Human Immunodeficiency Virus
Conditions
Keywords
Mycobacterium tuberculosis, M72/AS01E Vaccine, Antiretroviral therapy, Mtb, HIV, TB vaccine
Brief summary
The purpose of this study is to assess the safety and immunogenicity of M72/AS01E vaccination in virally suppressed, antiretroviral-treated participants with human immunodeficiency virus infection (HIV).
Interventions
BIOLOGICALM72/AS01E Mycobacterium tuberculosis vaccine
Participants will receive an intramuscular dose of M72 (10 micrograms of recombinant fusion protein) reconstituted with AS01E (an adjuvant system), on Day 1 and Day 29
BIOLOGICALPlacebo
Participants will receive an intramuscular dose of saline (0.9% NaCl), on Day 1 and Day 29
Sponsors
Wellcome Trust
Gates Medical Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
* Participant with documented human immunodeficiency virus (HIV) infection who fulfill all of the following: * Has reactive anti-HIV antibody at screening * On antiretroviral therapy (ART) for at least 3 consecutive months at screening * Has documented HIV RNA \<200 copies/mL at screening * Participants with CD4+ cell counts ≥200 cells/μL at screening * Participants have had tuberculosis (TB) preventive therapy (TPT) in the past and are not receiving TPT at the time of screening, according to the judgment of the investigators * Participants who are healthy as determined by medical evaluation including medical history, physical examination and laboratory tests * Capable of giving signed informed consent and informed assent (if appropriate), which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) or informed assent form, and in the protocol. * Female participants of childbearing potential must agree not to become pregnant from the time of study enrollment for one year after study intervention. Women physically capable of pregnancy, sexually active and having no history of hysterectomy or tubal ligation or menopause must agree to use an effective method of avoiding pregnancy during this period. * Participants who agree to stay in contact with the study site for the duration of the study, provide updated contact information as necessary, and have no current plans to relocate from the study area for the duration of the study.
Exclusion criteria
* Acute illness or fever ≥99.5°F (or ≥37.5˚C) on Day 1 * History of active TB disease * Evidence of active TB disease with any of the following: * Have symptoms or signs of TB disease * Have a positive sputum Xpert MTB/RIF assay (only in participants with sputum sample at screening) * Are on treatment for active TB disease * Evidence and/or history of clinically significant medical conditions (other than HIV infection) as judged by the investigator, including malignancies * Any current medical, psychiatric, occupational, or substance abuse problems that, in the opinion of the investigator, will make it unlikely that the participant will comply with the protocol * Any medications or other therapies that may impact the immune system such as immune globulin, interferon, immunomodulators, cytotoxic drugs or other drugs known to be frequently associated with major organ toxicity as determined by the investigator, within 90 days prior to Day 1 * Immunosuppressive agents including systemic steroids - prior corticosteroid therapy within 90 days prior to Day 1 (permitted: 5 mg/day prednisone equivalent, inhaled, topical, and intra-articular corticosteroids) * Receipt or donation of blood or blood products within 90 days prior to Day 1 or planned receipt or donation during the study period * Participation in an interventional clinical trial and/or receipt of any investigational drug within 180 days prior to signing informed consent or assent * Receipt of any vaccine in the period starting 7 days before, and ending 7 days after, each dose of the study vaccine * History of previous administration of experimental Mycobacterium tuberculosis vaccine * Safety laboratory values outside of normal range, for age and sex that are suggestive of a disease state (Grade 1 abnormalities, as per Division of AIDS \[DAIDS\] toxicity table version 2.1, will not lead to exclusion if the investigator considers them not clinically significant.) * Urinalysis abnormality greater than Grade 1 on the Toxicity Scale (with the exception of hematuria in a menstruating female), or urinalysis abnormality judged clinically significant by the investigator * Current hepatitis B and/or hepatitis C infection * Indeterminate QFT result * History of allergy or hypersensitivity to the study drug, excipients or related substances * Shared residence with an individual who is receiving TB treatment or with someone who is known to have incompletely treated TB, e.g., Xpert MTB/RIF assay-positive, polymerase chain reaction (PCR)-positive, culture-positive, smear-positive TB, or clinically diagnosed unconfirmed TB * Female participants with any one of the following conditions: currently pregnant or lactating/nursing; having positive serum pregnancy test during the screening window, planning a pregnancy within 1 year after first dose of study product * Individuals who are acting as study personnel or immediate family members (brother, sister, child, parent) or the spouse/partner of study personnel. * Child in Care
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Solicited Adverse Events (AEs) Through 7 Days Post Dose 1 of Study Intervention | Day 1 through Day 7 (after first vaccination) | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE does not necessarily have a causal relationship with the intervention. Solicited AEs were defined events that participants were specifically asked about and which were noted by participants in the diary card. Solicited local AEs included pain, redness and swelling and general body symptoms such as fever, headache, fatigue, gastrointestinal symptoms, and myalgia. |
| Number of Participants With Solicited AEs Through 7 Days Post Dose 2 of Study Intervention | Day 29 through Day 35 (after second vaccination) | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE does not necessarily have a causal relationship with the intervention. Solicited AEs were defined events that participants were specifically asked about and which were noted by participants in the diary card. Solicited local AEs included pain, redness and swelling and general body symptoms such as fever, headache, fatigue, gastrointestinal symptoms, and myalgia. |
| Number of Participants With Unsolicited AEs Through 28 Days Post Dose 1 of Study Intervention | Day 1 through Day 28 | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE does not necessarily have a causal relationship with the intervention. Unsolicited AEs were all AEs for which the participant was not specifically questioned in the participant diary card. Number of Participants With Unsolicited AEs Through 28 Days after first vaccination has been presented. |
| Number of Participants With Unsolicited AEs Through 28 Days Post Dose 2 of Study Intervention | Day 29 through Day 57 | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE does not necessarily have a causal relationship with the intervention. Unsolicited AEs were all AEs for which the participant was not specifically questioned in the participant diary card. Number of Participants With Unsolicited AEs Through 28 Days after second vaccination has been presented. |
| Number of Participants Reporting Serious AEs (SAEs) | Up to Day 390 | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Number of Participants reporting SAEs has been presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Potential Immune-mediated Diseases (pIMDs) | Up to Day 390 | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. pIMDs are a subset of AEs that included autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology. Number of Participants With Potential Immune-mediated Diseases (pIMDs) has been presented |
| Percentage of M72-specific CD4+ T Cells and CD8+ T Cells Exhibiting Cytokine Response With Background Subtracted | At Baseline, Day 57, and Day 390 | Blood samples were analyzed for M72-specific CD4+ and CD8+ T-cells exhibiting cytokine response (IFN-gamma and/or IL-2) with background subtracted. Baseline is defined as the last non-missing assessment (scheduled or unscheduled) prior to the first study vaccination. |
| Number of Participants With Clinically Significant Hematology Assessments of Grade 3 or Above After Baseline | Up to Day 390 | Blood samples were collected for the assessment of hemoglobin, leukocytes and platelets. Baseline was defined as last non-missing assessment prior to first vaccination. Laboratory grades were evaluated using the Common Terminology Criteria for AEs (CTCAE version (v)5.0) with grading as: Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening or disabling. Number of Participants With Clinically Significant hematology assessments of Grade 3 and Grade 4 has been presented. |
| Number of Participants With Clinically Significant Chemistry Assessments of Grade 3 or Above After Baseline | Up to Day 390 | Blood samples were collected for the assessment of Alanine Aminotransferase, Aspartate Aminotransferase and total bilirubin. Baseline was defined as last non-missing assessment prior to first vaccination. Laboratory grades were evaluated using the CTCAE v5.0 with grading as: Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening or disabling. Number of Participants With Clinically Significant chemistry assessments of Grade 3 and Grade 4 has been presented. |
| M72-specific Antibody Titers | Day 1, Day 29, Day 57, Day 210 and Day 390 | Blood samples for immunogenicity evaluation of M72-specific IgG antibody in serum were collected. On Day 1 and Day 29 visits, samples were collected prior to study intervention administration. Humoral M72-specific IgG antibodies were measured by enzyme-linked immunosorbent assay (ELISA). |
| Number of M72 Specific CD4+ and CD8+ T Cell Responders Based on Cytokine Response | Day 57 and Day 390 | Blood samples were analyzed for M72-specific CD4+ and CD8+ T-cell responses based on IFN-gamma and/or IL-2 expression. The CD4+ and CD8+ categories for each timepoint are mutually exclusive. |
Countries
South Africa
Participant flow
Recruitment details
The study was conducted in South Africa.
Pre-assignment details
This was a randomized, placebo-controlled, observer-blind, phase 2 study to evaluate safety and immunogenicity of the investigational M72/AS01E Mycobacterium tuberculosis (Mtb) vaccine in virally suppressed, antiretroviral-treated participants with human immunodeficiency virus (HIV).
Participants by arm
| Arm | Count |
|---|---|
| M72/AS01E Participants were randomized to receive an intramuscular dose of M72/AS01E: M72 (10 micrograms of recombinant fusion protein) reconstituted with AS01E (an adjuvant system), on Day 1 and Day 29 | 201 |
| Placebo Participants were randomized to receive an intramuscular dose of placebo (saline \[0.9% sodium chloride {NaCl}\]), on Day 1 and Day 29 | 200 |
| Total | 401 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 11 |
| Overall Study | Moved from the study area | 1 | 4 |
| Overall Study | Other | 2 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Total | M72/AS01E | Placebo |
|---|---|---|---|
| Age, Continuous | 29.5 Years STANDARD_DEVIATION 4.32 | 29.4 Years STANDARD_DEVIATION 4.17 | 29.6 Years STANDARD_DEVIATION 4.47 |
| Cluster of differentiation 4 (CD4+) <200*10^6 cells/L | 0 10^6 cells/liter (L) | 0 10^6 cells/liter (L) | 0 10^6 cells/liter (L) |
| Cluster of differentiation 4 (CD4+) 200-349*10^6 cells/L | 12 10^6 cells/liter (L) | 7 10^6 cells/liter (L) | 5 10^6 cells/liter (L) |
| Cluster of differentiation 4 (CD4+) 350-499*10^6 cells/L | 44 10^6 cells/liter (L) | 20 10^6 cells/liter (L) | 24 10^6 cells/liter (L) |
| Cluster of differentiation 4 (CD4+) >=500*10^6 cells/L | 345 10^6 cells/liter (L) | 174 10^6 cells/liter (L) | 171 10^6 cells/liter (L) |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 401 Participants | 201 Participants | 200 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Human immunodeficiency virus (HIV) ribonucleic acid (RNA) viral load <=200 copies per mL | 71 copies per mL | 36 copies per mL | 35 copies per mL |
| Human immunodeficiency virus (HIV) ribonucleic acid (RNA) viral load >200 copies per mL | 6 copies per mL | 3 copies per mL | 3 copies per mL |
| Human immunodeficiency virus (HIV) ribonucleic acid (RNA) viral load Not Detected | 324 copies per mL | 162 copies per mL | 162 copies per mL |
| QuantiFERON®-TB Gold Plus assay status Negative | 208 Participants | 108 Participants | 100 Participants |
| QuantiFERON®-TB Gold Plus assay status Positive | 193 Participants | 93 Participants | 100 Participants |
| Race/Ethnicity, Customized Black | 392 Participants | 196 Participants | 196 Participants |
| Race/Ethnicity, Customized Southern African Coloured | 9 Participants | 5 Participants | 4 Participants |
| Sex: Female, Male Female | 351 Participants | 175 Participants | 176 Participants |
| Sex: Female, Male Male | 50 Participants | 26 Participants | 24 Participants |
| Weight | 73.8 Kilograms STANDARD_DEVIATION 19.36 | 73.4 Kilograms STANDARD_DEVIATION 19.93 | 74.3 Kilograms STANDARD_DEVIATION 18.81 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 201 | 1 / 200 |
| other Total, other adverse events | 191 / 201 | 158 / 200 |
| serious Total, serious adverse events | 4 / 201 | 5 / 200 |
Outcome results
Primary
Number of Participants Reporting Serious AEs (SAEs)
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Number of Participants reporting SAEs has been presented.
Time frame: Up to Day 390
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| M72/AS01E | Number of Participants Reporting Serious AEs (SAEs) | 4 Participants |
| Placebo | Number of Participants Reporting Serious AEs (SAEs) | 5 Participants |
Primary
Number of Participants With Solicited Adverse Events (AEs) Through 7 Days Post Dose 1 of Study Intervention
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE does not necessarily have a causal relationship with the intervention. Solicited AEs were defined events that participants were specifically asked about and which were noted by participants in the diary card. Solicited local AEs included pain, redness and swelling and general body symptoms such as fever, headache, fatigue, gastrointestinal symptoms, and myalgia.
Time frame: Day 1 through Day 7 (after first vaccination)
Population: Safety Population: included all participants randomly assigned to study intervention and who received at least one dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| M72/AS01E | Number of Participants With Solicited Adverse Events (AEs) Through 7 Days Post Dose 1 of Study Intervention | Any injection site symptom | 155 Participants |
| M72/AS01E | Number of Participants With Solicited Adverse Events (AEs) Through 7 Days Post Dose 1 of Study Intervention | Any general body symptom | 132 Participants |
| Placebo | Number of Participants With Solicited Adverse Events (AEs) Through 7 Days Post Dose 1 of Study Intervention | Any injection site symptom | 49 Participants |
| Placebo | Number of Participants With Solicited Adverse Events (AEs) Through 7 Days Post Dose 1 of Study Intervention | Any general body symptom | 109 Participants |
Primary
Number of Participants With Solicited AEs Through 7 Days Post Dose 2 of Study Intervention
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE does not necessarily have a causal relationship with the intervention. Solicited AEs were defined events that participants were specifically asked about and which were noted by participants in the diary card. Solicited local AEs included pain, redness and swelling and general body symptoms such as fever, headache, fatigue, gastrointestinal symptoms, and myalgia.
Time frame: Day 29 through Day 35 (after second vaccination)
Population: Safety Population: included all participants randomly assigned to study intervention and who received at least one dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| M72/AS01E | Number of Participants With Solicited AEs Through 7 Days Post Dose 2 of Study Intervention | Any injection site symptom | 147 Participants |
| M72/AS01E | Number of Participants With Solicited AEs Through 7 Days Post Dose 2 of Study Intervention | Any general body symptom | 134 Participants |
| Placebo | Number of Participants With Solicited AEs Through 7 Days Post Dose 2 of Study Intervention | Any general body symptom | 83 Participants |
| Placebo | Number of Participants With Solicited AEs Through 7 Days Post Dose 2 of Study Intervention | Any injection site symptom | 29 Participants |
Primary
Number of Participants With Unsolicited AEs Through 28 Days Post Dose 1 of Study Intervention
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE does not necessarily have a causal relationship with the intervention. Unsolicited AEs were all AEs for which the participant was not specifically questioned in the participant diary card. Number of Participants With Unsolicited AEs Through 28 Days after first vaccination has been presented.
Time frame: Day 1 through Day 28
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| M72/AS01E | Number of Participants With Unsolicited AEs Through 28 Days Post Dose 1 of Study Intervention | 67 Participants |
| Placebo | Number of Participants With Unsolicited AEs Through 28 Days Post Dose 1 of Study Intervention | 67 Participants |
Primary
Number of Participants With Unsolicited AEs Through 28 Days Post Dose 2 of Study Intervention
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE does not necessarily have a causal relationship with the intervention. Unsolicited AEs were all AEs for which the participant was not specifically questioned in the participant diary card. Number of Participants With Unsolicited AEs Through 28 Days after second vaccination has been presented.
Time frame: Day 29 through Day 57
Population: Safety Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| M72/AS01E | Number of Participants With Unsolicited AEs Through 28 Days Post Dose 2 of Study Intervention | 53 Participants |
| Placebo | Number of Participants With Unsolicited AEs Through 28 Days Post Dose 2 of Study Intervention | 41 Participants |
Secondary
M72-specific Antibody Titers
Blood samples for immunogenicity evaluation of M72-specific IgG antibody in serum were collected. On Day 1 and Day 29 visits, samples were collected prior to study intervention administration. Humoral M72-specific IgG antibodies were measured by enzyme-linked immunosorbent assay (ELISA).
Time frame: Day 1, Day 29, Day 57, Day 210 and Day 390
Population: Per-Protocol (PP) Population: included all participants randomly assigned to study intervention, who received the study interventions as planned and did not substantially deviate from the protocol procedures. Only those participants with data available at the specified data points were analyzed
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| M72/AS01E | M72-specific Antibody Titers | Day 29 | 13.28 Equivalent units per mL (EU/mL) |
| M72/AS01E | M72-specific Antibody Titers | Day 210 | 52.23 Equivalent units per mL (EU/mL) |
| M72/AS01E | M72-specific Antibody Titers | Day 57 | 479.70 Equivalent units per mL (EU/mL) |
| M72/AS01E | M72-specific Antibody Titers | Day 390 | 32.43 Equivalent units per mL (EU/mL) |
| M72/AS01E | M72-specific Antibody Titers | Day 1 | 2.72 Equivalent units per mL (EU/mL) |
| Placebo | M72-specific Antibody Titers | Day 390 | 2.77 Equivalent units per mL (EU/mL) |
| Placebo | M72-specific Antibody Titers | Day 1 | 2.77 Equivalent units per mL (EU/mL) |
| Placebo | M72-specific Antibody Titers | Day 29 | 2.77 Equivalent units per mL (EU/mL) |
| Placebo | M72-specific Antibody Titers | Day 57 | 2.77 Equivalent units per mL (EU/mL) |
| Placebo | M72-specific Antibody Titers | Day 210 | 2.77 Equivalent units per mL (EU/mL) |
Secondary
Number of M72 Specific CD4+ and CD8+ T Cell Responders Based on Cytokine Response
Blood samples were analyzed for M72-specific CD4+ and CD8+ T-cell responses based on IFN-gamma and/or IL-2 expression. The CD4+ and CD8+ categories for each timepoint are mutually exclusive.
Time frame: Day 57 and Day 390
Population: Per-Protocol for Cellular Immunogenicity Population comprises all participants in PP population randomly selected to have immunogenicity assays performed. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| M72/AS01E | Number of M72 Specific CD4+ and CD8+ T Cell Responders Based on Cytokine Response | CD4+ Responders on Day 57 | 92 Participants |
| M72/AS01E | Number of M72 Specific CD4+ and CD8+ T Cell Responders Based on Cytokine Response | CD4+ non-responders on Day 57 | 4 Participants |
| M72/AS01E | Number of M72 Specific CD4+ and CD8+ T Cell Responders Based on Cytokine Response | CD4+ Responders on Day 390 | 85 Participants |
| M72/AS01E | Number of M72 Specific CD4+ and CD8+ T Cell Responders Based on Cytokine Response | CD4+ non-responders on Day 390 | 11 Participants |
| M72/AS01E | Number of M72 Specific CD4+ and CD8+ T Cell Responders Based on Cytokine Response | CD8+ Responders on Day 57 | 14 Participants |
| M72/AS01E | Number of M72 Specific CD4+ and CD8+ T Cell Responders Based on Cytokine Response | CD8+ non-responders on Day 57 | 82 Participants |
| M72/AS01E | Number of M72 Specific CD4+ and CD8+ T Cell Responders Based on Cytokine Response | CD8+ Responders on Day 390 | 10 Participants |
| M72/AS01E | Number of M72 Specific CD4+ and CD8+ T Cell Responders Based on Cytokine Response | CD8+ non-Responders on Day 390 | 86 Participants |
| Placebo | Number of M72 Specific CD4+ and CD8+ T Cell Responders Based on Cytokine Response | CD8+ non-Responders on Day 390 | 29 Participants |
| Placebo | Number of M72 Specific CD4+ and CD8+ T Cell Responders Based on Cytokine Response | CD4+ Responders on Day 57 | 6 Participants |
| Placebo | Number of M72 Specific CD4+ and CD8+ T Cell Responders Based on Cytokine Response | CD8+ Responders on Day 57 | 3 Participants |
| Placebo | Number of M72 Specific CD4+ and CD8+ T Cell Responders Based on Cytokine Response | CD4+ non-responders on Day 57 | 25 Participants |
| Placebo | Number of M72 Specific CD4+ and CD8+ T Cell Responders Based on Cytokine Response | CD8+ Responders on Day 390 | 3 Participants |
| Placebo | Number of M72 Specific CD4+ and CD8+ T Cell Responders Based on Cytokine Response | CD4+ Responders on Day 390 | 8 Participants |
| Placebo | Number of M72 Specific CD4+ and CD8+ T Cell Responders Based on Cytokine Response | CD8+ non-responders on Day 57 | 28 Participants |
| Placebo | Number of M72 Specific CD4+ and CD8+ T Cell Responders Based on Cytokine Response | CD4+ non-responders on Day 390 | 24 Participants |
Secondary
Number of Participants With Clinically Significant Chemistry Assessments of Grade 3 or Above After Baseline
Blood samples were collected for the assessment of Alanine Aminotransferase, Aspartate Aminotransferase and total bilirubin. Baseline was defined as last non-missing assessment prior to first vaccination. Laboratory grades were evaluated using the CTCAE v5.0 with grading as: Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening or disabling. Number of Participants With Clinically Significant chemistry assessments of Grade 3 and Grade 4 has been presented.
Time frame: Up to Day 390
Population: Safety Population. Only those participants with data available at the specified data points were analyzed
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| M72/AS01E | Number of Participants With Clinically Significant Chemistry Assessments of Grade 3 or Above After Baseline | Alanine Aminotransferase: Grade 3 | 0 Participants |
| M72/AS01E | Number of Participants With Clinically Significant Chemistry Assessments of Grade 3 or Above After Baseline | Alanine Aminotransferase: Grade 4 | 0 Participants |
| M72/AS01E | Number of Participants With Clinically Significant Chemistry Assessments of Grade 3 or Above After Baseline | Aspartate Aminotransferase: Grade 3 | 0 Participants |
| M72/AS01E | Number of Participants With Clinically Significant Chemistry Assessments of Grade 3 or Above After Baseline | Aspartate Aminotransferase: Grade 4 | 0 Participants |
| M72/AS01E | Number of Participants With Clinically Significant Chemistry Assessments of Grade 3 or Above After Baseline | Total bilirubin: Grade 3 | 0 Participants |
| M72/AS01E | Number of Participants With Clinically Significant Chemistry Assessments of Grade 3 or Above After Baseline | Total bilirubin: Grade 4 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Chemistry Assessments of Grade 3 or Above After Baseline | Total bilirubin: Grade 3 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Chemistry Assessments of Grade 3 or Above After Baseline | Alanine Aminotransferase: Grade 3 | 1 Participants |
| Placebo | Number of Participants With Clinically Significant Chemistry Assessments of Grade 3 or Above After Baseline | Aspartate Aminotransferase: Grade 4 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Chemistry Assessments of Grade 3 or Above After Baseline | Alanine Aminotransferase: Grade 4 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Chemistry Assessments of Grade 3 or Above After Baseline | Total bilirubin: Grade 4 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Chemistry Assessments of Grade 3 or Above After Baseline | Aspartate Aminotransferase: Grade 3 | 1 Participants |
Secondary
Number of Participants With Clinically Significant Hematology Assessments of Grade 3 or Above After Baseline
Blood samples were collected for the assessment of hemoglobin, leukocytes and platelets. Baseline was defined as last non-missing assessment prior to first vaccination. Laboratory grades were evaluated using the Common Terminology Criteria for AEs (CTCAE version (v)5.0) with grading as: Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening or disabling. Number of Participants With Clinically Significant hematology assessments of Grade 3 and Grade 4 has been presented.
Time frame: Up to Day 390
Population: Safety Population. Only those participants with data available at the specified data points were analyzed
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| M72/AS01E | Number of Participants With Clinically Significant Hematology Assessments of Grade 3 or Above After Baseline | Leukocytes: Grade 4 | 0 Participants |
| M72/AS01E | Number of Participants With Clinically Significant Hematology Assessments of Grade 3 or Above After Baseline | Platelets: Grade 3 | 0 Participants |
| M72/AS01E | Number of Participants With Clinically Significant Hematology Assessments of Grade 3 or Above After Baseline | Platelets: Grade 4 | 0 Participants |
| M72/AS01E | Number of Participants With Clinically Significant Hematology Assessments of Grade 3 or Above After Baseline | Hemoglobin: Grade 3 | 0 Participants |
| M72/AS01E | Number of Participants With Clinically Significant Hematology Assessments of Grade 3 or Above After Baseline | Hemoglobin: Grade 4 | 0 Participants |
| M72/AS01E | Number of Participants With Clinically Significant Hematology Assessments of Grade 3 or Above After Baseline | Leukocytes: Grade 3 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Hematology Assessments of Grade 3 or Above After Baseline | Hemoglobin: Grade 4 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Hematology Assessments of Grade 3 or Above After Baseline | Leukocytes: Grade 4 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Hematology Assessments of Grade 3 or Above After Baseline | Hemoglobin: Grade 3 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Hematology Assessments of Grade 3 or Above After Baseline | Platelets: Grade 3 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Hematology Assessments of Grade 3 or Above After Baseline | Leukocytes: Grade 3 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Hematology Assessments of Grade 3 or Above After Baseline | Platelets: Grade 4 | 0 Participants |
Secondary
Number of Participants With Potential Immune-mediated Diseases (pIMDs)
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. pIMDs are a subset of AEs that included autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology. Number of Participants With Potential Immune-mediated Diseases (pIMDs) has been presented
Time frame: Up to Day 390
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| M72/AS01E | Number of Participants With Potential Immune-mediated Diseases (pIMDs) | 0 Participants |
| Placebo | Number of Participants With Potential Immune-mediated Diseases (pIMDs) | 0 Participants |
Secondary
Percentage of M72-specific CD4+ T Cells and CD8+ T Cells Exhibiting Cytokine Response With Background Subtracted
Blood samples were analyzed for M72-specific CD4+ and CD8+ T-cells exhibiting cytokine response (IFN-gamma and/or IL-2) with background subtracted. Baseline is defined as the last non-missing assessment (scheduled or unscheduled) prior to the first study vaccination.
Time frame: At Baseline, Day 57, and Day 390
Population: Per-Protocol for Cellular Immunogenicity Population comprises all participants in Per-Protocol population randomly selected to have immunogenicity assays performed. Only those participants with data available at specified timepoints has been presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| M72/AS01E | Percentage of M72-specific CD4+ T Cells and CD8+ T Cells Exhibiting Cytokine Response With Background Subtracted | CD4+ at Baseline | 0.062 Percentage of cells | Standard Deviation 0.506 |
| M72/AS01E | Percentage of M72-specific CD4+ T Cells and CD8+ T Cells Exhibiting Cytokine Response With Background Subtracted | CD4+ at Day 57 | 0.534 Percentage of cells | Standard Deviation 0.556 |
| M72/AS01E | Percentage of M72-specific CD4+ T Cells and CD8+ T Cells Exhibiting Cytokine Response With Background Subtracted | CD4+ at Day 390 | 0.339 Percentage of cells | Standard Deviation 0.375 |
| M72/AS01E | Percentage of M72-specific CD4+ T Cells and CD8+ T Cells Exhibiting Cytokine Response With Background Subtracted | CD8+ at Baseline | 0.071 Percentage of cells | Standard Deviation 0.248 |
| M72/AS01E | Percentage of M72-specific CD4+ T Cells and CD8+ T Cells Exhibiting Cytokine Response With Background Subtracted | CD8+ at Day 57 | 0.092 Percentage of cells | Standard Deviation 0.272 |
| M72/AS01E | Percentage of M72-specific CD4+ T Cells and CD8+ T Cells Exhibiting Cytokine Response With Background Subtracted | CD8+ at Day 390 | 0.090 Percentage of cells | Standard Deviation 0.328 |
| Placebo | Percentage of M72-specific CD4+ T Cells and CD8+ T Cells Exhibiting Cytokine Response With Background Subtracted | CD8+ at Day 57 | -0.007 Percentage of cells | Standard Deviation 0.042 |
| Placebo | Percentage of M72-specific CD4+ T Cells and CD8+ T Cells Exhibiting Cytokine Response With Background Subtracted | CD4+ at Baseline | 0.067 Percentage of cells | Standard Deviation 0.167 |
| Placebo | Percentage of M72-specific CD4+ T Cells and CD8+ T Cells Exhibiting Cytokine Response With Background Subtracted | CD8+ at Baseline | 0.092 Percentage of cells | Standard Deviation 0.353 |
| Placebo | Percentage of M72-specific CD4+ T Cells and CD8+ T Cells Exhibiting Cytokine Response With Background Subtracted | CD4+ at Day 57 | 0.014 Percentage of cells | Standard Deviation 0.096 |
| Placebo | Percentage of M72-specific CD4+ T Cells and CD8+ T Cells Exhibiting Cytokine Response With Background Subtracted | CD8+ at Day 390 | 0.058 Percentage of cells | Standard Deviation 0.371 |
| Placebo | Percentage of M72-specific CD4+ T Cells and CD8+ T Cells Exhibiting Cytokine Response With Background Subtracted | CD4+ at Day 390 | 0.047 Percentage of cells | Standard Deviation 0.169 |