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New multi-drug regimens for pulmonary tuberculosis

A Phase 2 Randomized, Adaptive, Dose-Ranging, Open-Label Trial of Novel Regimens for the Treatment of Pulmonary Tuberculosis

Phase 2 Interventional National Institute of Allergy and Infectious Diseases (NIAID) · NCT06192160

This trial will test new multi-drug treatment combinations to see if they clear bacteria faster and are as safe as the standard 6-month regimen for adults with drug-susceptible pulmonary tuberculosis.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment315 (estimated)
Ages18 Years and up
SexAll
SponsorNational Institute of Allergy and Infectious Diseases (NIAID) NIH
Locations29 sites (Gaborone and 28 other locations)
Trial IDNCT06192160 on ClinicalTrials.gov

What this trial studies

A5409/RAD-TB is an adaptive Phase 2, randomized, controlled, open-label, dose-ranging platform that compares experimental multidrug regimens to standard HRZE in adults with drug-susceptible pulmonary TB. Early efficacy is measured by longitudinal MGIT liquid culture time to positivity (TTP) over the first 6 weeks, with safety and tolerability monitored over 8 weeks of study treatment. Participants receive 8 weeks on the assigned experimental or SOC arm followed by 18 weeks of SOC continuation treatment, for a total treatment period of 26 weeks and study follow-up to 52 weeks. Each experimental arm enrolls about 45 participants with at least 90 participants in the control/comparator groups within the adaptive platform.

Who should consider this trial

Good fit: Adults with pulmonary TB who have a recent Xpert MTB/RIF Ultra result showing medium or high bacterial load and documented isoniazid and rifampicin susceptibility within 7 days of enrollment are appropriate candidates.

Not a fit: People with rifampicin- or isoniazid-resistant TB, extrapulmonary-only disease, or who lack the required molecular susceptibility testing are unlikely to benefit from these regimens.

Why it matters

Potential benefit: If successful, these regimens could speed early bacterial clearance and provide safer or more effective options than the current standard 6-month treatment.

How similar studies have performed: Other phase 2 and phase 3 trials of novel multidrug combinations, including bedaquiline-containing regimens, have shown promising early results but have not yet replaced the standard HRZE regimen broadly.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. Pulmonary TB (among individuals either without history of prior TB treatment or with history of TB treatment completed more than 2 years prior to study entry), identified within 7 days prior to study entry by at least one sputum specimen positive for Mtb by Xpert. Semiquantitative Mtb results of "medium" or "high" from Xpert MTB/RIF Ultra are required.
2. Pulmonary TB with documented INH susceptibility (by Line Probe Assay (LPA) or Xpert MTB/XDR or other validated molecular test) and with documented RIF susceptibility (by LPA or Xpert MTB/RIF or Xpert MTB/RIF Ultra or other validated molecular test) within 7 days prior to study entry.
3. Documentation of HIV-1 infection status, as below:

   Presence or absence of HIV-1 infection, as documented by:
   * Any licensed rapid HIV test or HIV-1 enzyme or chemiluminescence immunoassay (E/CIA) test kit, any time prior to study entry. AND for a positive result confirmation 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), or
   * HIV-1 antigen, or
   * Plasma HIV-1 RNA viral load, or
   * A licensed Western blot
4. For individuals with HIV: CD4+ cell count ≥100 cells/mm3 based on testing performed within 30 days prior to study entry.
5. For individuals with HIV: Currently being treated with dolutegravir-based antiretroviral therapy (ART), or plan to initiate dolutegravir-based ART at or before study week 8.
6. Individuals age ≥18 years.
7. The following laboratory values obtained within 7 days prior to study entry at any network-approved non-U.S. laboratory that operates in accordance with Good Clinical Laboratory Practices (GCLP) and participates in appropriate external quality assurance programs:

   * Serum or plasma alanine aminotransferase (ALT) ≤3 times the upper limit of normal (ULN)
   * Serum or plasma total bilirubin ≤2 times ULN
   * Serum or plasma creatinine ≤2 times ULN
   * Serum or plasma potassium ≥3.5 mEq/L
   * Serum or plasma magnesium ≥1.0 mEq/L (≥0.500 mmol/L)
   * Absolute neutrophil count (ANC) ≥1500/mm\^3
   * Hemoglobin ≥9.0 g/dL
   * Platelet count ≥100,000/mm\^3
   * Negative for, hepatitis B surface antigen (HBsAg)
   * Negative for hepatitis C virus (HCV) antibody (or if HCV antibody positive, must have a negative HCV PCR)
8. For female study candidates who are of reproductive potential, negative pregnancy test (urine HCG or serum β-HCG) within 3 days (72 hours) prior to entry by any network-approved non-U.S. laboratory or clinic that operates in accordance with GCLP and participates in appropriate external quality assurance programs.

   Females who are of reproductive potential and who participate in sexual activity that could lead to pregnancy must agree to use at least two of the following forms of birth control while receiving TB study medications and for 12 months after stopping study medications:
   * Male or female condoms
   * Diaphragm or cervical cap (with spermicide, if available)
   * Intrauterine device (IUD) or intrauterine system (IUS)
   * Hormone-based birth control (e.g., oral contraceptives, Depo-Provera, NuvaRing, implants)

   Female study candidates who are of reproductive potential, but who abstain from sexual activity that could lead to pregnancy require no additional contraception.

   Female study candidates who are not of reproductive potential are eligible without requiring the use of contraceptives. Self-reported history is acceptable documentation of menopause (i.e., at least 1 year amenorrheic), hysterectomy, bilateral oophorectomy, or bilateral tubal ligation; these candidates are all considered not of reproductive potential.
9. For male study candidates who engage in sexual activity that may lead to pregnancy in their partner must agree to either remain abstinent or use male contraceptives. They are also strongly advised to inform their non-pregnant sexual partners of reproductive potential to use effective contraceptives while the individual is on study and for 90 days after experimental treatment discontinuation.

   For male study candidates who have undergone successful vasectomy with documented azoospermia or have documented azoospermia for any other reason, are eligible without requiring the use of contraceptives.
10. For male study candidates with pregnant partners, willingness to use condoms during vaginal intercourse while on study and for 90 days after experimental treatment discontinuation.
11. For male study candidates, willingness to refrain from sperm donation while on study and for 90 days after experimental treatment discontinuation.
12. Documentation of Karnofsky performance score ≥60 obtained within 14 days prior to study entry.
13. Chest x-ray obtained within 14 days prior to study entry.
14. A verifiable address or residence readily accessible for visiting, and willingness to inform the study team of any change of address during study treatment and follow-up period.
15. Ability and willingness of individual to provide informed consent.

Exclusion Criteria:

1. More than cumulative 7 days of treatment directed against active TB for the current TB episode in the 60 days preceding study entry.
2. Current extrapulmonary TB, in the opinion of the investigator.
3. QTcF interval \>450 ms within 7 days prior to study entry.
4. History of or ongoing heart failure.
5. Personal or family history of congenital QT prolongation.
6. History of known, untreated, ongoing hypothyroidism.
7. History of or ongoing bradyarrhythmia.
8. History of torsades de pointes.
9. Current Grade 2 or higher peripheral neuropathy.
10. Other medical conditions (e.g., diabetes, liver or kidney disease, blood disorders, chronic diarrhea), in the opinion of the site investigator, in which the current clinical condition of the participant is likely to prejudice the response to, or assessment of, treatment.
11. Pregnant or breastfeeding or planning to become pregnant within the next 12 months.
12. Weight \<35 kg.
13. Unable to take oral medications.
14. Taking any of prohibited medications.
15. Known allergy/sensitivity or any hypersensitivity to components of investigational agents or their formulation.
16. Active drug or alcohol use or dependence; or mental illness (e.g., major depression) that, in the opinion of the site investigator, would interfere with adherence to study requirements.
17. Taking an investigational drug or vaccine within 30 or more days prior to study entry.

Where this trial is running

Gaborone and 28 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Pulmonary Tuberculosis
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.