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Therapeutic ID93 + GLA-SE Vaccination in Participants with Rifampicin-Susceptible Pulmonary TB

A

Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

Status and phase

Begins enrollment this month
Phase 2

Conditions

Tuberculosis, Pulmonary

Treatments

Biological: ID93 + GLA-SE vaccine
Biological: Placebo vaccine

Study type

Interventional

Funder types

NETWORK
NIH

Identifiers

NCT06205589
ACTG A5397
UM1AI068636 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Enrollment

1,500 estimated patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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 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.

  • For individuals with HIV, HIV-1 RNA below the limit of detection obtained within 90 days prior to entry by any network-approved laboratory outside the US that operates in accordance with Good Clinical Laboratory Practices (GCLP) and participates in appropriate external quality assurance programs.

  • Laboratory values within the indicated ranges, obtained within 14 days prior to entry by any network-approved laboratory outside the US that operates in accordance with GCLP and participates in appropriate external quality assurance programs.

    • Absolute neutrophil count (ANC) ≥800 cells/mm3
    • Hemoglobin ≥8.5 g/dL for candidates assigned female sex at birth and >9.0 g/dL for candidates assigned male sex at birth
    • Platelet count ≥100,000/mm3
    • Serum creatinine ≤1.5 X upper limit of normal (ULN)
    • AST (SGOT), ALT (SGPT), and alkaline phosphatase, ≤2.5 X ULN
    • Total bilirubin ≤2 X ULN
  • For candidates who are able to become pregnant, negative serum or urine pregnancy test at or within 7 days prior to entry by any network-approved laboratory or clinic outside the US that operates in accordance with GCLP and participates in appropriate external quality assurance programs.

  • Candidates who are able to become pregnant 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.

  • Candidates assigned female sex at birth (AFAB) must agree to not seek pregnancy through alternative methods, such as oocyte retrieval, artificial insemination, or in vitro fertilization, from at least 21 days prior to the first scheduled vaccination through 90 days after last dose.

  • For candidates who are not of child-bearing potential, acceptable documentation (written documentation or oral communication from a clinician or clinician's staff documented in source documents: physician report/letter, operative report or other source documentation in the candidate record, discharge summary, laboratory report, etc.) of hysterectomy and bilateral oophorectomy, tubal ligation, tubal micro-inserts, vasectomy, or menopause.

  • Ability and willingness of candidate to provide informed consent.

Inclusion Criteria Groups 1 and 2 [Step 2]:

  • 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)

Inclusion Criteria, Groups 3, 4, and 5 [Step 1]:

  • Initiation of local SOC TB treatment within 7 days prior to entry into Step 1 (Study entry).

Exclusion Criteria Groups 1-5:

  • 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 (except as noted below) from start of TB treatment.

    • 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.
  • 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.

  • 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.

  • Receipt of immunoglobulin or blood-derived products within 90 days prior to entry.

  • History of angioedema, or anaphylaxis, except as noted.

  • History of generalized urticaria within past 5 years.

  • Malignancy, except as noted.

  • Daily (current) use of a short-acting rescue inhaler (e.g., a beta 2 agonist).

  • Within the previous year, exacerbation of asthma symptoms requiring emergency care, urgent care, hospitalization, or intubation.

  • Uncontrolled diabetes mellitus type 1 or type 2, defined as Hemoglobin A1c (HbA1C) >7%.

  • 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)
    • 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.

  • Documentation of clinically significant (as judged by the site investigator) active infections (including HIV-related opportunistic infections) other than TB and HIV requiring treatment within 30 days prior to entry.

  • Evidence of clinically significant disease (as judged by the site investigator) or any other abnormalities (other than the indication being studied) that would interfere with study product, procedures, or interpretation of study outcome data, or otherwise interfere with achieving the study objectives.

  • Suspected or documented TB involving the central nervous system, renal TB or TB pericarditis, or current extrapulmonary TB involving other organ systems that might interfere with study product or procedures, as judged by the site investigator.

  • Contraindication to intramuscular injection in both deltoids.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Sequential Assignment

Masking

Double Blind

1,500 participants in 10 patient groups, including a placebo group

Group 1/Phase 2a: ID93+GLA-SE 4 months and 6 months after start of TB treatment
Active Comparator group
Description:
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.
Treatment:
Biological: ID93 + GLA-SE vaccine
Group 2/Phase 2a: ID93+GLA-SE 3 months and 5 months after start of TB treatment
Active Comparator group
Description:
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.
Treatment:
Biological: ID93 + GLA-SE vaccine
Group 3/Phase 2a: ID93+GLA-SE 2 months and 4 months after start of TB treatment
Active Comparator group
Description:
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.
Treatment:
Biological: ID93 + GLA-SE vaccine
Group 4/Phase 2a: ID93+GLA-SE 1 month and 3 months after start of TB treatment
Active Comparator group
Description:
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.
Treatment:
Biological: ID93 + GLA-SE vaccine
Group 5/Phase 2b: ID93+GLA-SE schedule based on Group 3 and 4 safety and immunogenicity data
Active Comparator group
Description:
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.
Treatment:
Biological: ID93 + GLA-SE vaccine
Group 1/Phase 2a: Placebo vaccine 4 months and 6 months after start of TB treatment
Placebo Comparator group
Description:
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.
Treatment:
Biological: Placebo vaccine
Group 2/Phase 2a: Placebo vaccine 3 months and 5 months after start of TB treatment
Placebo Comparator group
Description:
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.
Treatment:
Biological: Placebo vaccine
Group 3/Phase 2a: Placebo vaccine 2 months and 4 months after start of TB treatment
Placebo Comparator group
Description:
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.
Treatment:
Biological: Placebo vaccine
Group 4/Phase 2a: Placebo vaccine 1 month and 3 months after start of TB treatment
Placebo Comparator group
Description:
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.
Treatment:
Biological: Placebo vaccine
Group 5/Phase 2b: Placebo vaccine schedule based on Group 3 and 4 safety and immunogenicity data
Placebo Comparator group
Description:
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.
Treatment:
Biological: Placebo vaccine

Trial contacts and locations

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Central trial contact

ACTG CT.gov Coordinator

Data sourced from clinicaltrials.gov

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