A Phase III Study of Oral Sudapyridine (WX-081) Tablets in Rifampicin-Resistant Pulmonary Tuberculosis Patients

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.