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.
Bacteriologically confirmed rifampicin-susceptible pulmonary TB using phenotypic drug susceptibility testing or a World Health Organization (WHO) approved molecular test.
Documentation of HIV status as positive or negative by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit.
For individuals with HIV, on locally approved HIV ART for at least 90 days prior to entry.
For individuals with HIV, CD4+ cell count ≥250 cells/mm3 obtained within 90 days prior to entry at any network-approved non-US laboratory that is DAIDS IQA certified.
Documented M.tb resistance to isoniazid.
Breastfeeding.
Any previous episode of TB treatment.
TB treatment with a local non-standard first-line TB treatment regimen at time of enrollment.
Sequential
ID93 + GLA-SE vaccine
Biological/VaccineAt 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.
Placebo vaccine
Biological/VaccineAt 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.
10
Treatment groupsSee each treatment group below.
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.
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.
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.
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).
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)
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.
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.
Immunogenicity (Phase 2a): Differential leukocyte count and immunophenotype
Evaluated in cryopreserved ex vivo whole blood by flow cytometry in Groups 1-4
Click on the lead sponsor to view all of their trials.
Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
Lead sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
