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NCT06192160 | RECRUITING | Pulmonary Tuberculosis

Trial of Novel Regimens for the Treatment of Pulmonary Tuberculosis
Sponsor:

National Institute of Allergy and Infectious Diseases (NIAID)

Brief 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.

Condition or disease

Pulmonary Tuberculosis

Intervention/treatment

Isoniazid

Rifampicin

Pyrazinamide

Ethambutol

Bedaquiline

Pretomanid

Linezolid

TBI-223

Sutezolid

TBI-223

Sutezolid

Phase

PHASE2

Study Type : INTERVENTIONAL
Estimated Enrollment : 315 participants
Masking : NONE
Primary Purpose : TREATMENT
Official Title : A Phase 2 Randomized, Adaptive, Dose-Ranging, Open-Label Trial of Novel Regimens for the Treatment of Pulmonary Tuberculosis
Actual Study Start Date : 2025-03-11
Estimated Primary Completion Date : 2026-03-11
Estimated Study Completion Date : 2027-03-11

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: 18 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers:
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.
Trial of Novel Regimens for the Treatment of Pulmonary Tuberculosis

Location Details

NCT06192160

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How to Participate

Want to participate in this study, select a site at your convenience, send yourself email to get contact details and prescreening steps.

Locations

NOT YET RECRUITING

Botswana,

12701, Gaborone CRS

Gaborone, Botswana, 0000

NOT YET RECRUITING

Brazil,

12201, Hospital Nossa Senhora da Conceicao CRS

Porto Alegre, Brazil, 91350

RECRUITING

Brazil,

12101, Evandro Chagas Clinical Research Institute (IPEC) CRS

Rio de Janeiro, Brazil, 21040

NOT YET RECRUITING

Haiti,

30022, Les Centers GHESKIO Clinical Research Site (GHESKIO-INLR) CRS

Port-au-Prince, Haiti, 6110

NOT YET RECRUITING

Haiti,

31730, GHESKIO Institute of Infectious Diseases and Reproductive Health (GHESKIO - IMIS) CRS

Port-au-Prince, Haiti, 6110

NOT YET RECRUITING

India,

31441, Byramjee Jeejeebhoy Medical College (BJMC) CRS

Pune, India, 411001

NOT YET RECRUITING

Kenya,

12601, Moi University Clinical Research Center (MUCRC) CRS

Eldore, Kenya, 30100

RECRUITING

Kenya,

12501, Kenya Medical Research Institute/Walter Reed Project Clinical Research Center (KEMRI/WRP) CRS

Kericho, Kenya, 20200

NOT YET RECRUITING

Malawi,

30301, Blantyre CRS

Blantyre, Malawi, 265

NOT YET RECRUITING

Malawi,

12001, Malawi CRS

Lilongwe, Malawi, A-104

NOT YET RECRUITING

Mexico,

32078, Nutrition-Mexico CRS

Mexico City, Mexico, 14080

NOT YET RECRUITING

Peru,

11301, Barranco CRS

Lima, Peru, 1010

NOT YET RECRUITING

Peru,

31985, Health Partners Peru Branch CRS

Lima, Peru, 15046

NOT YET RECRUITING

Philippines,

31981, TB HIV Innovations and Clinical Research Foundation Corp.

Cavite, Philippines, 4114

RECRUITING

South Africa,

31793, South African Tuberculosis Vaccine Initiative (SATVI) CRS

Cape Town, South Africa, 6850

NOT YET RECRUITING

South Africa,

31792, University of Cape Town Lung Institute (UCTLI) CRS

Cape Town, South Africa, 7700

NOT YET RECRUITING

South Africa,

31422, CAPRISA Durban CRS

Durban, South Africa, 40001

NOT YET RECRUITING

South Africa,

11201, Durban International CRS

Durban, South Africa, 4091

NOT YET RECRUITING

South Africa,

12301, Soweto ACTG CRS

Johannesburg, South Africa, 1864

NOT YET RECRUITING

South Africa,

11101, University of the Witwatersrand Helen Joseph (WITS HJH) CRS

Johannesburg, South Africa, 2193

RECRUITING

South Africa,

31684, Rustenburg CRS

Rustenburg, South Africa,

NOT YET RECRUITING

Thailand,

31784, Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS

Chiang Mai, Thailand, 50200

NOT YET RECRUITING

Thailand,

5116 Chiangrai Prachanukroh Hospital NICHD CRS

Chiang Rai, Thailand, 57000

NOT YET RECRUITING

Thailand,

31802, Thai Red Cross AIDS Research Centre (TRC-ARC) CRS

Pathum Wan, Thailand, 10330

NOT YET RECRUITING

Uganda,

12401, Joint Clinical Research Centre (JCRC)/Kampala CRS

Kampala, Uganda, 10005

NOT YET RECRUITING

Vietnam,

32483 National Lung Hospital CRS

Hanoi, Vietnam, 100000

NOT YET RECRUITING

Zimbabwe,

30313, Milton Park CRS

Harare, Zimbabwe, 30313