HIV/AIDS Tuberculosis Respiratory
Conditions
Interventions
ID93 and GLA SE
Placebo
Sponsors
National Institute of Allergy and Infectious Diseases
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 4.1 Inclusion Criteria, Groups 1 and 2 [Step 2] 4.1.1 Age =18 years at study entry. 4.1.2 Bacteriologically confirmed rifampicin-susceptible pulmonary TB using phenotypic drug susceptibility testing or a World Health Organization (WHO) approved molecular test. 4.1.3 Documented duration of local SOC TB treatment prior to entry into Step 2 (study entry) for i. Group 1 of between 113 and 127 days (i.e., approximately 4 months of TB treatment) ii. Group 2 of between 83 and 97 days (i.e., approximately 3 months of TB treatment) 4.1.4 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 as described below. Positive status by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit AND Confirmed by one of the following: • A second antibody test from different manufacturers or based on different principles and epitopes (combination antigen-antibody-based rapid tests may be used) • HIV-1 antigen • HIV-1 RNA viral load, or • A licensed Western blot NOTE A: The term “licensed” refers to a US FDA-approved kit. NOTE B: Positive results can be abstracted from the medical record to meet criteria for HIV diagnosis. WHO and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or an HIV-1 RNA viral load. 4.1.5 For individuals with HIV, on locally approved HIV ART for at least 90 days prior to entry. 4.1.6 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 4
Exclusion criteria
Exclusion criteria: 4.2 Exclusion Criteria, Groups 1 and 2 [Step 2] 4.2.1 Documented M.tb resistance to isoniazid. 4.2.2 Breastfeeding. 4.2.3 Any previous episode of TB treatment. 4.2.4 TB treatment with a local non-standard first-line TB treatment regimen at time of enrollment. NOTE: This includes drug substitutions for toxicity, change in regimen due to acquired resistance, and extension of treatment due to lack of culture conversion. 4.2.5 Receipt of any investigational drug or any investigational non-TB vaccine since start of TB treatment. 4.2.6 Any prior receipt of any investigational TB vaccine. 4.2.7 Known allergy or any hypersensitivity to any components of study product or their formulation or any vaccination. 4.2.8 Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements. 4.2.9 History of moderate to serious autoimmune disease requiring immunosuppressive therapy. 4.2.10 Receipt of immunosuppressive medications (except as noted below) from start of TB treatment. NOTE: Use of the following is NOT exclusionary • Corticosteroid nasal spray • Inhaled corticosteroids • Topical corticosteroids for mild, uncomplicated dermatologic condition • A single course of oral/parenteral prednisone or equivalent at doses <60 mg/day and for <11 days with completion at least 30 days prior to entry. 4.2.11 Receipt of Emergency Use Authorization (EUA)/Emergency Use Listing (EUL) or licensed live attenuated vaccines (e.g., measles, mumps, and rubella [MMR], oral polio vaccine [OPV], varicella, yellow fever, live attenuated influenza vaccine, live attenuated COVID-19 vaccine) within 30 days prior to entry. 4.2.12 Receipt of any EUA/EUL or licensed vaccines that are not live attenuated vaccines (e.g., tetanus, pneumococcal, Hepatitis A or B, not live attenuated COVID-19 vaccine) within 14 days prior to entry. 4.2.13 Receipt of immunoglobulin or blood-derived products within 90 days prior to entry. 4.2.14 History
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1.1Primary Objectives 1.1.1Phase 2a and 2b: To evaluate safety of a two-dose ID93 + GLA-SE vaccine regimen administered 60 days apart on Step 2, Days 0 and 60, with TB treatment administered, at approximately: 1.1.1.1Months 4 and 6 after start of TB treatment (Group 1) 1.1.1.2Months 3 and 5 after start of TB treatment (Group 2) 1.1.1.3Months 2 and 4 after start of TB treatment (Group 3 and Group 5, if this vaccination schedule is adopted for Group 5) 1.1.1.4Months 1 and 3 after start of TB treatment (Group 4 and Group 5, if this vaccination schedule is adopted for Group 5) 1.1.2Phase 2a and 2b: To determine if therapeutic vaccination with ID93 + GLA-SE will increase the magnitude of vaccine-specific cellular responses compared to placebo at 2 weeks post second dose of study product. 1.1.3Phase 2b: To estimate the effect of the vaccine on the proportion of participants with TB-related unfavorable outcomes (treatment failure, TB recurrence, or death due to TB) at Day 540 after study entry, which is approximately 18 months after start of TB treatment (Group 5 combined with either Group 3 or Group 4, depending on which vaccination schedule is selected for Group 5). | — |
Secondary
| Measure | Time frame |
|---|---|
| 1.2 Secondary Objectives 1.2.1 Phase 2a and 2b: To evaluate the proportion of participants with a quantifiable RS ratio after therapeutic vaccination with ID93 + GLA-SE compared to placebo. 1.2.2 Phase 2a: To evaluate the kinetics of cellular immunogenicity of ID93 + GLA-SE through 12 months post second dose of study product. 1.2.3 Phase 2a: To evaluate the kinetics of humoral immunogenicity of ID93 + GLA-SE through 12 months post second dose of study product. 1.2.4 Phase 2a: To evaluate innate immune changes in response to ID93 + GLA-SE through 2 weeks post second dose of study product. 1.2.5 Phase 2b: To compare therapeutic vaccination with ID93 + GLA-SE, to placebo, with respect to the proportion of participants with TB-related unfavorable outcomes at 540 days after study entry, which is approximately 18 months after start of TB treatment, in subgroups defined by: Hard-to-treat phenotype and not hard-to-treat phenotype, where hard-to-treat phenotype is defined as smear Grade =3 and cavitary disease on chest radiograph at TB diagnosis. | — |
Countries
Uganda
Contacts
Public ContactLaura Moran
ACTG Clinical Trial Specialist
Outcome results
None listed