This study is being done to test an experimental study vaccine compared to a placebo. The experimental study vaccine is called ID93 + GLA-SE. ID93 + GLA-SE has been used in humans in research but has not been approved for use in medical care. This study will be the first to test ID93 + GLA-SE in people living with HIV (PLWH). The injections during the study will be given to different groups of participants while they are using standard TB treatment. One of the research questions is to understand the differences in immune system responses depending on the timing of giving the injections after people begin taking standard TB treatment. Researchers also want to continue to look at whether the study vaccine is safe when tested in a larger group of people, and if getting the study vaccine in addition to standard TB treatment can help to lower the number of poor TB outcomes that people might have.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
1,500
At Step 2 entry, participants will receive one 0.5 mL injection of ID93 + GLA-SE administered intramuscularly (IM) at the Step 2, Day 0 visit and at the Step 2, Day 60 visit per the dosing schedule within the respective group/arm.
At Step 2 entry, participants will receive one placebo injection (sodium Chloride, 0.9%) administered intramuscularly (IM) at the Step 2, Day 0 visit and at the Step 2, Day 60 visit per the dosing schedule within the respective group/arm.
Safety (Phase 2a and Phase 2b): Vaccine-related serious adverse event (SAE)
Vaccine-related serious adverse event (SAE) at any time after first dose of ID93 + GLA-SE. The relationship to study product will be determined by the site investigator and assessed as "related" or "unrelated". Only SAEs reported as "related" will be included in this outcome measure.
Time frame: From Step 2, Day 0 through to 420, 450, 480 or 510 days (approximately 18 months after start of SOC treatment)
Safety (Phase 2a and Phase 2b): Grade ≥3 vaccine-related unsolicited adverse event (AE)
Grade ≥3 vaccine-related unsolicited adverse event (AE) within 28 days after either dose of study product. An unsolicited AE is defined as an AE other than a local or systemic reactogenicity AE. The relationship to study product will be determined by the site investigator and assessed as "related" or "unrelated." Only unsolicited AEs reported as "related" will be included in this outcome measure.
Time frame: Within 28 days from Step 2, Day 0 or Step 2, Day 60
Safety (Phase 2a and Phase 2b): Grade ≥3 local or systemic reactogenicity AE
o Systemic symptoms include increased body temperature, malaise and/or fatigue, myalgia, headache, chills, arthralgia, nausea, and vomiting. Local symptoms include pain and/or tenderness proximal to the injection site.
Time frame: Within 7 days from Step 2, Day 0 or Step 2, Day 60
Cellular immunogenicity (Phase 2a and Phase 2b): ID93-specific CD4+ T cell response relative to the negative control stimulation
ID93-specific CD4+ T cell response relative to the negative control stimulation (ICS response criteria: MIMOSA method) at 2 weeks post second dose of study product. CD4+ T cell response measured by ICS with magnitude indicated by cells expressing 2 of IFNγ/IL2/TNFα/CD154. MIMOSA detects responses compared to the negative control. This will be evaluated as a binary outcome (i.e., response or no response).
Time frame: Step 2, Day 75
Cellular immunogenicity (Phase 2a and Phase 2b): ID93-specific CD4+ T cell response relative to the negative control stimulation and relative to the pre-vaccine response
ID93-specific CD4+ T cell response relative to the negative control stimulation and relative to the pre-vaccine response (ICS response criteria: MIMOSA2 method) at 2 weeks post second dose of study product. CD4+ T cell response measured by ICS with magnitude indicated by cells expressing 2 of IFNγ/IL2/TNFα/CD154. MIMOSA2 detects responses compared to the negative control stimulation and the pre-vaccine response. This will be evaluated as a binary outcome (i.e., response or no response).
Time frame: Step 2, Day 75
Cellular immunogenicity (Phase 2a and Phase 2b): ID93-specific CD4+ T cell response magnitude relative to the negative control stimulation
ID93-specific CD4+ T cell response magnitude relative to the negative control stimulation at 2 weeks post second dose of study product. CD4+ T cell response measured by ICS with magnitude indicated by cells expressing 2 of IFNγ/IL2/TNFα/CD154. This will be evaluated as a continuous outcome.
Time frame: Step 2, Day 75
Efficacy (Phase 2b): Bacteriologically confirmed TB-related unfavorable outcome (treatment failure, TB recurrence, or death due to TB)
Bacteriologically confirmed TB-related unfavorable outcome (treatment failure, TB recurrence, or death due to TB) after receiving the first dose of study product (ID93 + GLA-SE or placebo). Bacteriological confirmation will be based on culture results from solid media and liquid media that are positive for M. tuberculosis. Culture results from the study or from outside the study (e.g., the local TB program) are acceptable.
Time frame: Step 2, Day 0 to 420, 450, 480 or 510 days (approximately 18 months after start of SOC treatment)
Efficacy (Phase 2a and 2b): Proportion of participants with quantifiable RS ratio
RS ratio will be evaluated as a binary outcome (quantifiable or not quantifiable)
Time frame: Step 2, Days 60, 90, 120, and 150 in Groups 1, 2, 3 (and 5), and 4 (and 5), respectively (approximately 6 months after start of SOC treatment)
Cellular immunogenicity (Phase 2a): ID93-specific CD4+ T cell response through 12 months post second dose of vaccination
Measured by ICS and flow cytometry. CD4+ T-cell response magnitude indicated by cells expressing 2 of IFNγ/IL2/TNFα/CD154. This will be evaluated as both a binary outcome (response or no response) and as a continuous outcome.
Time frame: Step 2, Days 0, 15, 60, 75, 120 (Group 3 only), 150 (Group 4 only), 240, 300 (Group 3 only), 330 (Group 4 only) and 420 (Group 2 will be evaluated at Day 450 rather than 420)
Humoral immunogenicity (Phase 2a): ID93-specific IgG response rate
BAMA response criteria: MFI\* \>3 x \[MFI\* at pre-vaccine\] and MFI\* \>100. This will be evaluated as both a binary outcome (i.e., response or no response) and as a continuous outcome.
Time frame: Step 2, Days 0, 15, 60, 75, 120 (Group 3 only), 150 (Group 4 only), 240, 300 (Group 3 only), 330 (Group 4 only) and 420 (Group 2 will be evaluated at Day 450 rather than 420)
Immunogenicity (Phase 2a): Differential leukocyte count and immunophenotype
Evaluated in cryopreserved ex vivo whole blood by flow cytometry in Groups 1-4
Time frame: Step 2, Days 0, 1, 15, and 75
Immunogenicity (Phase 2a): Measurement of soluble proinflammatory mediators
Evaluated in serum in Groups 1-4
Time frame: Step 2, Days 0, 1, 15, and 75
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