Tuberculosis
Conditions
Interventions
bedaquiline
linezolid
TBI223 1200mg
TBI223 2400 mg
sutezolid SZD 800 mg
sutezolid SZD 1600 mg
Sponsors
National Institute of Allergy and Infectious Diseases
Eligibility
Sex/Gender
All
Inclusion 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 [Hanrahan 2014]. 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, 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. 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 externalquality assurance programs: 8.For individuals assigned female sex at birth and who are of reproductive potential, negative pregnancy test (urine HCG or serum ß-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. 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.
Exclusion criteria
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 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. 14.5 Known allergy/sensitivity or any hypersensitivity to components of investigational agents or their formulation. 15.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. 16.Taking an investigational drug or vaccine within 30 days prior to study entry.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1.Efficacy: TTP from longitudinal MGIT liquid culture measurements at weeks 0, 1, 2, 3, 4, and 6 of treatment. Estimand: Difference in mean (experimental arm versus SOC) log10 (TTP) slope from longitudinal MGIT liquid culture measurements over the first 6 weeks of treatment. 2. Safety: New Grade 3 or higher adverse event through week 8 of treatment. Estimand: Difference in cumulative proportion (experimental arm versus SOC) of having at least one new Grade 3 or higher adverse event by week 8 of treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1.Stable sputum culture conversion by week 8 as measured by culture negative status via MGIT liquid culture at two consecutive measurements. 2.TTP slope from longitudinal MGIT liquid culture measurements over the first 8 weeks of treatment. 3. New Grade 3 or higher AE through week 26 of treatment. 4 Permanent discontinuation of study-provided anti-TB drugs due to any reason prior to week 8 of treatment. 5 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. 6 Permanent discontinuation of at least one anti-TB drug due to any reason prior to week 26 of treatment. 7 A composite of stable culture conversion at week 6 of treatment and no new Grade 3 or higher adverse event through week 8. 8 Durable cure by 52 weeks after treatment initiation. | — |
Countries
Kenya
Contacts
Public ContactJhoanna Roa
ACTG Network Coordinating Center DLH
Outcome results
None listed