Efficacy and Tolerability of Bedaquiline, Delamanid, Levofloxacin, Linezolid, and Clofazimine to Treat MDR-TB

Prior treatment

• History of prior treatment with delamanid or linezolid for TB for greater than one month.
• Has at screening received ≥14 days of second-line anti-TB drugs during current TB episode
• At screening requires ongoing use of prohibited drugs indicated in section 4.2

Other illness

• History of allergy (hypersensitivity) or intolerability to one or more agents in the study regimen (i.e., Delamanid, Linezolid, Levofloxacin, Clofazimine or Bedaquiline)
• History of serotonin syndrome
• History of symptomatic ventricular arrhythmia or is taking anti-arrhythmic agents
• History of optic neuropathy or peripheral neuropathy
• History of Ehlers-Danlos Syndrome, Marfan Syndrome or aortic aneurism
• History of congestive heart failure

Lab values

• Has at screening laboratory results that meet one or more of the following criteria:
  • Hemoglobin concentration 8.0 g/dL (\<80 g/L)
  • Platelet count of \<80,000/mm3
  • Absolute neutrophil count (ANC) \<2000/ mm3
  • Serum creatinine \>2.0 mg/dL (\>177 µmol/L)
  • Serum ALT \>3x upper limit of normal (ULN)
  • Total bilirubin \>3x upper limit of normal (ULN)
  • Serum albumin \<2.8 g/dL (\<28 g/L)
  • For women of childbearing potential, a positive or indeterminate serum pregnancy test

Age

• In the investigator's judgement is unable to provide consent (if ≥18 years of age) or unable to provide assent (if \>12 years of age).

Other

• Current MTB isolate is known at screening to be fluoroquinolone-resistant.
• Has at screening a Karnofsky score of ≤40 or, in the opinion of the Investigator, is unlikely to survive 76 weeks.
• For women of childbearing potential, has a positive or indeterminate urine pregnancy test on the day of randomization.
• Has at screening a mean QTcF \>450 msec based on three ECGs.
• At screening, has weight less than 33 Kg

• Males and females age ≥12 years. Prior to study procedures, if ≥18 years of age, provides informed consent; if \<18 years of age, child provides informed assent and has a parent or guardian who provides informed consent on the participant's behalf.
• Has pulmonary TB based on investigator assessment of all available information (e.g., chest radiograph, sputum smear, culture, molecular testing).
• Has a sputum sample that is positive for M. tuberculosis that is rifamycin-resistant and fluoroquinolone-susceptible by molecular assay.
• Is HIV seropositive or seronegative; HIV serostatus must be assessed at screening if either (a) HIV serostatus is unknown, or (b) the last documented negative HIV test was more than two (2) months prior to screening.
• Willing to attend scheduled follow-up visits and undergo study assessments.
• Participants of child-bearing potential must agree either (a) to practice an adequate birth control (defined as one of the following oral contraceptives, intrauterine devices, contraceptive implants under the skin, contraceptive rings or patches or injections, diaphragms with spermicide or condoms with foam) or (b) to abstain from heterosexual intercourse during study regimen.