Prospective, Randomized, Partially Blinded, Phase 2 Study of the Efficacy and Tolerability of Bedaquiline, Delamanid, Levofloxacin, Linezolid, and Clofazimine for Treatment of Patients With MDR-TB

H39017

Multidrug-resistant tuberculosis (MDR-TB) is tuberculosis (TB) that is resistant to at least isoniazid and rifampicin, the two most important anti-TB drugs. It occurs in 3.6% of newly diagnosed TB patients in the world and 17% of patients who have been previously treated. In 2017, approximately 600,000 people were estimated to have acquired MDR-TB. However, only 25% of persons with MDR-TB were diagnosed and started on treatment, reflecting inadequate diagnostic capacity and lack of TB treatment capacity. In this multicenter, randomized, partially blinded, four-arm, phase 2 study, the investigators will examine the efficacy and safety of an all-oral regimen of bedaquiline, delamanid, levofloxacin, linezolid, and clofazimine given for 16, 24, 32 or 40 weeks

2022-06-07

2027-05-01

2027-05-01

Recruiting

Early phase I

220

Inclusion Criteria: 1. 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. 2. Has pulmonary TB based on investigator assessment of all available information (e.g., chest radiograph, sputum smear, culture, molecular testing). 3. Has a sputum sample that is positive for M. tuberculosis that is rifamycin-resistant and fluoroquinolone-susceptible by molecular assay. 4. 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. 5. Willing to attend scheduled follow-up visits and undergo study assessments. 6. 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. Exclusion Criteria: 1. Current MTB isolate is known at screening to be fluoroquinolone-resistant. 2. History of allergy (hypersensitivity) or intolerability to one or more agents in the investigational regimens (i.e., Arms 1 and 2) 3. History of serotonin syndrome 4. History of symptomatic ventricular arrhythmia or is taking anti-arrhythmic agents 5. History of optic neuropathy or peripheral neuropathy 6. History of Ehlers-Danlos Syndrome, Marfan Syndrome or aortic aneurism 7. History of prior treatment with delamanid or linezolid for TB for greater than one month. 8. Has at screening received ≥14 days of second-line anti-TB drugs during current TB episode 9. Has at screening a Karnofsky score of ≤40 or, in the opinion of the Investigator, is unlikely to survive 76 weeks. 10. 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 11. For women of childbearing potential, has a positive or indeterminate urine pregnancy test on the day of randomization. 12. Has at screening a mean QTcF \>450 msec based on three ECGs. 13. At screening requires ongoing use of prohibited drugs indicated in section 4.2 14. At screening, has weight less than 33 Kg 15. 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). 16. History of congestive heart failure

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 220, 'type': 'ESTIMATED'}}

2024-04-12