A Phase 2a/2b Study Evaluating Safety, Immunogenicity, and Therapeutic Efficacy of ID93 + GLA-SE Vaccination in Participants With Rifampicin-Susceptible Pulmonary TB
Overview
- Phase
- Phase 2
- Intervention
- ID93 + GLA-SE vaccine
- Conditions
- Tuberculosis, Pulmonary
- Sponsor
- Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
- Enrollment
- 1500
- Primary Endpoint
- 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
- Status
- Not yet recruiting
- Last Updated
- 5 months ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Group 1/Phase 2a: ID93+GLA-SE 4 months and 6 months after start of TB treatment
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.
Intervention: ID93 + GLA-SE vaccine
Group 2/Phase 2a: ID93+GLA-SE 3 months and 5 months after start of TB treatment
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.
Intervention: ID93 + GLA-SE vaccine
Group 3/Phase 2a: ID93+GLA-SE 2 months and 4 months after start of TB treatment
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.
Intervention: ID93 + GLA-SE vaccine
Group 4/Phase 2a: ID93+GLA-SE 1 month and 3 months after start of TB treatment
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.
Intervention: ID93 + GLA-SE vaccine
Group 5/Phase 2b: ID93+GLA-SE schedule based on Group 3 and 4 safety and immunogenicity data
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.
Intervention: ID93 + GLA-SE vaccine
Group 1/Phase 2a: Placebo vaccine 4 months and 6 months after start of TB treatment
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.
Intervention: Placebo vaccine
Group 2/Phase 2a: Placebo vaccine 3 months and 5 months after start of TB treatment
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.
Intervention: Placebo vaccine
Group 3/Phase 2a: Placebo vaccine 2 months and 4 months after start of TB treatment
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.
Intervention: Placebo vaccine
Group 4/Phase 2a: Placebo vaccine 1 month and 3 months after start of TB treatment
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.
Intervention: Placebo vaccine
Group 5/Phase 2b: Placebo vaccine schedule based on Group 3 and 4 safety and immunogenicity data
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.
Intervention: Placebo vaccine
Outcomes
Primary Outcomes
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
Time Frame: Step 2, Day 75
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).
Safety (Phase 2a and Phase 2b): Vaccine-related serious adverse event (SAE)
Time Frame: From Step 2, Day 0 through to 420, 450, 480 or 510 days (approximately 18 months after start of SOC treatment)
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)
Time Frame: Within 28 days from Step 2, Day 0 or Step 2, Day 60
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
Time Frame: Within 7 days from Step 2, Day 0 or Step 2, Day 60
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
Time Frame: Step 2, Day 75
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).
Cellular immunogenicity (Phase 2a and Phase 2b): ID93-specific CD4+ T cell response magnitude relative to the negative control stimulation
Time Frame: Step 2, Day 75
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.
Efficacy (Phase 2b): Bacteriologically confirmed TB-related unfavorable outcome (treatment failure, TB recurrence, or death due to TB)
Time Frame: Step 2, Day 0 to 420, 450, 480 or 510 days (approximately 18 months after start of SOC treatment)
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.
Secondary Outcomes
- Efficacy (Phase 2a and 2b): Proportion of participants with quantifiable RS ratio(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(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): Measurement of soluble proinflammatory mediators(Step 2, Days 0, 1, 15, and 75)
- Humoral immunogenicity (Phase 2a): ID93-specific IgG response rate(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(Step 2, Days 0, 1, 15, and 75)