NCT05382312已完成2 期
A Parallel Group, Phase 2A, Randomised, Open Label Treatment Study to Assess the Early Bactericidal Activity, Safety and Tolerability of GSK3036656 Administered as a Two Drug Combination With Novel and Established Antitubercular Agents, or Standard of Care in Adults With Rifampicin-susceptible Pulmonary Tuberculosis
适应症
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 127
- 试验地点
- 2
- 主要终点
- Change from Baseline in log10 CFU of Mycobacterium tuberculosis (MTB) (per milliliters of respiratory sputum samples)
研究概览
简要总结
This study measured the early bactericidal activity (EBA), safety, tolerability and pharmacokinetics of GSK3036656 in combination with either delamanid, bedaquiline or BTZ-043 and delamanid in combination with bedaquiline or standard of care, for 14 days, in participants with newly diagnosed sputum smear positive drug-sensitive pulmonary tuberculosis. Participants reverted to the standard treatment (RIFAFOUR e-275) once the study treatment (Day 1 to Day 14) was completed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Single (Outcomes Assessor)
盲法说明
All laboratory staff involved in analyzing and reporting the microbiological endpoints (logarithm to base10 [log10] colony forming units [CFU] counts and time to sputum culture positivity) were unaware of treatment assignments.
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
- •Participants were 18 to 65 years of age inclusive, at the time of signing the informed consent.
- •Participants had:
- •A new episode of untreated, rifampicin-susceptible pulmonary tuberculosis (TB)
- •A chest X-ray picture consistent with pulmonary TB
- •At least one sputum sample positive on direct microscopy for acid-fast bacilli (at least 1+ on the International Union Against Tuberculosis and Lung Disease [IUATLD]/World Health Organization [WHO] scale) or positive on a molecular test (at least medium positive for MTB on Xpert MTB/Rif)
- •A normal echocardiogram, or an echocardiogram with normal left ventricular function with at most trace to mild valvular regurgitation, and no valvular stenosis
- •A creatinine clearance greater than or equal to (>=) 90 mL/minute (Cockcroft-Gault formula)
- •Male participants were eligible to participate if they agreed to barrier precautions until 90 days after the last dose.
- •A female participant was eligible to participate if she was not pregnant or breastfeeding and was a woman of non-childbearing potential (WONCBP) or a woman of childbearing potential (WOCBP) using a highly effective contraceptive method. A WOCBP had to have a negative urine or serum pregnancy test, as required by local regulations, before the first dose of study intervention. Only participants who were at least 25 years of age, and females of non-childbearing potential, were eligible for the positron emission tomography-computed tomography (PET-CT) assessments.
- •Participants were capable of giving signed informed consent.
排除标准
- •There was evidence of a clinically significant condition or abnormality (as judged by the Investigator) (other than the indication being studied) that might have compromised safety or the interpretation of trial efficacy or safety endpoints.
- •There was clinically significant evidence of extrathoracic TB, as judged by the Investigator.
- •QTc interval corrected for heart rate by Fridericia's formula (QTcF) was greater than (>) 450 milliseconds (msec).
- •There was arterial hypertension with systolic BP >=160 mm Hg or diastolic BP >=100 mm Hg. Participants with well-controlled hypertension could be included if they were using amlodipine for the duration of the study.
- •Participants had vitiligo.
- •Participants were receiving QT-prolonging drugs, including but not limited to fluoroquinolones, macrolides, and clofazimine.
- •HIV-infected participants who:
- •had a cluster of differentiation (CD)4+ count <350 cells/microliters;
- •had received antiretroviral therapy medication within the last 30 days;
- •had received oral or intravenous antifungal medication within the last 30 days;
- •or had an acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection or malignancy in the last 12 months (except pulmonary TB).
- •Hepatitis B surface antigen (HBsAg) was present, or the Hepatitis C antibody test result at screening was positive.
- •Participants had diabetes (Type 1 or 2), point-of-care glycated hemoglobin (HbA1c) above 6.5%, or random glucose over 11.1 millimoles (mmol)/L.
- •There were diseases or conditions in which the use of delamanid or bedaquiline was contraindicated.
- •Participants had abnormal laboratory values at screening, as graded by the enhanced Common Terminology Criteria for Adverse Events (CTCAE version 5, 2017).
结局指标
主要结局
Change from Baseline in log10 CFU of Mycobacterium tuberculosis (MTB) (per milliliters of respiratory sputum samples)
时间窗: Baseline and up to Day 14
The extended early bactericidal activity of each treatment group will be determined by the change from Baseline to Day 14 in log10CFU.
次要结局
- Change from Baseline in time to sputum culture positivity(Baseline and up to Day 14)
- Number of participants with serious adverse events(Up to Day 28)
- Number of participants with adverse events of Grade 3 severity or higher(Up to Day 28)
- Number of participants with adverse events related to study drug(Up to Day 28)
- Number of participants withdrawn from the treatment due to adverse events(Up to Day 28)
- Number of participants withdrawn from the study due to adverse events(Up to Day 28)
- Number of participants with electrocardiogram (ECG) values of potential clinical importance (PCI)(Up to Day 28)
- Number of participants with hematology laboratory values of PCI(Up to Day 28)
- Number of participants with clinical chemistry laboratory values of PCI(Up to Day 28)
- Number of participants with vital signs of PCI(Up to Day 28)
研究者
研究点 (2)
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