Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
ID93+ GLA-SE vaccine · 1 trial · 1 indication
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.
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.
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.
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).
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).
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.
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.
| Arm | Type | Description |
|---|---|---|
| Group 1/Phase 2a: ID93+GLA-SE 4 months and 6 months after start of TB treatment | ACTIVE_COMPARATOR | Participants will be enrolled at approximately 4 months after the start of TB treatment, entering the study directly into Step 2, and will be randomized to receive ID93 + GLA-SE immediately. They have no Step 1 observation period from the start of SOC TB treatment to randomization. |
| Group 2/Phase 2a: ID93+GLA-SE 3 months and 5 months after start of TB treatment | ACTIVE_COMPARATOR | Participants will be enrolled at approximately 3 months after the start of TB treatment, entering the study directly into Step 2, and will be randomized to receive ID93 + GLA-SE or placebo immediately. They have no Step 1 observation period from the start of SOC TB treatment to randomization. |
| Group 3/Phase 2a: ID93+GLA-SE 2 months and 4 months after start of TB treatment | ACTIVE_COMPARATOR | Participants will enter the study within approximately 7 days after starting TB treatment in Step 1, which is an observation period between the start of SOC TB treatment until entering Step 2. In Step 2 they will be randomized to ID93 + GLA-SE at 2 months after study entry/start of TB treatment. |
| Group 4/Phase 2a: ID93+GLA-SE 1 month and 3 months after start of TB treatment | ACTIVE_COMPARATOR | Participants will enter the study within approximately 7 days after starting TB treatment in Step 1, which is an observation period between the start of SOC TB treatment until entering Step 2. In Step 2 they will be randomized to ID93 + GLA-SE 1 month after study entry/start of TB treatment. |
| Group 5/Phase 2b: ID93+GLA-SE schedule based on Group 3 and 4 safety and immunogenicity data | ACTIVE_COMPARATOR | Participants will enter the study within approximately 7 days after starting TB treatment in Step 1, which is an observation period between the start of SOC TB treatment until entering Step 2. The vaccination schedule will be selected from either the Group 3 or Group 4 schedule, following a review of the safety and immunogenicity data after the last participant in Group 4 receives the second vaccination. If both the safety and immunogenicity criteria are met, the Group 4 schedule will be selected and Group 5 will include Group 4 participants. If Group 4 fails to meet both the safety and immunogenicity criteria, the Group 3 vaccination schedule will be selected and Group 5 will include Group 3 participants. If safety and immunogenicity criteria are not met in either Group 3 or 4, then enrollment to Group 5 will not proceed and the phase 2b component of the study will not be undertaken. |
| Group 1/Phase 2a: Placebo vaccine 4 months and 6 months after start of TB treatment | PLACEBO_COMPARATOR | Participants will be enrolled at approximately 4 months after the start of TB treatment, entering the study directly into Step 2, and will be randomized to receive placebo immediately. They have no Step 1 observation period from the start of SOC TB treatment to randomization. |
| Group 2/Phase 2a: Placebo vaccine 3 months and 5 months after start of TB treatment | PLACEBO_COMPARATOR | Participants will be enrolled at approximately 3 months after the start of TB treatment, entering the study directly into Step 2, and will be randomized to receive placebo immediately. They have no Step 1 observation period from the start of SOC TB treatment to randomization. |
| Group 3/Phase 2a: Placebo vaccine 2 months and 4 months after start of TB treatment | PLACEBO_COMPARATOR | Participants will enter the study within approximately 7 days after starting TB treatment in Step 1, which is an observation period between the start of SOC TB treatment until entering Step 2. In Step 2 they will be randomized to placebo at 2 months after study entry/start of TB treatment. |
| Group 4/Phase 2a: Placebo vaccine 1 month and 3 months after start of TB treatment | PLACEBO_COMPARATOR | Participants will enter the study within approximately 7 days after starting TB treatment in Step 1, which is an observation period between the start of SOC TB treatment until entering Step 2. In Step 2 they will be randomized to ID93 + GLA-SE or placebo 1 month after study entry/start of TB treatment. |
| Group 5/Phase 2b: Placebo vaccine schedule based on Group 3 and 4 safety and immunogenicity data | PLACEBO_COMPARATOR | Participants will enter the study within approximately 7 days after starting TB treatment in Step 1, which is an observation period between the start of SOC TB treatment until entering Step 2. The vaccination schedule will be selected from either the Group 3 or Group 4 schedule, following a review of the safety and immunogenicity data after the last participant in Group 4 receives the second vaccination. If both the safety and immunogenicity criteria are met, the Group 4 schedule will be selected and Group 5 will include Group 4 participants. If Group 4 fails to meet both the safety and immunogenicity criteria, the Group 3 vaccination schedule will be selected and Group 5 will include Group 3 participants. If safety and immunogenicity criteria are not met in either Group 3 or 4, then enrollment to Group 5 will not proceed and the phase 2b component of the study will not be undertaken. |
| Name | Type | Description |
|---|---|---|
| ID93 + GLA-SE vaccine | BIOLOGICAL | 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. |
| Placebo vaccine | BIOLOGICAL | 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. |
Inclusion Criteria Groups 1-5: * 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 enz...