Sudapyridine (WX-081) in RR-TB Patients

Study Overview
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Brief Summary
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The objective of this study is to demonstrate that the antibacterial activity of Sudapyridine (WX-081) is not inferior to Bedaquiline when added to a Background Regimen (BR) for treatment of rifampicin- resistant TB. Also, safety and clinical outcome will be evaluated.

Detailed Description
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This is a multicenter, randomized, double-blind, positive-controlled Phase III study to evaluate the efficacy and safety of Sudapyridine (WX-081) in combination with background medication (BR) in patients with rifampicin-resistant tuberculosis.

Official Title
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A Multicenter, Randomized, Double-blind, Positive Control Study to Evaluate the Efficacy and Safety of Sudapyridine (WX-081) Tables in Patients With Rifampicin-resistant Pulmonary Tuberculosis

Conditions
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Rifampicin-resistant Tuberculosis

Intervention / Treatment
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* Drug: Sudapyridine
* Drug: Bedaquiline


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sudapyridine arm<br> | Drug: Sudapyridine<br>* Two weeks of loading dose followed by twenty-two weeks of maintenance dose Drug: Background regimen (BR) for RR-TB Background regimen (BR) for RR-TB selected according to WHO and local guidelines for up to 72 weeks.<br>|
| Active Comparator: Bedaquiline arm<br> | Drug: Bedaquiline<br>* Two weeks of loading dose followed by twenty-two weeks of maintenance dose Drug: Background regimen (BR) for RR-TB Background regimen (BR) for RR-TB selected according to WHO and local guidelines for up to 72 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of participants with Sputum Culture Conversion | Sputum culture conversion is defined as having two consecutive negative cultures at least 28 days apart, not followed by a confirmed positive culture during the considered time period | Time frame: week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Time to Sputum Culture Conversion | Sputum culture conversion is defined as having two consecutive negative cultures at least 28 days apart, not followed by a confirmed positive culture during the considered time period | Time Frame: Week 24 | 
| The percentage of participants with Sputum Culture Conversion and treatment success | The clinical effectiveness of this study was evaluated based on treatment success, which included both treatment completion and the achievement of favorable outcomes. | Time Frame: Week 72 |