Tuberculosis
Conditions
Interventions
TB vaccination
TB Vaccination
Placebo
Sponsors
National Institute of Allergy andInfectious Diseases
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age of 18 years or older at study entry • Bacteriologically confirmed rifampicin-susceptible pulmonary TB using phenotypic drug susceptibility testing or a WHO approved molecular test. • Documented duration of local SOC TB treatment prior to entry into Step 2 (study entry) for Group 1 of between 113 and 127 days (i.e., approximately 4 months of TB treatment) and Group 2 of between 83 and 97 days (i.e., approximately 3 months of TB treatment) • Documentation of HIV negative status by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit or a confirmed HIV-1 infection • 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 • For individuals with HIV, HIV-1 RNA below the limit of detection obtained within 90 days prior to entry • Laboratory values within the indicated ranges in the protocol, obtained within 14 days prior to entry • For candidates who are able to become pregnant, negative serum or urine pregnancy test at or within 7 days prior to entry • Candidates who are able to become pregnant (see definitions in section 4.1.9) must agree to use an adequate method of contraception (barrier methods or non-hormonal intrauterine device) or abstain from sexual activity that could lead to pregnancy from at least 21 days prior to the first scheduled vaccination through 90 days after last dose. • Ability and willingness of candidate to provide informed consent
Exclusion criteria
Exclusion criteria: • 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 • Receipt of any investigational drug or any investigational non-TB vaccine since start of TB treatment • Any prior receipt of any investigational TB vaccine • Known allergy or any hypersensitivity to any components of study product or their formulation or any vaccination • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements • History of moderate to serious autoimmune disease requiring immunosuppressive therapy • Receipt of immunosuppressive medications from start of TB treatment except Corticosteroid nasal spray, Inhaled corticosteroids, topical corticosteroids for mild, uncomplicated dermatologic condition, A single course of oral/parenteral prednisone or equivalent at doses 8% • Bleeding disorder (e.g., factor deficiency, coagulopathy, platelet disorder requiring special precautions). • Seizure disorder, including either of the following within the previous 3 years: Seizure(s) or use of medications to prevent or treat seizure(s) • Acute or serious illness, including COVID-19, requiring systemic treatment and/or hospitalization from start of TB treatment, other than for pulmonary TB • Suspected or documented TB involving the CNS, renal TB or TB pericarditis, or current extrapulmonary TB involving other organ systems • Contraindication to intramuscular injection in both deltoids
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efficacy (Phase 2b): 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) through to 420, 450, 480 and 510 days after entering Step 2 in Groups 1, 2, 3 (and 5), and 4 (and 5), which is approximately 18 months after start of standard TB treatment in all groups;1.Safety (Phase 2a and Phase 2b): Vaccine-related serious adverse event (SAE) at any time after first dose of ID93 + GLA-SE. ;Safety (Phase 2a and Phase 2b): Grade =3 vaccine-related unsolicited adverse event (AE) within 28 days after either dose of study product;Safety (Phase 2a and Phase 2b): Grade =3 local or systemic reactogenicity AE within 7 days after either dose of study product;Cellular immunogenicity (Phase 2a and Phase 2b): ID93-specific CD4+ T cell response 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 IFN?/IL2/TNFa/CD154. This will be evaluated as a binary outcome (i.e., response or no response). | — |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy (Phase 2a and 2b): Proportion of participants with quantifiable RS ratio at Step 2, Days 60, 90, 120, and 150 in Groups 1, 2, 3 (and 5), and 4 (and 5), respectively, which is approximately 6 months after start of standard TB treatment.;Cellular immunogenicity (Phase 2a): ID93-specific CD4+ T cell response through 12 months post second dose of vaccination per SOE for PBMC collection, Measured by ICS and flow cytometry;Humoral immunogenicity (Phase 2a): ID93-specific IgG response rate (BAMA response criteria: MFI* >3 x [MFI* at pre-vaccine] and MFI* >100) through 12 months post second dose of study product per SOE for serum collection;Immunogenicity (Phase 2a): Differential leukocyte count and immunophenotype in cryopreserved ex vivo whole blood by flow cytometry at Step 2, Days 0, 1, 15, and V+15/ D75, in Groups 1-4;Immunogenicity (Phase 2a): Measurement of soluble proinflammatory mediators in serum in Groups 1-4 at Step 2, Days 0, 1, 15, and V+15/ Day 75 | — |
Countries
Kenya
Contacts
Public ContactCharles Kilel
Community Liaison at KEMRI Walter Reed
Outcome results
None listed