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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
402
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
Participants will receive an intramuscular dose of saline (0.9% NaCl), on Day 1 and Day 29
Wits RHI
Johannesburg, Gauteng, South Africa
Ekhaya VAC
Cape Town, Khayelitsha, South Africa
CAPRISA
Durban, KwaZulu-Natal, South Africa
The Aurum Institute
Klerksdorp, North West, South Africa
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)
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)
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
Number of Participants With Unsolicited AEs Through 28 Days Post Dose 2 of Study Intervention
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Desmond Tutu HIV Foundation
Cape Town, Western Cape, South Africa
SATVI
Worcester, Western Cape, South Africa
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
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
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
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
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
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
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
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