A Pan-TB Regimen Targeting Host and Microbe

Prior treatment

• Having participated in other clinical trials with investigational agents within 8 weeks prior to trial start or currently enrolled in an investigational trial.
• Prior TB treatment in the preceding 6 months
• Angina pectoris requiring treatment with nitroglycerin or other nitrates
• History of unstable Diabetes Mellitus requiring hospitalization for hyper- or hypo-glycaemia within the past year prior to start of screening.
• Use of systemic corticosteroids within the past 28 days.
• Patients requiring treatment with medications not compatible with rifampin, such as HIV-1 protease inhibitors
• Patients requiring treatment with antidepressants, including MAO inhibitors and SSRIs.

Other illness

• Any condition for which participation in the trial, as judged by the investigator, could compromise the well-being of the subject or prevent, limit or confound protocol specified assessments
• TB meningitis or spondylitis, or other forms of severe tuberculosis with high risk of a poor outcome as judged by the investigator.
• History of allergy or hypersensitivity to any of the trial therapies or related substances.
• Cardiac arrhythmia requiring medication, or any clinically significant ECG abnormality, in the opinion of the investigator

Lab values

• Subjects with any of the following abnormal laboratory values:
  • HBsAg positive
  • creatinine \>2 mg/dL
  • hemoglobin \<8 g/dL
  • platelets \<100x109 cells/L
  • serum potassium \<3.5 mM/L
  • alanine aminotransferase (ALT) ≥2.0 x ULN
  • alkaline phosphatase (AP) \>5.0 x ULN
  • total bilirubin \>1.5 mg/dL
  • random blood glucose \>200 mg/dL

Other

• Current or imminent (within 24 hr) treatment for malaria.
• Pregnant or nursing
• Is critically ill, and in the judgment of the investigator has a diagnosis likely to result in death during the trial or the follow-up period.

• Aged 18 to 65 years
• Willing and able to provide signed written consent prior to undertaking any trial-related procedures, or, in the case of illiteracy, witnessed oral consent
• Body weight (in light clothing without shoes) between 30 and 90 kg.
• Radiographic evidence of pulmonary tuberculosis
• Positive Xpert TB/RIF (original or Ultra) for MTB
• RIF susceptibility diagnosed by Xpert TB/RIF, with subsequent culture confirmation
• If sexually active, willing to use an effective contraceptive method for the duration of tuberculosis treatment
• HIV-1 seronegative, or if HIV-1 seropositive, CD4 T cell count ≥100/µl and either receiving ART or willing to start ART during study participation
• SARS-CoV-2 PCR or antigen test negative, or if positive, either fully vaccinated against Covid-19 or with D-dimer \<0.8 ug/ml
• Willing to adhere to a diet excluding tyramine-rich foods (certain mold-ripened cheeses and cured meats), and to avoid eating grapefruits and pomelos