Trial of Novel Regimens for the Treatment of Pulmonary Tuberculosis
NCT ID: NCT06192160
Last Updated: 2025-11-12
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2
315 participants
INTERVENTIONAL
2025-03-11
2027-08-11
Brief Summary
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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.
Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Arm 3A: BDQ, Pa and TBI-223 (1200 mg)
* 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
Isoniazid
INH 300 mg will be administered as one tablet orally once daily.
Rifampicin
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.
Bedaquiline
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.
Pretomanid
Pa 200 mg will be administered as one 200 mg tablet orally once daily with a meal.
TBI-223
TBI-223 1200 mg once daily will be administered as two 600 mg tablets orally with a meal.
Arm 3B: BDQ, Pa and TBI-223 (2400 mg)
* 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
Isoniazid
INH 300 mg will be administered as one tablet orally once daily.
Rifampicin
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.
Bedaquiline
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.
Pretomanid
Pa 200 mg will be administered as one 200 mg tablet orally once daily with a meal.
TBI-223
TBI-223 2400 mg once daily will be administered as four 600 mg tablets orally once daily with a meal.
Arm 4A: BDQ, Pa and Sutezolid (SZD) (800 mg)
* 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
Isoniazid
INH 300 mg will be administered as one tablet orally once daily.
Rifampicin
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.
Bedaquiline
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.
Pretomanid
Pa 200 mg will be administered as one 200 mg tablet orally once daily with a meal.
Sutezolid
SZD 800 mg once daily will be administered as two 400 mg tablets orally once daily with a meal.
Arm 4B: BDQ, Pa and SZD (1600 mg)
* 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
Isoniazid
INH 300 mg will be administered as one tablet orally once daily.
Rifampicin
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.
Bedaquiline
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.
Pretomanid
Pa 200 mg will be administered as one 200 mg tablet orally once daily with a meal.
Sutezolid
SZD 1600 mg once daily will be administered as four 400 mg tablets orally once daily with a meal.
Arm 1: Standard of Care (SOC)
* Weeks 1-8: INH 300 mg, RIF 600 mg, PZA weight-based, EMB weight-based
* Weeks 9-26: INH 300 mg, RIF 600 mg
Isoniazid
INH 300 mg will be administered as one tablet orally once daily.
Rifampicin
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.
Pyrazinamide
PZA will be administered as 500 mg tablets, based on weight, orally once daily.
Ethambutol
EMB will be administered as 400 mg tablets, based on weight, orally once daily.
Arm 2: Bedaquiline (BDQ), Pretomanid (Pa), and Linezolid (LZD)
* 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
Isoniazid
INH 300 mg will be administered as one tablet orally once daily.
Rifampicin
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.
Bedaquiline
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.
Pretomanid
Pa 200 mg will be administered as one 200 mg tablet orally once daily with a meal.
Linezolid
LZD 600 mg will be administered as one 600 mg tablet orally once daily.
Interventions
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Isoniazid
INH 300 mg will be administered as one tablet orally once daily.
Rifampicin
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.
Pyrazinamide
PZA will be administered as 500 mg tablets, based on weight, orally once daily.
Ethambutol
EMB will be administered as 400 mg tablets, based on weight, orally once daily.
Bedaquiline
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.
Pretomanid
Pa 200 mg will be administered as one 200 mg tablet orally once daily with a meal.
Linezolid
LZD 600 mg will be administered as one 600 mg tablet orally once daily.
TBI-223
TBI-223 2400 mg once daily will be administered as four 600 mg tablets orally once daily with a meal.
Sutezolid
SZD 1600 mg once daily will be administered as four 400 mg tablets orally once daily with a meal.
TBI-223
TBI-223 1200 mg once daily will be administered as two 600 mg tablets orally with a meal.
Sutezolid
SZD 800 mg once daily will be administered as two 400 mg tablets orally once daily with a meal.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
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
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.
18 Years
ALL
No
Sponsors
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TB Alliance
UNKNOWN
National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Responsible Party
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Principal Investigators
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Radojka Savic, PharmD, PhD
Role: STUDY_CHAIR
University of California
Kelly Dooley, MD, PhD
Role: STUDY_CHAIR
Vanderbilt University Medical Center
Gustavo Velásquez, MD, MPH
Role: STUDY_CHAIR
University of California
Locations
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12701, Gaborone CRS
Gaborone, , Botswana
12201, Hospital Nossa Senhora da Conceicao CRS
Porto Alegre, , Brazil
12101, Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS
Rio de Janeiro, , Brazil
30022, Les Centres GHESKIO Clinical Research Site (GHESKIO-INLR) CRS
Port-au-Prince, , Haiti
31730, GHESKIO Institute of Infectious Diseases and Reproductive Health (GHESKIO - IMIS) CRS
Port-au-Prince, , Haiti
31441, Byramjee Jeejeebhoy Medical College (BJMC) CRS
Pune, , India
12601, Moi University Clinical Research Center (MUCRC) CRS
Eldoret, , Kenya
12501, Kenya Medical Research Institute/Walter Reed Project Clinical Research Center (KEMRI/WRP) CRS
Kericho, , Kenya
30301, Blantyre CRS
Blantyre, , Malawi
12001, Malawi CRS
Lilongwe, , Malawi
32078, Nutrición-Mexico CRS
Mexico City, , Mexico
11301, Barranco CRS
Lima, , Peru
31985, Socios En Salud Sucursal Perú CRS
Lima, , Peru
31981, TB HIV Innovations and Clinical Research Foundation Corp.
Cavite, , Philippines
31793, South African Tuberculosis Vaccine Initiative (SATVI) CRS
Cape Town, , South Africa
31792, University of Cape Town Lung Institute (UCTLI) CRS
Cape Town, , South Africa
31422, CAPRISA eThekwini CRS
Durban, , South Africa
11201, Durban International CRS
Durban, , South Africa
12301, Soweto ACTG CRS
Johannesburg, , South Africa
11101, University of the Witwatersrand Helen Joseph (WITS HJH) CRS
Johannesburg, , South Africa
31684, Rustenburg CRS
Rustenburg, , South Africa
31784, Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS
Chiang Mai, , Thailand
5116 Chiangrai Prachanukroh Hospital NICHD CRS
Chiang Rai, , Thailand
31802, Thai Red Cross AIDS Research Centre (TRC-ARC) CRS
Pathum Wan, , Thailand
12401, Joint Clinical Research Centre (JCRC)/Kampala CRS
Kampala, , Uganda
32483 National Lung Hospital CRS
Hanoi, , Vietnam
30313, Milton Park CRS
Harare, , Zimbabwe
Countries
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Central Contacts
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Facility Contacts
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Unoda Chakalisa
Role: primary
Rita Lira
Role: primary
Brenda Hoagland
Role: primary
Samuel Pierre
Role: primary
Yvetot Joseph
Role: primary
Nishi Suryavanshi
Role: primary
Voila Kirui
Role: primary
Samwel Chirchir
Role: primary
Dumisile Huwa
Role: primary
Thokozani Makuhunga
Role: primary
Brenda Crabtree
Role: primary
Consuelo Tristan
Role: primary
Bruno Martel Chavez
Role: primary
Maria Gler
Role: primary
Lynnett Stone
Role: primary
Tammy Krige
Role: primary
Nivashnee Naicker
Role: primary
Rosie Mngqibisa
Role: primary
Suri Moonsamy
Role: primary
Betty Matome
Role: primary
Tiro Dinake
Role: primary
Daralak Tavornprasit
Role: primary
Pra-ornsuda Sukrakanchana
Role: primary
Parawee Thongpaeng
Role: primary
Sandra Rwambuya
Role: primary
Tran Viet Ha
Role: primary
Patience Sibanda
Role: primary
References
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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.
Harrison 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.
Other Identifiers
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DOH-27-032024-5399
Identifier Type: OTHER
Identifier Source: secondary_id
A5409
Identifier Type: -
Identifier Source: org_study_id