A Phase 2, Open-Label, Multi-Group, Controlled, Randomized Trial of the Safety, Bactericidal Activity, and Pharmacokinetics of TBD09 in Combination With Other Active Agents in Adults With Drug-Sensitive Pulmonary Tuberculosis
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 150
- 试验地点
- 15
- 主要终点
- Bactericidal Activity
研究概览
简要总结
The purpose of this study is to evaluate if TBD09 in combination with other active agents in adults with drug sensitive pulmonary tuberculosis has potential to be safe and effective.
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
- None
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
- •Age 18-65 years at consent
- •Body weight 35-100 kg at screening
- •Written informed consent obtained
- •Newly diagnosed rifampicin-sensitive pulmonary TB
- •Molecular confirmation of M. tuberculosis on Xpert MTB/RIF Ultra
- •≥1+ AFB smear or Xpert Ultra low, medium, or high semi-quantitative result
- •Rifampicin sensitivity on molecular test
- •Chest X-ray consistent with TB (Investigator assessment)
- •Able to spontaneously produce sputum
- •Reproductive requirements met
- •Women of childbearing potential: 2 approved contraceptive methods or abstinence
- •Males: contraception or abstinence through 90 days post-dose
排除标准
- •Prior anti-TB treatment for the current TB episode within 60 days
- •Prior medication active against Mtb within 3 months
- •Evidence of extra-thoracic TB, per investigator judgement
- •Prior treatment completion for TB within 3 years
- •2 or more prior episodes of TB
- •Clinically significant history of or current medical condition posing safety risk
- •If HIV positive:
- •Not on ARVs or taking ARVs for <3 months prior to screening OR
- •CD4+ count <200cells/uL at screening OR
- •HIV viral load >200 copies /mL at screening OR
- •AIDS infection or malignancies
- •Meets any of the following laboratory values during screening:
- •AST, ALT, or ALP ≥2.5× ULN
- •Total bilirubin ≥1.2× ULN
- •eGFR <60 mL/min/1.73 m²
- •Hemoglobin <9.0 g/dL (male) or <8.5 g/dL (female)
- •White blood cell count <2,000/mm³
- •Absolute neutrophil count <800/mm³
- •Platelet count ≤100,000/mm³
- •Positive hepatitis B surface antigen
- •Positive hepatitis C antibody
- •HbA1c ≥8.0%
- •Current or recent systemic immunosuppressive therapy, including corticosteroids
- •Significant drug or alcohol abuse affecting compliance or safety
- •Pregnant or breastfeeding, positive pregnancy test, or planning pregnancy shortly after treatment
研究组 & 干预措施
Group 1
The combination of TBD09 (100 mg three times weekly, TIW), bedaquiline and pretomanid
干预措施: Bedaquiline, pretomanid and TBD09 (Drug)
Group 2
The combination of TBD09 (100 mg QD), bedaquiline and pretomanid
干预措施: Bedaquiline, pretomanid and TBD09 (Drug)
Group 3
The combination of TBD09 (300 mg QD), bedaquiline and pretomanid
干预措施: Bedaquiline, pretomanid and TBD09 (Drug)
Group 4
The combination of TBD09 (500 mg QD), bedaquiline and pretomanid
干预措施: Bedaquiline, pretomanid and TBD09 (Drug)
Group 5
The combination of linezolid (600 mg QD), bedaquiline and pretomanid
干预措施: Bedaquiline, pretomanid and linezolid (Drug)
结局指标
主要结局
Bactericidal Activity
时间窗: From randomization through Day 28 (EOT)
Average daily change in MGIT sputum culture TTD from baseline to end-of-treatment (EOT)
Safety: SAEs
时间窗: Screening through Day 35 (EOS)
Proportion of participants with this event
Safety: TEAEs
时间窗: Screening through Day 35 (EOS)
Proportion of participants with this event
Safety: AESIs
时间窗: Screening through Day 35 (EOS)
Proportion of participants with this event
Safety: AEs leading to treatment discontinuation
时间窗: Screening through Day 35 (EOS)
Proportion of participants with this event
次要结局
- Safety: Hematologic Effect(Randomization through Day 35 (EOS))
- Safety: Visual Acuity Assessment(Randomization through Day 35 (EOS))
- Safety: Colour Vision Assessment(Randomization through Day 35 (EOS))
- Safety: Brief Peripheral Neuropathy Screen (BPNS) score(Randomization through Day 35 (EOS))
- Bactericidal activity(Day 28 (EOT))
- Maximum plasma concentration (Cmax) of TBD09(Day 1 and Day 28)
- Time to maximum plasma concentration (Tmax) of TBD09(Day 1 and Day 28)
- Area under the curve from 0 to 24 hours (AUC0-24) of plasma concentration of TBD09(Day 1)
- Area under the curve from 0 to infinity (AUC0-inf) of plasma concentration of TBD09(Day 28)
- Area under the curve over the dosing interval on day 28 (AUCtau) of plasma concentration of TBD09(Day 28)
- Accumulation ratio (Area under the curve from 0 to the end of the dosing interval (AUCtau) / AUC0-24), Day 28 vs Day 1 of plasma concentration of TBD09(Day 1 and Day 28)