A multi-centre, randomized, open-label clinical trial. All treatments will be administered orally (PO) on days 1-14.
15 participants will be recruited into each treatment arm in two sequential cohorts. Each cohort will have participants enrolled onto the experimental regimen(s) or the standard of care (SOC; HRZE) control arm.
• Cohort 1 aims to generate safety data for a higher dose of alpibectir plus ethionamide 125 mg and 250 mg (arm 1: A45E125 and arm2: A45E250).
Once 5 participants have enrolled into arms 1 and 2 each, and completed 14 days of treatment, an interim safety review will be conducted to determine whether the study can advance to cohort 2.
• Cohort 2 will investigate safety of alpibectir and ethionamide (A45E250) in combination with rifampicin, pyrazinamide and ethambutol (A45E250RZE).
Participants on HRZE will serve as control for the EBA quantitative mycobacteriology in each cohort, and additionally as a safety benchmark for the A45E250RZE arm. The study is not statistically powered to make between arm comparisons of activity or safety. The treatment will not be blinded but the mycobacteriology laboratory staff performing the endpoint assays will remain blinded until analysis of the EBA results.
Provide written, informed consent prior to all trial-related procedures and willing to adhere to all required study procedures and restrictions for the duration of the trial.
Male or female, aged between 18 and 65 years, inclusive.
Body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive.
Newly diagnosed and untreated for this episode of pulmonary TB.
Evidence of clinically significant conditions or findings, other than TB, that might compromise safety or the interpretation of trial endpoints, per discretion of the investigator.
Poor general condition where any delay in treatment cannot be tolerated per discretion of the investigator.
History of epilepsy, seizures or other neuropsychiatric disorders that might compromise safety or the interpretation of trial endpoints, per discretion of the investigator.
Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, persistent jaundice (with the exception of Gilbert's syndrome or asymptomatic gallstones).
TASK Applied Science
Lead sponsor
Innovative Medicines Initiative
Collaborator