Chu Naihui, Nie Wenjuan, Du Juan, Wang Manni, Ma Liping, Wang Qingfeng, Wang Jun, Hu Xiaomeng, Wu Jin, Lu Yu, Huang Mailing, Wei Yuquan, Wang Zhenling, He Jian-Qing, Ding Zhenyu, Wei Xiawei
Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China.
Wuhan Pulmonary Hospital (Wuhan Institute for Tuberculosis Control), Wuhan, Hubei, China.
Signal Transduct Target Ther. 2025 Dec 30;10(1):427. doi: 10.1038/s41392-025-02517-z.
Tuberculosis (TB) is a contagious disease that threatens human health worldwide. Combination chemotherapy is usually recommended for this disease. Recently, 2 nitroimidazole-based agents, namely, delamanid and pretomanid, have been approved by regulatory agencies. JDB0131 is a novel, structurally optimized third-generation nitroimidazole antituberculosis agent that incorporates the advantages of earlier compounds. This multicenter, prospective, randomized phase 2a trial was conducted to evaluate its efficacy and safety in patients with tuberculosis (NCT06224036). In total, 52 patients with newly diagnosed TB were recruited. JDB0131 was tested in a dose escalation manner (cohort 1: 100 mg bid, cohort 2: 200 mg qd, and cohort 3: 200 mg bid). For comparison, delamanid (100 mg bid) and classic fixed-dose combination (FDC) regimens were included as controls. The primary endpoint was logarithmic changes in the number of colony formation units (CFUs) in the solid media culture of sputum TB (log10 CFU). The early bactericidal activity (EBA) of JDB0131 was better than that of delamanid. During the time interval between days 0 and 14, JDB0131 at a dose of 200 mg bid (cohort 3) showed superior efficacy over delamanid. At the end of drug intervention (day 14), JDB0131 (all 3 dose levels) achieved superior time to positivity (TTP) over delamanid. Ninety-one adverse events (AEs), including no serious AEs, were attributed to JDB0131 in 30 patients. This trial identified a promising new drug for the increasing TB burden worldwide.
结核病（TB）是一种在全球范围内威胁人类健康的传染病。通常推荐采用联合化疗来治疗这种疾病。最近，两种基于硝基咪唑的药物，即地拉曼宁和普瑞马尼德，已获监管机构批准。JDB0131是一种新型的、结构优化的第三代硝基咪唑类抗结核药物，它融合了早期化合物的优点。这项多中心、前瞻性、随机2a期试验旨在评估其在结核病患者中的疗效和安全性（NCT06224036）。总共招募了52例新诊断的结核病患者。JDB0131以剂量递增的方式进行测试（队列1：100毫克，每日两次；队列2：200毫克，每日一次；队列3：200毫克，每日两次）。作为对照，纳入了地拉曼宁（100毫克，每日两次）和经典固定剂量联合（FDC）方案。主要终点是痰结核菌固体培养基培养中菌落形成单位（CFU）数量的对数变化（log10 CFU）。JDB0131的早期杀菌活性（EBA）优于地拉曼宁。在第0天至第14天的时间间隔内，200毫克，每日两次剂量的JDB0131（队列3）显示出比地拉曼宁更优的疗效。在药物干预结束时（第14天），JDB0131（所有3个剂量水平）的阳性时间（TTP）优于地拉曼宁。30例患者中共有91例不良事件（AE）归因于JDB0131，其中无严重不良事件。这项试验为全球日益增加的结核病负担确定了一种有前景的新药。
