a phase iii study of oral sudapyridine (wx-081) tablets in rifampicin-resistant pulmonary tuberculosis patients

Conditions: Rifampin-Resistant Pulmonary Tuberculosis; Tuberculosis, Multidrug-Resistant (MDR-TB)

Summary: this is a multicenter, randomized, double-blind, active-controlled phase iii study to evaluate the efficacy and safety of sudapyridine (wx-081) combined with a background regimen (br) in patients with rifampicin-resistant pulmonary tuberculosis. approximately 450 participants will be screened over a period of up to 2 weeks and randomized in a 2:1 ratio to receive either sudapyridine or bedaquiline, in combination with placebo tablets and br, for 24 weeks. after the treatment period, participants will enter a background regimen period up to week 72, during which they will continue to receive br. a subset of participants will be included in the c-qt sub-study to assess intensive pk sampling and 12-lead ecg evaluations on day 1 pre-dose, day 14, and week 24. the study aims to provide robust data to support the use of sudapyridine as a treatment option for rifampicin-resistant pulmonary tuberculosis.

this phase iii clinical study is designed to evaluate the efficacy and safety of sudapyridine (wx-081) in combination with a background regimen (br) for the treatment of rifampicin-resistant pulmonary tuberculosis. the study will be conducted at multiple centers, employing a randomized, double-blind, active-controlled design. the study will consist of three phases: screening phase: duration: up to 2 weeks. approximately 450 participants with rifampicin-resistant pulmonary tuberculosis will be screened for eligibility. treatment phase: participants will be randomized in a 2:1 ratio into two groups: 1. sudapyridine group: sudapyridine (wx-081) with placebo and br. 2. bedaquiline group: bedaquiline with placebo and br. treatment duration: 24 weeks. background regimen phase: after completing the treatment phase, participants in both groups will continue to receive the background regimen (br) until week 72. the study aims to test the hypothesis that sudapyridine (wx-081), when combined with a background regimen, is effective and safe for treating rifampicin-resistant pulmonary tuberculosis. the data collected from this study will include primary and secondary endpoints related to efficacy and safety, pk/pd data, and cardiac safety evaluations. the sample size of approximately 450 participants is designed to provide adequate power to detect a statistically significant difference in outcomes between treatment groups. comprehensive data validation procedures and a robust statistical analysis plan will ensure the reliability and accuracy of the results.

Eligibility criteria:
inclusion criteria: * • body mass index (bmi) and body weight of subjects: 15.0≤bmi≤28.0 kg/m2, and 40kg≤ body weight ≤90kg; * for clinically diagnosed patients with tuberculosis whose drug sensitivity test has proved to be at least resistant to rifampicin, phenotypic or molecular drug sensitivity test results within 3 months before the subject signs informed consent can be accepted; * direct sputum smear positive for acid-fast bacilli (afb at least 1+); * willing to discontinue all previous anti-tuberculosis drugs and accept a 7-day washout period; * non-lactating and pregnant women who agree to use contraception throughout the treatment; or the male patient's spouse agrees to use contraception throughout the treatment. exclusion criteria: * • allergic to any study drug or its ingredients; * a history of alcohol dependence or drug abuse; * with hematogenous disseminated pulmonary tuberculosis or extrapulmonary tuberculosis; * drug susceptibility test before screening showed resistance to more than 4 of the 8 antituberculosis drugs in this study; * have taken bedaquiline before; * hiv-positive patients; * laboratory obvious abnormalities; * a history of pointy torsion ventricular tachycardia or cardiac risk factors for pointy torsion ventricular tachycardia; * repeated qtcf intervals \> 450ms; clinically significant ventricular arrhythmias that may require medical or surgical treatment; * documented cardiovascular diseases; * peripheral neuropathy ctcae grade 3 or grade 4; grade 1 or grade 2 neuropathy that the investigator believes is likely to progress/worsen over the course of the study; optic neuritis; * any serious cardiovascular, kidney, liver, blood, tumor, endocrine and metabolic, autoimmune or rheumatic diseases.

Keywords: rifampin-resistant tuberculosis multidrug-resistant tuberculosis (mdr-tb) pulmonary tuberculosis sudapyridine (wx-081) bedaquiline antitubercular agents randomized controlled trial background regimen therapy