Drug Susceptible Pulmonary Tuberculosis
Conditions
Keywords
TBD09, oxazolidinone, bedaquiline, pretomanid, linezolid, drug-susceptible pulmonary tuberculosis
Brief summary
The purpose of this study is to evaluate if TBD09 in combination with other active agents in adults with drug sensitive pulmonary tuberculosis has potential to be safe and effective.
Interventions
DRUGBedaquiline, pretomanid and TBD09
Group 1 (30 participants): The combination of TBD09 (100 mg three times weekly, TIW), bedaquiline (200 mg daily, QD), and pretomanid (200 mg QD), 28 days
DRUGBedaquiline, pretomanid and linezolid
Group 5 (30 participants): The combination of linezolid (600 mg QD), bedaquiline (200 mg QD), and pretomanid (200 mg QD), 28 days
Sponsors
Gates Medical Research Institute
IQVIA RDS Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-65 years at consent * Body weight 35-100 kg at screening * Written informed consent obtained * Newly diagnosed rifampicin-sensitive pulmonary TB * Molecular confirmation of M. tuberculosis on Xpert MTB/RIF Ultra * ≥1+ AFB smear or Xpert Ultra low, medium, or high semi-quantitative result * Rifampicin sensitivity on molecular test * Chest X-ray consistent with TB (Investigator assessment) * Able to spontaneously produce sputum * Reproductive requirements met * Women of childbearing potential: 2 approved contraceptive methods or abstinence * Males: contraception or abstinence through 90 days post-dose
Exclusion criteria
* Prior anti-TB treatment for the current TB episode within 60 days * Prior medication active against Mtb within 3 months * Evidence of extra-thoracic TB, per investigator judgement * Prior treatment completion for TB within 3 years * 2 or more prior episodes of TB * Clinically significant history of or current medical condition posing safety risk * If HIV positive: * Not on ARVs or taking ARVs for \<3 months prior to screening OR * CD4+ count \<200cells/uL at screening OR * HIV viral load \>200 copies /mL at screening OR * AIDS infection or malignancies * Meets any of the following laboratory values during screening: * AST, ALT, or ALP ≥2.5× ULN * Total bilirubin ≥1.2× ULN * eGFR \<60 mL/min/1.73 m² * Hemoglobin \<9.0 g/dL (male) or \<8.5 g/dL (female) * White blood cell count \<2,000/mm³ * Absolute neutrophil count \<800/mm³ * Platelet count ≤100,000/mm³ * Positive hepatitis B surface antigen * Positive hepatitis C antibody * HbA1c ≥8.0% * Current or recent systemic immunosuppressive therapy, including corticosteroids * Significant drug or alcohol abuse affecting compliance or safety * Pregnant or breastfeeding, positive pregnancy test, or planning pregnancy shortly after treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bactericidal Activity | From randomization through Day 28 (EOT) | Average daily change in MGIT sputum culture TTD from baseline to end-of-treatment (EOT) |
| Safety: SAEs | Screening through Day 35 (EOS) | Proportion of participants with this event |
| Safety: TEAEs | Screening through Day 35 (EOS) | Proportion of participants with this event |
| Safety: AESIs | Screening through Day 35 (EOS) | Proportion of participants with this event |
| Safety: AEs leading to treatment discontinuation | Screening through Day 35 (EOS) | Proportion of participants with this event |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety: Hematologic Effect | Randomization through Day 35 (EOS) | Proportion of participants who meet each of the following binary classifications of platelets, absolute neutrophil count (ANC), total white blood cell count (WBC), absolute lymphocyte count (ALC), and hemoglobin: 1. Post-baseline result \< lower limit of normal (LLN) among participants with baseline result \> LLN (yes/no) 2. Post-baseline result \< 50% of LLN (yes/no) 3. Post-baseline result ≥50% decrease relative to baseline (yes/no) |
| Safety: Visual Acuity Assessment | Randomization through Day 35 (EOS) | Proportion of participants with worsening of postbaseline visual acuity score of 2 lines or more in either eye using Snellen-type charts |
| Safety: Colour Vision Assessment | Randomization through Day 35 (EOS) | Proportion of participants with a new or worsening post-baseline color vision abnormality in either eye (by severity grade) using Ishihara plates |
| Safety: Brief Peripheral Neuropathy Screen (BPNS) score | Randomization through Day 35 (EOS) | Proportion of participants with a reported new or worsening post-baseline peripheral neuropathy symptom on BPNS in either lower extremity (overall and by severity grade) |
| Bactericidal activity | Day 28 (EOT) | Proportion of participants with negative MGIT sputum cultures at D28 |
| Maximum plasma concentration (Cmax) of TBD09 | Day 1 and Day 28 | Concentrations of TBD09 administered in an investigational combination regimen. |
| Time to maximum plasma concentration (Tmax) of TBD09 | Day 1 and Day 28 | Concentrations of TBD09 administered in an investigational combination regimen. |
| Area under the curve from 0 to 24 hours (AUC0-24) of plasma concentration of TBD09 | Day 1 | Concentrations of TBD09 administered in an investigational combination regimen. |
| Area under the curve from 0 to infinity (AUC0-inf) of plasma concentration of TBD09 | Day 28 | Concentrations of TBD09 administered in an investigational combination regimen. |
| Area under the curve over the dosing interval on day 28 (AUCtau) of plasma concentration of TBD09 | Day 28 | Concentrations of TBD09 administered in an investigational combination regimen. |
| Accumulation ratio (Area under the curve from 0 to the end of the dosing interval (AUCtau) / AUC0-24), Day 28 vs Day 1 of plasma concentration of TBD09 | Day 1 and Day 28 | Concentrations of TBD09 administered in an investigational combination regimen. |
Countries
South Africa
Contacts
CONTACTGates MRI
STUDY_DIRECTORGates MRI
Gates Medical Research Institute
Outcome results
None listed