-) at Day 0 Number Analyzed 56 participants 54 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(-)+IL2(+)+TNFa(+)+IFNg(-) at Day 60 Number Analyzed 39 participants 38 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(-)+IL2(+)+TNFa(+)+IFNg(-) at Year 1 Number Analyzed 68 participants 69 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(-)+IL2(+)+TNFa(+)+IFNg(-) at Year 2 Number Analyzed 67 participants 74 participants
1.0
(1.0 to 27.0)
1.0
(1.0 to 27.0)
CD8.CD40L(-)+IL2(+)+TNFa(+)+IFNg(-) at Year 3 Number Analyzed 42 participants 53 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 14.0)
CD8.CD40L(-)+IL2(+)+TNFa(-)+IFNg(+) at Day 0 Number Analyzed 56 participants 54 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(-)+IL2(+)+TNFa(-)+IFNg(+) at Day 60 Number Analyzed 39 participants 38 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(-)+IL2(+)+TNFa(-)+IFNg(+) at Year 1 Number Analyzed 68 participants 69 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(-)+IL2(+)+TNFa(-)+IFNg(+) at Year 2 Number Analyzed 67 participants 74 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(-)+IL2(+)+TNFa(-)+IFNg(+) at Year 3 Number Analyzed 42 participants 53 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(-)+IL2(+)+TNFa(-)+IFNg(-) at Day 0 Number Analyzed 56 participants 54 participants
1.0
(1.0 to 154.0)
1.0
(1.0 to 235.0)
CD8.CD40L(-)+IL2(+)+TNFa(-)+IFNg(-) at Day 60 Number Analyzed 39 participants 38 participants
69.0
(1.0 to 225.0)
15.5
(1.0 to 155.0)
CD8.CD40L(-)+IL2(+)+TNFa(-)+IFNg(-) at Year 1 Number Analyzed 68 participants 69 participants
1.0
(1.0 to 59.5)
24.0
(1.0 to 73.0)
CD8.CD40L(-)+IL2(+)+TNFa(-)+IFNg(-) at Year 2 Number Analyzed 67 participants 74 participants
7.0
(1.0 to 104.0)
1.0
(1.0 to 64.0)
CD8.CD40L(-)+IL2(+)+TNFa(-)+IFNg(-) at Year 3 Number Analyzed 42 participants 53 participants
1.0
(1.0 to 63.0)
1.0
(1.0 to 72.0)
CD8.CD40L(-)+IL2(-)+TNFa(+)+IFNg(+) at Day 0 Number Analyzed 56 participants 54 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(-)+IL2(-)+TNFa(+)+IFNg(+) at Day 60 Number Analyzed 39 participants 38 participants
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
CD8.CD40L(-)+IL2(-)+TNFa(+)+IFNg(+) at Year 1 Number Analyzed 68 participants 69 participants
1.0
(1.0 to 56.5)
1.0
(1.0 to 81.0)
CD8.CD40L(-)+IL2(-)+TNFa(+)+IFNg(+) at Year 2 Number Analyzed 67 participants 74 participants
1.0
(1.0 to 33.0)
1.0
(1.0 to 44.0)
CD8.CD40L(-)+IL2(-)+TNFa(+)+IFNg(+) at Year 3 Number Analyzed 42 participants 53 participants
1.0
(1.0 to 66.0)
6.0
(1.0 to 131.0)
CD8.CD40L(-)+IL2(-)+TNFa(+)+IFNg(-) at Day 0 Number Analyzed 56 participants 54 participants
1.0
(1.0 to 22.5)
1.0
(1.0 to 65.0)
CD8.CD40L(-)+IL2(-)+TNFa(+)+IFNg(-) at Day 60 Number Analyzed 39 participants 38 participants
19.0
(1.0 to 64.0)
1.0
(1.0 to 2.0)
CD8.CD40L(-)+IL2(-)+TNFa(+)+IFNg(-) at Year 1 Number Analyzed 68 participants 69 participants
1.0
(1.0 to 137.5)
1.0
(1.0 to 79.0)
CD8.CD40L(-)+IL2(-)+TNFa(+)+IFNg(-) at Year 2 Number Analyzed 67 participants 74 participants
1.0
(1.0 to 156.0)
1.0
(1.0 to 125.0)
CD8.CD40L(-)+IL2(-)+TNFa(+)+IFNg(-) at Year 3 Number Analyzed 42 participants 53 participants
1.0
(1.0 to 104.0)
1.0
(1.0 to 313.0)
CD8.CD40L(-)+IL2(-)+TNFa(-)+IFNg(+) at Day 0 Number Analyzed 56 participants 54 participants
26.0
(1.0 to 750)
13.5
(1.0 to 2701)
CD8.CD40L(-)+IL2(-)+TNFa(-)+IFNg(+) at Day 60 Number Analyzed 39 participants 38 participants
18.0
(1.0 to 477)
1.0
(1.0 to 1033)
CD8.CD40L(-)+IL2(-)+TNFa(-)+IFNg(+) at Year 1 Number Analyzed 68 participants 69 participants
1.5
(1.0 to 2981)
1.0
(1.0 to 2819)
CD8.CD40L(-)+IL2(-)+TNFa(-)+IFNg(+) at Year 2 Number Analyzed 67 participants 74 participants
1.0
(1.0 to 978)
3.0
(1.0 to 777)
CD8.CD40L(-)+IL2(-)+TNFa(-)+IFNg(+) at Year 3 Number Analyzed 42 participants 53 participants
1.0
(1.0 to 1384)
16.0
(1.0 to 537)
14.Secondary Outcome
Title M72-specific Antibody Concentrations as Measured by Enzyme Linked Immuno Sorbent Assay (ELISA) in the Safety and Immune Sub-cohort
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the "safety and immunogenicity" sub-cohort (i.e. about 150 subjects enrolled in each group and from 2 of the 3 countries [the third country study start was delayed as awaiting regulatory approval]) which included subjects with at least 1 cell-mediated immune result documented.
Arm/Group Title M72AS01 Group Control Group
Hide Arm/Group 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.
Overall Number of Participants Analyzed 120 124
Geometric Mean (95% Confidence Interval)
Unit of Measure: EU/mL
Anti-M72 at Day 0 Number Analyzed 120 participants 124 participants
1.6
(1.5 to 1.8)
1.6
(1.5 to 1.7)
Anti-M72 at Day 60 Number Analyzed 99 participants 97 participants
547.0
(471.1 to 635.1)
1.6
(1.4 to 1.7)
Anti-M72 at Year 1 Number Analyzed 118 participants 119 participants
41.5
(35.4 to 48.6)
1.7
(1.5 to 1.8)
Anti-M72 at Year 2 Number Analyzed 108 participants 114 participants
30.6
(26.2 to 35.6)
1.6
(1.5 to 1.8)
Anti-M72 at Year 3 Number Analyzed 83 participants 92 participants
27.0
(22.7 to 32.0)
1.6
(1.4 to 1.7)
15.Secondary Outcome
Title Number of Seropositive Subjects for M72 Antibodies Measured by ELISA in the Safety and Immune Sub-cohort
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the "safety and immunogenicity" sub-cohort (i.e. about 150 subjects enrolled in each group and from 2 of the 3 countries [the third country study start was delayed as awaiting regulatory approval]) which included subjects with at least 1 cell-mediated immune result documented.
Arm/Group Title M72AS01 Group Control Group
Hide Arm/Group 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.
Overall Number of Participants Analyzed 120 124
Measure Type: Count of Participants
Unit of Measure: Participants
Anti-M72 at Day 0 Number Analyzed 120 participants 124 participants
11
   9.2%
12
   9.7%
Anti-M72 at Day 60 Number Analyzed 99 participants 97 participants
99
 100.0%
8
   8.2%
Anti-M72 at Year 1 Number Analyzed 118 participants 119 participants
117
  99.2%
14
  11.8%
Anti-M72 at Year 2 Number Analyzed 108 participants 114 participants
108
 100.0%
11
   9.6%
Anti-M72 at Year 3 Number Analyzed 83 participants 92 participants
83
 100.0%
8
   8.7%
Time Frame Solicited local and general symptoms were reported during the 7-day (Days 0-6) post-vaccination period and unsolicited AE(s): during the 30-day (Days 0-29) post-vaccination period. SAE(s): were reported during the entire study period (from Month 0 to Month 36 (Year 3).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title M72AS01 Group Control Group
Hide Arm/Group 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.
All-Cause Mortality
M72AS01 Group Control Group
Affected / at Risk (%) Affected / at Risk (%)
Total   19/1786 (1.06%)      28/1787 (1.57%)    
Hide Serious Adverse Events
M72AS01 Group Control Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   51/1786 (2.86%)      62/1787 (3.47%)    
Blood and lymphatic system disorders     
Hypochromic anaemia  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Iron deficiency anaemia  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Cardiac disorders     
Cardiac disorder  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Cardiac failure congestive  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Ventricular tachycardia  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Endocrine disorders     
Basedow's disease  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Gastrointestinal disorders     
Faecaloma  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Gastric ulcer  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Haematemesis  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Large intestine perforation  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
General disorders     
Accidental death  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Death  1  3/1786 (0.17%)  3 2/1787 (0.11%)  2
Pyrexia  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Sudden death  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Swelling  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Hepatobiliary disorders     
Hepatic cirrhosis  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Immune system disorders     
Hypersensitivity  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Infections and infestations     
Abscess  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Abscess limb  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Acute hiv infection  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Cellulitis  1  1/1786 (0.06%)  1 2/1787 (0.11%)  2
Lymph node tuberculosis  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Malaria  1  2/1786 (0.11%)  2 0/1787 (0.00%)  0
Pelvic inflammatory disease  1  2/1786 (0.11%)  3 0/1787 (0.00%)  0
Pneumonia  1  0/1786 (0.00%)  0 3/1787 (0.17%)  3
Sepsis  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Subcutaneous abscess  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Tuberculosis  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Tuberculosis gastrointestinal  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Typhoid fever  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Injury, poisoning and procedural complications     
Ankle fracture  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Chest injury  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Concussion  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Contusion  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Crush injury  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Femur fracture  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Foot fracture  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Gun shot wound  1  4/1786 (0.22%)  4 11/1787 (0.62%)  11
Head injury  1  3/1786 (0.17%)  3 2/1787 (0.11%)  2
Humerus fracture  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Limb injury  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Lumbar vertebral fracture  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Multiple injuries  1  2/1786 (0.11%)  2 0/1787 (0.00%)  0
Overdose  1  0/1786 (0.00%)  0 3/1787 (0.17%)  3
Pneumothorax traumatic  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Poisoning  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Post-traumatic neck syndrome  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Road traffic accident  1  2/1786 (0.11%)  2 2/1787 (0.11%)  2
Skin laceration  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Soft tissue injury  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Splenic rupture  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Stab wound  1  3/1786 (0.17%)  3 3/1787 (0.17%)  3
Thermal burn  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Traumatic haemothorax  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Wound haematoma  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Metabolism and nutrition disorders     
Diabetic ketoacidosis  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cervix carcinoma  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Squamous cell carcinoma of lung  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Nervous system disorders     
Cerebrovascular accident  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Haemorrhage intracranial  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Hepatic encephalopathy  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Hypertensive encephalopathy  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Seizure  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Pregnancy, puerperium and perinatal conditions     
Abortion incomplete  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Ectopic pregnancy  1  1/1786 (0.06%)  1 1/1787 (0.06%)  1
Foetal distress syndrome  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Pre-eclampsia  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Premature baby  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Premature separation of placenta  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Prolonged labour  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Ruptured ectopic pregnancy  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Psychiatric disorders     
Completed suicide  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Depression  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Schizophrenia  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Substance abuse  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Substance-induced psychotic disorder  1  2/1786 (0.11%)  2 2/1787 (0.11%)  2
Renal and urinary disorders     
Acute kidney injury  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Reproductive system and breast disorders     
Dysfunctional uterine bleeding  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Uterine polyp  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Respiratory, thoracic and mediastinal disorders     
Pneumothorax  1  1/1786 (0.06%)  1 1/1787 (0.06%)  1
Skin and subcutaneous tissue disorders     
Erythema nodosum  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Vascular disorders     
Hypertension  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
1
Term from vocabulary, MedDRA 22.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
M72AS01 Group Control Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1204/1786 (67.41%)      809/1787 (45.27%)    
Blood and lymphatic system disorders     
Anaemia  1  5/1786 (0.28%)  5 3/1787 (0.17%)  3
Eosinophilia  1  3/1786 (0.17%)  3 1/1787 (0.06%)  1
Hypochromic anaemia  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Immune thrombocytopenic purpura  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Iron deficiency anaemia  1  3/1786 (0.17%)  3 0/1787 (0.00%)  0
Lymph node calcification  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Lymph node pain  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Lymphadenitis  1  6/1786 (0.34%)  6 0/1787 (0.00%)  0
Lymphadenopathy  1  13/1786 (0.73%)  15 3/1787 (0.17%)  3
Neutropenia  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Splenomegaly  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Thrombocytopenia  1  3/1786 (0.17%)  3 2/1787 (0.11%)  2
Cardiac disorders     
Bradycardia  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Cardiac failure congestive  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Palpitations  1  1/1786 (0.06%)  1 2/1787 (0.11%)  2
Tachycardia  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Ear and labyrinth disorders     
Cerumen impaction  1  1/1786 (0.06%)  1 1/1787 (0.06%)  1
Ear disorder  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Ear pain  1  4/1786 (0.22%)  4 6/1787 (0.34%)  6
Ear pruritus  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Hypoacusis  1  1/1786 (0.06%)  1 1/1787 (0.06%)  1
Motion sickness  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Tinnitus  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Endocrine disorders     
Goitre  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Eye disorders     
Conjunctival haemorrhage  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Conjunctivitis allergic  1  3/1786 (0.17%)  3 6/1787 (0.34%)  6
Eye discharge  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Eye pain  1  11/1786 (0.62%)  11 5/1787 (0.28%)  6
Eye pruritus  1  2/1786 (0.11%)  2 3/1787 (0.17%)  4
Eye swelling  1  4/1786 (0.22%)  4 2/1787 (0.11%)  2
Eyelid cyst  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Lacrimation increased  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Ocular hyperaemia  1  1/1786 (0.06%)  1 1/1787 (0.06%)  1
Vision blurred  1  4/1786 (0.22%)  4 3/1787 (0.17%)  3
Visual impairment  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Gastrointestinal disorders     
Abdominal discomfort  1  5/1786 (0.28%)  5 6/1787 (0.34%)  7
Abdominal distension  1  0/1786 (0.00%)  0 2/1787 (0.11%)  2
Abdominal pain  1  59/1786 (3.30%)  64 48/1787 (2.69%)  61
Abdominal pain lower  1  3/1786 (0.17%)  3 2/1787 (0.11%)  2
Abdominal pain upper  1  23/1786 (1.29%)  28 28/1787 (1.57%)  30
Anal fissure  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Anal pruritus  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Anal ulcer  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Anorectal discomfort  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Cheilitis  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Colitis  1  1/1786 (0.06%)  1 1/1787 (0.06%)  1
Constipation  1  2/1786 (0.11%)  3 3/1787 (0.17%)  3
Dental caries  1  4/1786 (0.22%)  4 3/1787 (0.17%)  3
Diarrhoea  1  45/1786 (2.52%)  50 30/1787 (1.68%)  37
Diarrhoea haemorrhagic  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Dry mouth  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Dyspepsia  1  3/1786 (0.17%)  3 5/1787 (0.28%)  6
Enteritis  1  2/1786 (0.11%)  2 1/1787 (0.06%)  1
Enterocolitis  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Flatulence  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Food poisoning  1  1/1786 (0.06%)  1 1/1787 (0.06%)  1
Gastric disorder  1  5/1786 (0.28%)  5 1/1787 (0.06%)  1
Gastric ulcer  1  1/1786 (0.06%)  2 0/1787 (0.00%)  0
Gastritis  1  8/1786 (0.45%)  8 9/1787 (0.50%)  11
Gastrointestinal sounds abnormal  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Gastrooesophageal reflux disease  1  2/1786 (0.11%)  2 3/1787 (0.17%)  3
Gingival bleeding  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Gingival pain  1  2/1786 (0.11%)  2 1/1787 (0.06%)  1
Haematochezia  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Haemorrhoids  1  1/1786 (0.06%)  1 3/1787 (0.17%)  4
Lip blister  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Lip swelling  1  1/1786 (0.06%)  1 2/1787 (0.11%)  2
Mouth ulceration  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Nausea  1  47/1786 (2.63%)  52 25/1787 (1.40%)  26
Oesophagitis  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Oral contusion  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Oral pain  1  1/1786 (0.06%)  1 1/1787 (0.06%)  1
Peptic ulcer  1  0/1786 (0.00%)  0 3/1787 (0.17%)  3
Proctalgia  1  2/1786 (0.11%)  2 2/1787 (0.11%)  2
Rectal prolapse  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Stomatitis  1  1/1786 (0.06%)  1 1/1787 (0.06%)  1
Tooth impacted  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Toothache  1  16/1786 (0.90%)  19 22/1787 (1.23%)  25
Vomiting  1  34/1786 (1.90%)  35 16/1787 (0.90%)  16
General disorders     
Administration site pain  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Asthenia  1  19/1786 (1.06%)  22 7/1787 (0.39%)  8
Axillary pain  1  4/1786 (0.22%)  4 0/1787 (0.00%)  0
Chest discomfort  1  1/1786 (0.06%)  1 1/1787 (0.06%)  1
Chest pain  1  30/1786 (1.68%)  31 19/1787 (1.06%)  22
Chills  1  72/1786 (4.03%)  78 8/1787 (0.45%)  9
Facial pain  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Fatigue  1  115/1786 (6.44%)  134 51/1787 (2.85%)  58
Feeling cold  1  12/1786 (0.67%)  12 5/1787 (0.28%)  5
Feeling hot  1  33/1786 (1.85%)  38 17/1787 (0.95%)  20
Feeling of body temperature change  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Hangover  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Hypothermia  1  1/1786 (0.06%)  3 1/1787 (0.06%)  1
Ill-defined disorder  1  1/1786 (0.06%)  1 1/1787 (0.06%)  1
Influenza like illness  1  14/1786 (0.78%)  14 11/1787 (0.62%)  11
Injection site bruising  1  1/1786 (0.06%)  1 1/1787 (0.06%)  1
Injection site discolouration  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Injection site erythema  1  65/1786 (3.64%)  66 1/1787 (0.06%)  1
Injection site hypersensitivity  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Injection site hypoaesthesia  1  3/1786 (0.17%)  3 0/1787 (0.00%)  0
Injection site induration  1  4/1786 (0.22%)  4 0/1787 (0.00%)  0
Injection site joint pain  1  4/1786 (0.22%)  4 0/1787 (0.00%)  0
Injection site lymphadenopathy  1  2/1786 (0.11%)  2 0/1787 (0.00%)  0
Injection site movement impairment  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Injection site pain  1  616/1786 (34.49%)  848 75/1787 (4.20%)  87
Injection site papule  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Injection site pruritus  1  27/1786 (1.51%)  29 5/1787 (0.28%)  6
Injection site rash  1  9/1786 (0.50%)  9 1/1787 (0.06%)  1
Injection site reaction  1  13/1786 (0.73%)  15 1/1787 (0.06%)  1
Injection site swelling  1  192/1786 (10.75%)  221 7/1787 (0.39%)  7
Injection site vesicles  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Injection site warmth  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Injury associated with device  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Malaise  1  35/1786 (1.96%)  35 5/1787 (0.28%)  6
Pain  1  63/1786 (3.53%)  74 10/1787 (0.56%)  11
Peripheral swelling  1  5/1786 (0.28%)  6 2/1787 (0.11%)  2
Pyrexia  1  121/1786 (6.77%)  142 22/1787 (1.23%)  22
Suprapubic pain  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Swelling  1  0/1786 (0.00%)  0 2/1787 (0.11%)  2
Thirst  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Vaccination site pain  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Vessel puncture site pain  1  0/1786 (0.00%)  0 6/1787 (0.34%)  6
Vessel puncture site pruritus  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Hepatobiliary disorders     
Cholecystitis  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Hepatomegaly  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Hyperbilirubinaemia  1  1/1786 (0.06%)  1 1/1787 (0.06%)  1
Immune system disorders     
Food allergy  1  0/1786 (0.00%)  0 2/1787 (0.11%)  2
Hypersensitivity  1  2/1786 (0.11%)  3 1/1787 (0.06%)  1
Seasonal allergy  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Infections and infestations     
Abscess  1  0/1786 (0.00%)  0 3/1787 (0.17%)  3
Abscess jaw  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Abscess limb  1  2/1786 (0.11%)  2 2/1787 (0.11%)  2
Acarodermatitis  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Amoebiasis  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Anal abscess  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Anorectal infection  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Appendicitis  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Ascariasis  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Atypical mycobacterial infection  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Bacterial vaginosis  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Body tinea  1  2/1786 (0.11%)  2 2/1787 (0.11%)  2
Breast abscess  1  0/1786 (0.00%)  0 1/1787 (0.06%)  2
Bronchitis  1  1/1786 (0.06%)  1 3/1787 (0.17%)  3
Candida infection  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Carbuncle  1  1/1786 (0.06%)  1 1/1787 (0.06%)  1
Cellulitis  1  3/1786 (0.17%)  3 2/1787 (0.11%)  2
Cervicitis  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Conjunctivitis  1  5/1786 (0.28%)  5 6/1787 (0.34%)  6
Conjunctivitis bacterial  1  3/1786 (0.17%)  3 0/1787 (0.00%)  0
Cystitis  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Dysentery  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Ear infection  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Folliculitis  1  3/1786 (0.17%)  3 4/1787 (0.22%)  4
Fungal skin infection  1  3/1786 (0.17%)  3 3/1787 (0.17%)  3
Furuncle  1  0/1786 (0.00%)  0 3/1787 (0.17%)  3
Gastroenteritis  1  7/1786 (0.39%)  7 16/1787 (0.90%)  16
Gastroenteritis viral  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Gingival abscess  1  0/1786 (0.00%)  0 2/1787 (0.11%)  2
Gingivitis  1  0/1786 (0.00%)  0 2/1787 (0.11%)  2
Groin abscess  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Helicobacter infection  1  1/1786 (0.06%)  1 2/1787 (0.11%)  2
Helminthic infection  1  2/1786 (0.11%)  2 0/1787 (0.00%)  0
Herpes simplex  1  1/1786 (0.06%)  1 2/1787 (0.11%)  2
Herpes zoster  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Hiv infection  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Impetigo  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Infected bite  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Influenza  1  62/1786 (3.47%)  67 51/1787 (2.85%)  54
Injection site abscess  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Injection site pustule  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Laryngitis  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Lower respiratory tract infection  1  5/1786 (0.28%)  5 8/1787 (0.45%)  8
Malaria  1  52/1786 (2.91%)  53 54/1787 (3.02%)  57
Nasopharyngitis  1  14/1786 (0.78%)  14 15/1787 (0.84%)  15
Oral candidiasis  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Oral herpes  1  1/1786 (0.06%)  1 4/1787 (0.22%)  4
Orchitis  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Otitis media  1  1/1786 (0.06%)  1 4/1787 (0.22%)  4
Paronychia  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Pelvic inflammatory disease  1  1/1786 (0.06%)  1 1/1787 (0.06%)  1
Periodontitis  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Pharyngitis  1  9/1786 (0.50%)  10 10/1787 (0.56%)  10
Pneumonia  1  2/1786 (0.11%)  2 3/1787 (0.17%)  4
Rash pustular  1  2/1786 (0.11%)  2 1/1787 (0.06%)  1
Respiratory tract infection  1  4/1786 (0.22%)  4 7/1787 (0.39%)  7
Rhinitis  1  22/1786 (1.23%)  24 29/1787 (1.62%)  29
Salmonellosis  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Sepsis  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Sexually transmitted disease  1  2/1786 (0.11%)  2 0/1787 (0.00%)  0
Sinusitis  1  6/1786 (0.34%)  6 8/1787 (0.45%)  9
Skin bacterial infection  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Skin infection  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Subcutaneous abscess  1  4/1786 (0.22%)  4 1/1787 (0.06%)  2
Tinea capitis  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Tinea infection  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Tinea pedis  1  1/1786 (0.06%)  1 2/1787 (0.11%)  2
Tinea versicolour  1  5/1786 (0.28%)  5 4/1787 (0.22%)  4
Tonsillitis  1  4/1786 (0.22%)  4 7/1787 (0.39%)  7
Tooth abscess  1  2/1786 (0.11%)  2 3/1787 (0.17%)  3
Typhoid fever  1  3/1786 (0.17%)  3 2/1787 (0.11%)  2
Upper respiratory tract infection  1  64/1786 (3.58%)  70 72/1787 (4.03%)  76
Urethritis  1  1/1786 (0.06%)  1 2/1787 (0.11%)  2
Urinary tract infection  1  9/1786 (0.50%)  10 15/1787 (0.84%)  16
Vaginal infection  1  0/1786 (0.00%)  0 3/1787 (0.17%)  3
Varicella  1  0/1786 (0.00%)  0 3/1787 (0.17%)  3
Viral rash  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Vulval abscess  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Vulvovaginal candidiasis  1  3/1786 (0.17%)  3 1/1787 (0.06%)  1
Vulvovaginal mycotic infection  1  1/1786 (0.06%)  1 2/1787 (0.11%)  3
Wound infection  1  2/1786 (0.11%)  2 0/1787 (0.00%)  0
Injury, poisoning and procedural complications     
Alcohol poisoning  1  0/1786 (0.00%)  0 2/1787 (0.11%)  2
Animal bite  1  2/1786 (0.11%)  2 2/1787 (0.11%)  2
Arthropod bite  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Arthropod sting  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Contusion  1  2/1786 (0.11%)  2 1/1787 (0.06%)  1
Eye contusion  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Face injury  1  1/1786 (0.06%)  1 1/1787 (0.06%)  1
Gun shot wound  1  1/1786 (0.06%)  1 1/1787 (0.06%)  1
Hand fracture  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Head injury  1  2/1786 (0.11%)  2 2/1787 (0.11%)  2
Heat stroke  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Injection related reaction  1  1/1786 (0.06%)  2 1/1787 (0.06%)  2
Ligament sprain  1  3/1786 (0.17%)  4 3/1787 (0.17%)  3
Limb injury  1  3/1786 (0.17%)  3 5/1787 (0.28%)  5
Lip injury  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Mouth injury  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Muscle strain  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Penis injury  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Procedural pain  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Radius fracture  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Road traffic accident  1  0/1786 (0.00%)  0 2/1787 (0.11%)  2
Scar  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Skin abrasion  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Skin injury  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Skin laceration  1  4/1786 (0.22%)  4 8/1787 (0.45%)  8
Soft tissue injury  1  6/1786 (0.34%)  6 3/1787 (0.17%)  3
Stab wound  1  3/1786 (0.17%)  3 2/1787 (0.11%)  2
Tendon injury  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Thermal burn  1  1/1786 (0.06%)  1 2/1787 (0.11%)  2
Upper limb fracture  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Vaccination complication  1  2/1786 (0.11%)  6 3/1787 (0.17%)  3
Wound  1  2/1786 (0.11%)  2 4/1787 (0.22%)  4
Investigations     
Alanine aminotransferase increased  1  4/1786 (0.22%)  4 6/1787 (0.34%)  6
Aspartate aminotransferase increased  1  4/1786 (0.22%)  4 5/1787 (0.28%)  5
Blood pressure diastolic increased  1  1/1786 (0.06%)  1 1/1787 (0.06%)  1
Blood pressure increased  1  5/1786 (0.28%)  5 4/1787 (0.22%)  4
Blood pressure systolic increased  1  3/1786 (0.17%)  3 3/1787 (0.17%)  3
Body temperature decreased  1  0/1786 (0.00%)  0 1/1787 (0.06%)  3
Body temperature increased  1  2/1786 (0.11%)  2 0/1787 (0.00%)  0
Haematocrit decreased  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Haemoglobin decreased  1  6/1786 (0.34%)  6 3/1787 (0.17%)  3
Heart rate increased  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Hiv test positive  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Lymphocyte count decreased  1  1/1786 (0.06%)  1 1/1787 (0.06%)  1
Neutrophil count decreased  1  9/1786 (0.50%)  9 6/1787 (0.34%)  6
Neutrophil count increased  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Platelet count decreased  1  1/1786 (0.06%)  2 0/1787 (0.00%)  0
Respiratory rate increased  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Weight decreased  1  12/1786 (0.67%)  12 8/1787 (0.45%)  8
White blood cell count decreased  1  1/1786 (0.06%)  1 1/1787 (0.06%)  1
White blood cell count increased  1  2/1786 (0.11%)  2 2/1787 (0.11%)  2
Metabolism and nutrition disorders     
Decreased appetite  1  33/1786 (1.85%)  34 11/1787 (0.62%)  11
Dehydration  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Gout  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Hypoalbuminanemia  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Hyponatraemia  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Increased appetite  1  0/1786 (0.00%)  0 2/1787 (0.11%)  2
Musculoskeletal and connective tissue disorders     
Arthralgia  1  31/1786 (1.74%)  31 21/1787 (1.18%)  22
Arthritis  1  0/1786 (0.00%)  0 2/1787 (0.11%)  2
Arthropathy  1  3/1786 (0.17%)  3 1/1787 (0.06%)  1
Back pain  1  66/1786 (3.70%)  76 32/1787 (1.79%)  35
Bone pain  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Bone swelling  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Flank pain  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Joint stiffness  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Joint swelling  1  4/1786 (0.22%)  4 0/1787 (0.00%)  0
Limb discomfort  1  2/1786 (0.11%)  2 2/1787 (0.11%)  3
Mobility decreased  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Muscle spasms  1  2/1786 (0.11%)  2 8/1787 (0.45%)  8
Muscle twitching  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Muscular weakness  1  4/1786 (0.22%)  4 2/1787 (0.11%)  2
Musculoskeletal chest pain  1  4/1786 (0.22%)  4 5/1787 (0.28%)  5
Musculoskeletal pain  1  10/1786 (0.56%)  11 10/1787 (0.56%)  11
Musculoskeletal stiffness  1  3/1786 (0.17%)  4 1/1787 (0.06%)  1
Myalgia  1  84/1786 (4.70%)  88 25/1787 (1.40%)  28
Myositis  1  3/1786 (0.17%)  3 1/1787 (0.06%)  1
Neck pain  1  15/1786 (0.84%)  17 6/1787 (0.34%)  7
Osteoarthritis  1  2/1786 (0.11%)  2 0/1787 (0.00%)  0
Pain in extremity  1  26/1786 (1.46%)  30 18/1787 (1.01%)  18
Pain in jaw  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Rotator cuff syndrome  1  1/1786 (0.06%)  1 1/1787 (0.06%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Anogenital warts  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Fibroadenoma of breast  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Skin papilloma  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Nervous system disorders     
Ageusia  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Dizziness  1  120/1786 (6.72%)  132 93/1787 (5.20%)  104
Headache  1  620/1786 (34.71%)  879 341/1787 (19.08%)  483
Hypoaesthesia  1  7/1786 (0.39%)  7 4/1787 (0.22%)  4
Lethargy  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Neuralgia  1  1/1786 (0.06%)  1 2/1787 (0.11%)  2
Neuritis  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Neuropathy peripheral  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Optic neuritis  1  0/1786 (0.00%)  0 2/1787 (0.11%)  2
Paraesthesia  1  3/1786 (0.17%)  3 1/1787 (0.06%)  1
Poor quality sleep  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Post-traumatic headache  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Presyncope  1  2/1786 (0.11%)  2 0/1787 (0.00%)  0
Seizure  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Somnolence  1  5/1786 (0.28%)  5 3/1787 (0.17%)  3
Syncope  1  1/1786 (0.06%)  1 1/1787 (0.06%)  1
Tension headache  1  2/1786 (0.11%)  2 6/1787 (0.34%)  6
Transient ischaemic attack  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Psychiatric disorders     
Anxiety  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Insomnia  1  3/1786 (0.17%)  3 4/1787 (0.22%)  4
Libido increased  1  2/1786 (0.11%)  2 0/1787 (0.00%)  0
Renal and urinary disorders     
Dysuria  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Hypertonic bladder  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Micturition disorder  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Pollakiuria  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Urethral discharge  1  1/1786 (0.06%)  1 1/1787 (0.06%)  1
Reproductive system and breast disorders     
Breast mass  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Breast pain  1  1/1786 (0.06%)  1 2/1787 (0.11%)  2
Dysfunctional uterine bleeding  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Dysmenorrhoea  1  6/1786 (0.34%)  6 7/1787 (0.39%)  7
Erectile dysfunction  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Genital ulceration  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Menorrhagia  1  4/1786 (0.22%)  4 6/1787 (0.34%)  6
Menstruation irregular  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Metrorrhagia  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Pelvic pain  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Penile discharge  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Pruritus genital  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Scrotal pain  1  1/1786 (0.06%)  1 0/1787 (0.00%)  0
Vaginal discharge  1  1/1786 (0.06%)  1 3/1787 (0.17%)  3
Vaginal haemorrhage  1  0/1786 (0.00%)  0 1/1787 (0.06%)  1
Respiratory, thoracic and mediastinal disorders     
Asthma  1  2/1786 (0.11%)  2 2/1787 (0.11%)  2
Bronchial hyperreactivity  1