A Multicenter, Randomized, Double-Blind, Active-Controlled Phase III Clinical Study to Evaluate the Efficacy and Safety of Oral Sudapyridine (WX-081) Tablets in Patients With Rifampicin-Resistant Pulmonary Tuberculosis
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 450
- 试验地点
- 2
- 主要终点
- Sputum Culture Conversion Rate at Week 24
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Participants, care providers, investigators, and outcome assessors will be blinded to the intervention assignments to ensure unbiased assessment.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •• 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.
排除标准
- •• 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.
研究组 & 干预措施
Sudapyridine (WX-081) Group
Participants in this group will receive Sudapyridine (WX-081) combined with background regimen (BR). Treatment starts with a loading dose of Sudapyridine for 2 weeks (450 mg once daily for 7 days, followed by 300 mg once daily for 7 days). This is followed by a maintenance dose of 150 mg once daily from Week 3 to Week 24. During the 24-week treatment period, participants will also receive a placebo for bedaquiline and continue their background regimen (BR). After the 24-week treatment period, participants will enter the background regimen phase and continue BR until Week 72.
干预措施: Sudapyridine (Drug)
Bedaquiline Group
Participants in this group will receive Bedaquiline combined with background regimen (BR). Treatment starts with a loading dose of Bedaquiline for 2 weeks (400 mg once daily), followed by a maintenance dose of 200 mg three times per week (with at least 48 hours between doses) from Week 3 to Week 24. During the 24-week treatment period, participants will also receive a placebo for Sudapyridine and continue their background regimen (BR). After the 24-week treatment period, participants will enter the background regimen phase and continue BR until Week 72.
干预措施: Bedaquiline (Drug)
结局指标
主要结局
Sputum Culture Conversion Rate at Week 24
时间窗: Week 24
Proportion of participants achieving sputum culture conversion (SCC) at Week 24 of treatment, measured as a percentage.
次要结局
- Time to Sputum Culture Conversion(Up to Week 72)
- Treatment Success Rate at Week 72(Week 72)
- Sputum Culture Conversion Rates at Multiple Time Points(Up to Week 72)