Pulmonary TuberculosisPhase 2RAD-TBNCT06192160
Trial of Novel Regimens for the Treatment of Pulmonary Tuberculosis
A Phase 2 study testing Isoniazid, Rifampicin and Pyrazinamide in people with Pulmonary Tuberculosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 30 sites in 14 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Tuberculosis
- What is being tested?
- Isoniazid, Rifampicin and Pyrazinamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 315 participants
- Where
- 30 sitesin 14 countries
- Study dates
- 11 Mar 2025to 3 Jan 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 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.
- 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
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- HIV-1 antigen, or
- Plasma HIV-1 RNA viral load, or
- A licensed Western blot
- For individuals with HIV: CD4+ cell count ≥100 cells/mm3 based on testing performed within 30 days prior to study entry.
- 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.
- Individuals age ≥18 years.
- 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)
- 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.
- 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.
- 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.
- For male study candidates, willingness to refrain from sperm donation while on study and for 90 days after experimental treatment discontinuation.
- Documentation of Karnofsky performance score ≥60 obtained within 14 days prior to study entry.
- Chest x-ray obtained within 14 days prior to study entry.
- 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.
- Ability and willingness of individual to provide informed consent.
Who cannot join
- More than cumulative 7 days of treatment directed against active TB for the current TB episode in the 60 days preceding study entry.
- Current extrapulmonary TB, in the opinion of the investigator.
- QTcF interval >450 ms within 7 days prior to study entry.
- History of or ongoing heart failure.
- Personal or family history of congenital QT prolongation.
- History of known, untreated, ongoing hypothyroidism.
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- History of or ongoing bradyarrhythmia.
- History of torsades de pointes.
- Current Grade 2 or higher peripheral neuropathy.
- 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.
- Pregnant or breastfeeding or planning to become pregnant within the next 12 months.
- Weight <35 kg.
- Unable to take oral medications.
- Taking any of prohibited medications.
- Known allergy/sensitivity or any hypersensitivity to components of investigational agents or their formulation.
- 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.
- Taking an investigational drug or vaccine within 30 or more days prior to study entry.
Trial locations and contacts
30 sites in 14 countries. Contact the study team or a site near you to ask about taking part.
30 sites in 14 countries
South Africa7 sites, 7 recruiting
- Recruiting
31793, South African Tuberculosis Vaccine Initiative (SATVI) CRS
Cape Town, 6850
Alida Briel, +27 23-346-5400, Libby.Briel@uct.ac.za
- Recruiting
31792, University of Cape Town Lung Institute (UCTLI) CRS
Cape Town, 7700
Tammy Vandermerwe, +27 021-4066889, tammy.vandermerwe@uct.ac.za
- Recruiting
31422, CAPRISA eThekwini CRS
Durban, 4001
Bongekile Zuma, 27-31-6550658, Bongi.zuma@caprisa.org
- Recruiting
11201, Durban International CRS
Durban, 4052
Sheleika Singh, 27-31-2611093, singh@ecarefoundation.com
- Recruiting
12301, Soweto ACTG CRS
Johannesburg, 1862
Suri Moonsamy, +27-11-989-9700, moonsamys@phru.co.za
- Recruiting
11101, Wits Helen Joseph (WITS HJH) CRS
Johannesburg, 2193
Betty Matome, +27 11-276-8800, bmatome@witshealth.co.za
- Recruiting
31684, Rustenburg CRS
Rustenburg
Nondzakazi Mnqonywa, 27-0871351550, NMnqonywa@auruminstitute.org
Thailand4 sites, 4 recruiting
- Not yet recruiting
5115, Siriraj Hospital, Mahidol University NICHD CRS
Bangkok, 10700
Watcharee Lermankul, 66-2-4197000 Ext. 5695, Watcharee.ler@sipid.org
- Recruiting
31784, Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS
Chiang Mai, 50200
Daralak Tavornprasit, 66 5393 6148 ext. 176, daralak.t@cmu.ac.th
- Recruiting
5116 Chiangrai Prachanukroh Hospital NICHD CRS
Chiang Rai, 57000
Pra-ornsuda Sukrakanchana, 66-81-7468858, pra-ornsuda.sukrakanchana@phpt.org
- Recruiting
31802, Thai Red Cross AIDS Research Centre (TRC-ARC) CRS
Pathum Wan, 10330
Parawee Thongpaeng, 66-2-6523040 ext. 106, parawee.t@hivnat.org
Peru3 sites, 3 recruiting
- Recruiting
11301, Barranco CRS
Lima, 15063
Consuelo Tristan, +51 1-206-7800 ext. 210, ctristan@impactaperu.org
- Recruiting
31985, Socios En Salud Sucursal Perú CRS
Lima, 15234
Jimena Ruiz Cardenas, 51-933573391, gruiz_ses@pih.org
- Recruiting
11302, San Miguel CRS San Miguel
Lima
Diana M. Rojas Huasasquiche, 51-997502223, drojas@impactaperu.org
Brazil2 sites, 2 recruiting
- Recruiting
12201, Instituto de Pesquisas em AIDS do Rio Grande do Sul - IPARGS CRS
Porto Alegre, 91350
Rita Lira, +55 51-33572603, lrita@ghc.com.br
- Recruiting
12101, Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS
Rio de Janeiro, 21040
Brenda Hoagland, 55 21 38659122, brenda.hoagland@ini.fiocruz.br
Haiti2 sites, 2 recruiting
- Recruiting
30022, Les Centres GHESKIO Clinical Research Site (GHESKIO-INLR) CRS
Port-au-Prince, 6110
Jean Bernard Marc, 509-29426327, marcjeanbernard1@gmail.com
- Recruiting
31730, GHESKIO Institute of Infectious Diseases and Reproductive Health (GHESKIO - IMIS) CRS
Port-au-Prince, 6110
Yvetot Joseph, 509-36832867, yvetotjoseph@gheskio.org
Kenya2 sites, 2 recruiting
- Recruiting
12601, Moi University Clinical Research Center (MUCRC) CRS
Eldoret, 30100
Voila Kirui, 254-711-729856, viola.kirui@gmail.com
- Recruiting
12501, Kenya Medical Research Institute/Walter Reed Project Clinical Research Center (KEMRI/WRP) CRS
Kericho, 20200
Samwel Chirchir, +254 52-20 36100, samwel.chirchir@usamru-k.org
Malawi2 sites, 2 recruiting
- Not yet recruiting
30301, Blantyre CRS
Blantyre
Dumisile Huwa, 265-811885, dhuwa@jhp.mw
- Not yet recruiting
12001, Malawi CRS
Lilongwe, A-104
Thokozani Makuhunga, 265-175-5056, tmakuhunga@unclilongwe.org
Uganda2 sites, 2 recruiting
- Recruiting
12401, Joint Clinical Research Centre (JCRC)/Kampala CRS
Kampala, 10005
Sandra Rwambuya, 256-772-779283, dxr23@case.edu
- Recruiting
30293 MU-JHU Research Collaboration (MUJHU CARE LTD) CRS
Kampala, 23491
Deo Wabwire, 256-414-541044, dwabwire@mujhu.org
Botswana1 site, 1 recruiting
- Recruiting
12701, Gaborone CRS
Gaborone, 0000
Unoda Chakalisa, 267-393-0388, uchakalisa@bhp.org.bw
India1 site, 1 recruiting
- Recruiting
31441, Byramjee Jeejeebhoy Government Medical College (BJGMC) CRS
Pune, 411001
Nishi Suryavanshi, 91-9823248979, nsuryav1@jhmi.edu
Mexico1 site, 1 recruiting
- Not yet recruiting
32078, Nutrición-Mexico CRS
Mexico City, 14080
Alvaro Lopez Iñiguez, 52-5554870900 ext. 2420/2421, alvarolopez@revistamedicamd.com
Philippines1 site, 1 recruiting
- Recruiting
31981, TB HIV Innovations and Clinical Research Foundation Corp.
Cavite, 4118
Maria Gler, +63 917-823-0431, msgler@tbhivicr.org.ph
Vietnam1 site, 1 recruiting
- Recruiting
32483 National Lung Hospital CRS
Hanoi, 100000
Tran Viet Ha, 84-912-785886, vietha@live.unc.edu
Zimbabwe1 site, 1 recruiting
- Not yet recruiting
30313, Milton Park CRS
Harare, 30313
Patience Sibanda, 263-774-361-790, psibanda@uz-ctrc.org
About this study
Official title: A Phase 2 Randomized, Adaptive, Dose-Ranging, Open-Label Trial of Novel Regimens for the Treatment of Pulmonary Tuberculosis
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 study treatment (experimental or SOC, based on treatment arm assignment) followed by 18 weeks of SOC continuation phase treatment with 346 participants in Wave 1: 49-50 participants in each experimental treatment arm and 98-100 participants in the SOC treatment arm.
- Conditions
- Pulmonary Tuberculosis
- Being tested
- Isoniazid, Rifampicin, Pyrazinamide, Ethambutol, Bedaquiline
- Medical subject headings
- Tuberculosis, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IsoniazidDrug
Also called INH
INH 300 mg will be administered as one tablet orally once daily.
RifampicinDrug
Also called RIF
RIF 600 mg will be administered as two 300 mg capsules orally once daily on an empty stomach, 1 hour before or 2 hours after eating a meal.
PyrazinamideDrug
Also called PZA
PZA will be administered as 500 mg tablets, based on weight, orally once daily.
EthambutolDrug
Also called EMB
EMB will be administered as 400 mg tablets, based on weight, orally once daily.
BedaquilineDrug
Also called BDQ
BDQ 400 mg will be administered as four 100 mg tablets orally once daily with a meal for the first 2 weeks followed by 200 mg (two 100 mg tablets) orally once daily with a meal for 6 weeks.
PretomanidDrug
Also called Pa
Pa 200 mg will be administered as one 200 mg tablet orally once daily with a meal.
LinezolidDrug
Also called LZD
LZD 600 mg will be administered as one 600 mg tablet orally once daily.
TBI-223Drug
TBI-223 2400 mg once daily will be administered as four 600 mg tablets orally once daily with a meal.
SutezolidDrug
Also called SZD
SZD 1600 mg once daily will be administered as four 400 mg tablets orally once daily with a meal.
TBI-223Drug
TBI-223 1200 mg once daily will be administered as two 600 mg tablets orally with a meal.
SutezolidDrug
Also called SZD
SZD 800 mg once daily will be administered as two 400 mg tablets orally once daily with a meal.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Standard of Care (SOC) | Active comparator | * Weeks 1-8: INH 300 mg, RIF 600 mg, PZA weight-based, EMB weight-based
* Weeks 9-26: INH 300 mg, RIF 600 mg (or weight-based dosing following WHO guidance) Receives: Drug: Isoniazid; Drug: Rifampicin; Drug: Pyrazinamide; Drug: Ethambutol |
| Arm 2: Bedaquiline (BDQ), Pretomanid (Pa), and Linezolid (LZD) | Experimental | * Weeks 1-8: BDQ 400 mg for 2 weeks and then 200 mg for 6 weeks, Pa 200 mg, LZD 600 mg
* Weeks 9-26: INH 300 mg, RIF 600 mg (or weight-based dosing following WHO guidance) Receives: Drug: Isoniazid; Drug: Rifampicin; Drug: Bedaquiline; Drug: Pretomanid; Drug: Linezolid |
| Arm 3A: BDQ, Pa and TBI-223 (1200 mg) | Experimental | * Weeks 1-8: BDQ 400 mg for 2 weeks and then 200 mg for 6 weeks, Pa 200 mg, TBI-223 1200 mg
* Weeks 9-26: INH 300 mg, RIF 600 mg (or weight-based dosing following WHO guidance) Receives: Drug: Isoniazid; Drug: Rifampicin; Drug: Bedaquiline; Drug: Pretomanid; Drug: TBI-223 |
| Arm 3B: BDQ, Pa and TBI-223 (2400 mg) | Experimental | * Weeks 1-8: BDQ 400 mg for 2 weeks and then 200 mg for 6 weeks, Pa 200 mg, TBI-223 2400 mg
* Weeks 9-26: INH 300 mg, RIF 600 mg (or weight-based dosing following WHO guidance) Receives: Drug: Isoniazid; Drug: Rifampicin; Drug: Bedaquiline; Drug: Pretomanid; Drug: TBI-223 |
| Arm 4A: BDQ, Pa and Sutezolid (SZD) (800 mg) | Experimental | * Weeks 1-8: BDQ 400 mg for 2 weeks and then 200 mg for 6 weeks, Pa 200 mg, SZD 800 mg
* Weeks 9-26: INH 300 mg, RIF 600 mg (or weight-based dosing following WHO guidance) Receives: Drug: Isoniazid; Drug: Rifampicin; Drug: Bedaquiline; Drug: Pretomanid; Drug: Sutezolid |
| Arm 4B: BDQ, Pa and SZD (1600 mg) | Experimental | * Weeks 1-8: BDQ 400 mg for 2 weeks and then 200 mg for 6 weeks, Pa 200 mg, SZD 1600 mg
* Weeks 9-26: INH 300 mg, RIF 600 mg (or weight-based dosing following WHO guidance) Receives: Drug: Isoniazid; Drug: Rifampicin; Drug: Bedaquiline; Drug: Pretomanid; Drug: Sutezolid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in mean log10 (Time to positivity (TTP)) slope from longitudinal mycobacteria growth indicator tube (MGIT) liquid culture measurements over the first 6 weeks of treatment
for each experimental treatment arm compared to the SOC treatment arm.
Measured: Weeks 0, 1, 2, 3, 4 and 6
Difference in the cumulative proportion of participants having at least one new Grade 3 or higher adverse event (AE) by week 8 of treatment
for each experimental treatment arm compared to the SOC treatment arm.
Measured: 8 weeks
Secondary outcomes (8)
Cumulative proportion of participants with stable sputum culture conversion by week 8 as measured by culture-negative status via MGIT liquid culture at two consecutive measurements.
Measured: 8 weeks
Mean log10 TTP slope from longitudinal MGIT liquid culture measurements over the first 8 weeks of treatment.
Measured: Weeks 0, 1, 2, 3, 4, 6 and 8
Cumulative proportion of participants with a new Grade 3 or higher AE by week 26 of treatment.
Measured: 26 weeks
Cumulative proportion of participants with permanent discontinuation of study-provided anti-TB drugs due to any reason prior to Week 8 of treatment.
Measured: 8 weeks
Cumulative proportion of participants with permanent discontinuation or temporary discontinuation for ≥3 days of at least one anti-TB drug due to any reason prior to week 8 of treatment.
Measured: 8 weeks
Cumulative proportion of participants with permanent discontinuation of at least one anti-TB drug due to any reason prior to week 26 of treatment.
Measured: 26 weeks
A composite of stable culture conversion at week 6 of treatment and no new Grade 3 or higher AE through week 8.
Measured: 8 weeks
Proportion of participants with durable cure by 52 weeks after treatment initiation.
Measured: 52 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2024
- Study start11 Mar 2025
- Primary completion1 Mar 2027 (estimated)
- Study completion3 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Pulmonary TuberculosisStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 315 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- TB Alliance
- Responsible party
- Sponsor
- Investigators
- Radojka Savic, PharmD, PhD, Study chair, University of CaliforniaKelly Dooley, MD, PhD, Study chair, Vanderbilt University Medical CenterGustavo Velásquez, MD, MPH, Study chair, University of California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06192160
- Sponsor's protocol ID
- A5409
- Other IDs
- DOH-27-032024-5399
- Acronym
- RAD-TB
- Status last verified
- Oct 2026
- First submitted
- 20 Dec 2023
- Last updated
- 19 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie results in the publication, after deidentification.
Publications
Harrison LJ, Velasquez GE, Kempker RR, Imperial MZ, Nuermberger E, Dorman SE, Ignatius E, Granche J, Phillips PPJ, Furin J, Yang E, Foley C, Chiambah S, Rogers R, Van Grack A, Roa J, Shenje J, Nerette S, Kanyama C, Kyeyune RB, Mendoza-Ticona A, Murtaugh W, Foraida S, Goth M, Vernon A, Dooley KE, Savic RM. ACTG A5409 (RAD-TB): Study protocol for a phase 2 randomized, adaptive, dose-ranging, open-label trial of novel regimens for the treatment of pulmonary tuberculosis. Trials. 2025 Aug 15;26(1):291. doi: 10.1186/s13063-025-08973-w.
PubMed 40817073Harrison L, Velasquez GE, Kempker RR, Imperial MZ, Nuermberger E, Dorman SE, Ignatius E, Granche J, Phillips PP, Furin J, Yang E, Foley C, Chiambah S, Rogers R, Van Grack A, Roa J, Shenje J, Nerette S, Kanyama C, Kyeyune RB, Mendoza-Ticona A, Murtaugh W, Foraida S, Goth M, Vernon A, Dooley KE, Savic RM. ACTG A5409 (RAD-TB): Study Protocol for a Phase 2 Randomized, Adaptive, Dose-Ranging, Open-Label Trial of Novel Regimens for the Treatment of Pulmonary Tuberculosis. Res Sq [Preprint]. 2025 Mar 26:rs.3.rs-5931694. doi: 10.21203/rs.3.rs-5931694/v1.
PubMed 40195983