A Phase 2 Study to Evaluate the Early Bactericidal Activity, Safety and Tolerability of Nebulised RESP301 in Adults With Newly Diagnosed, Rifampicin Susceptible Pulmonary Tuberculosis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Early Bactericidal Activity (EBA) of Inhaled RESP301 Measured as Time to Positivity (TTP)
研究概览
简要总结
A Phase 2, Single-Centre, Open-Label, Parallel Control Arm, Randomised Clinical Study to Evaluate the Early Bactericidal Activity (EBA), Safety and Tolerability of Nebulised RESP301 in Adults with Newly Diagnosed, Rifampicin Susceptible Pulmonary Tuberculosis
详细描述
A total of approximately 15 participants will be recruited per treatment arm (total of approximately 75 participants in the study). Control arm participants will be split across sequential stages stages 1 and 2, with no stratification.
Stage 1: To determine the EBA of
- Treatment Arm 1 (Active; n = 15) - inhaled RESP301 6 ml dosed via nebulisation administered three times daily over 14 days
- Treatment Arm 2 (Control; n= 5) - HRZE taken orally once daily
On completion of Stage 1, recruitment will be paused and an interim analysis performed to determine whether the study should proceed to Stage 2.
Stage 2: To determine the EBA of
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
- Single (Outcomes Assessor)
盲法说明
Microbiology staff will be blinded to treatment allocation.
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
- •Provide written, informed consent prior to all study-related procedures and agree to undergo all study procedures
- •Body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive
- •Newly diagnosed pulmonary TB
- •Rifampicin susceptible pulmonary TB as determined by molecular testing
- •Ability to produce an adequate volume of sputum as estimated from a pre-treatment overnight sputum collection sample (estimated 10 ml or more)
- •Spirometry performed during screening with a FEV1 of ≥ 40%
- •Be of non-childbearing potential or willing to use effective methods of contraception
排除标准
- •HIV positive AND CD4 < 350 cells/mm3 OR are receiving antiviral therapy (ART)
- •Methaemoglobin saturation (SpMet) >3%
- •Female participant who is pregnant or breast-feeding
- •Participants planning to conceive a child within the anticipated period of study participation and for at least 90 days after the last dose of IMP in the study
- •Participation in other clinical studies with investigational agents within 8 weeks prior to screening
- •Treatment received for this episode of TB with any drug active against M.tb
- •Treatment with immunosuppressive medications such as TNF-alpha inhibitors within 2 weeks prior to screening, or systemic corticosteroids for more than 7 days within 2 weeks prior to screening.
- •Treatment with nitric oxide and other nitric oxide donor agents, phosphodiesterase inhibitors and lung surfactant drugs, within 30 days prior to screening
研究组 & 干预措施
1 (Active)
Inhaled RESP301 6ml via nebulisation three times daily
干预措施: RESP301 (Drug)
2 (Control)
HRZE taken orally once daily
干预措施: HRZE (Drug)
3 (Active)
Inhaled RESP301 6 ml via nebulisation once daily
干预措施: RESP301 (Drug)
4 (Active)
Inhaled RESP301 6 ml via nebulisation twice daily
干预措施: RESP301 (Drug)
5 (Active)
Inhaled RESP301 6 ml via nebulisation three times daily plus HRZE taken orally once dialy
干预措施: RESP301 (Drug)
5 (Active)
Inhaled RESP301 6 ml via nebulisation three times daily plus HRZE taken orally once dialy
干预措施: HRZE (Drug)
结局指标
主要结局
Early Bactericidal Activity (EBA) of Inhaled RESP301 Measured as Time to Positivity (TTP)
时间窗: 0-2, 0-7, 0-14, 0-15 and 14-15 days
Overnight sputum collection from which viable mycobacteria in the sample is quantified as TTP Observed EBA for 0-2, 0-7, 0-14, 0-15 and 14-15 days in TTP (hours) for treatment in each of the treatment groups
次要结局
- Early Bactericidal Activity (EBA) of Inhaled RESP301 Measured as Colony Forming Units (CFU)(0-2, 0-7, 0-14, 0-15 and 14-15 days)
- Safety and Tolerability of Inhaled RESP301 Measured as Number of Treatment Emergent Adverse Events (TEAEs)(Stage 1: Dosing period 14 days + Follow-up period 14 days. Stage 2: Participants did not enter the treatment phase due to early study termination)