Rifampin-Resistant Pulmonary Tuberculosis, Tuberculosis, Multidrug-Resistant (MDR-TB)
Conditions
Keywords
Rifampin-Resistant Tuberculosis, Multidrug-Resistant Tuberculosis (MDR-TB), Pulmonary Tuberculosis, Sudapyridine (WX-081), Bedaquiline, Antitubercular Agents, Randomized Controlled Trial, Background Regimen Therapy
Brief 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.
Detailed description
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.
Interventions
DRUGSudapyridine
Sudapyridine (WX-081) will be administered as a loading dose for 2 weeks (450 mg once daily for 7 days, followed by 300 mg once daily for 7 days) and a maintenance dose (150 mg once daily) from Week 3 to Week 24. The intervention is combined with background regimen (BR) and placebo for bedaquiline.
DRUGBedaquiline
Bedaquiline will be administered as a loading dose for 2 weeks (400 mg once daily) and a maintenance dose (200 mg three times per week, with at least 48 hours between doses) from Week 3 to Week 24. The intervention is combined with background regimen (BR) and placebo for Sudapyridine.
Sponsors
Shanghai Jiatan Pharmatech Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Participants, care providers, investigators, and outcome assessors will be blinded to the intervention assignments to ensure unbiased assessment.
Intervention model description
Participants are randomized into two groups (Sudapyridine and Bedaquiline) for parallel treatment evaluation.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sputum Culture Conversion Rate at Week 24 | Week 24 | Proportion of participants achieving sputum culture conversion (SCC) at Week 24 of treatment, measured as a percentage. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Sputum Culture Conversion | Up to Week 72 | Time required for participants to achieve sputum culture conversion (SCC) during the study period. |
| Treatment Success Rate at Week 72 | Week 72 | Proportion of participants achieving treatment success at Week 72, based on predefined criteria. |
| Sputum Culture Conversion Rates at Multiple Time Points | Up to Week 72 | Proportion of participants achieving sputum culture conversion at Weeks 8, 12, 16, 20, 36, 48, 60, and 72. |
Countries
China
Contacts
Primary ContactNaihui Chu, MD
Backup ContactZhao Jie, Ph.D
Outcome results
None listed