Overview
Trial of Novel Regimens for the Treatment of Pulmonary Tuberculosis
Status:
Not yet recruiting
Not yet recruiting
Trial end date:
2026-04-14
2026-04-14
Target enrollment:
0
0
Participant gender:
All
All
Summary
A5409/RAD-TB is an adaptive Phase 2 randomized, controlled, open-label, dose-ranging, platform protocol to evaluate the safety and efficacy of multidrug regimens for the treatment of adults with drug-susceptible pulmonary tuberculosis (TB). A5409 hypothesizes that novel regimens for the treatment of pulmonary tuberculosis will result in superior early efficacy, as determined by longitudinal mycobacteria growth indicator tube (MGIT) liquid culture time to positivity (TTP) measurements over the first 6 weeks of treatment, and will have acceptable safety and tolerability over 8 weeks of treatment relative to standard of care [(SOC) isoniazid/rifampicin/pyrazinamide/ethambutol (HRZE)]. The study will run for 52 weeks, inclusive of 26 weeks of TB treatment comprised of 8 weeks of experimental or SOC treatment (based on treatment arm assignment) followed by 18 weeks of SOC treatment with 45 participants in each experimental treatment arm and at least 90 participants in the SOC arm.Phase:
Phase 2Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
National Institute of Allergy and Infectious Diseases (NIAID)Collaborator:
TB AllianceTreatments:
Bedaquiline
Ethambutol
Isoniazid
Linezolid
Oxazolidinones
Pyrazinamide
Rifampin
Criteria
Inclusion Criteria:1. Pulmonary TB (among individuals either without history of prior TB treatment or with
history of TB treatment more than 5 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" 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
- 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), 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-US 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 ≥9.5 g/dL for individuals assigned to female sex at birth and ≥10.0
g/dL for individuals assigned to male sex at birth
- Platelet count ≥100,000/mm^3
- Negative for hepatitis B core antibody (HBcAb) total, 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 individuals assigned to female sex at birth and 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-US laboratory or clinic that operates in accordance
with GCLP and participates in appropriate external quality assurance programs.
Individuals assigned to female sex at birth, 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)
9. For individuals who are assigned male sex at birth 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.
10. For individuals assigned male sex at birth with pregnant partners, willingness to use
condoms during vaginal intercourse while on study and for 90 days after experimental
treatment discontinuation.
11. For individuals assigned male sex at birth, 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.