NCT02968927Unknown2 期
A Ph2 Randomized Trial to Evaluate the Safety Preliminary Efficacy and Biomarker Response of Host Directed Therapies Added to Rifabutin-modified Standard Therapy in Adults With Drug-Sensitive Smear-Positive Pulmonary TB
The Aurum Institute NPC1 个研究点 分布在 1 个国家目标入组 200 人开始时间: 2016年11月最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- SAEs and SUSARs
研究概览
简要总结
To examine the safety and preliminary efficacy of multiple adjunctive host directed TB therapies (TB HDT), to assess their potential to shorten TB treatment and/or prevent permanent lung damage.
详细描述
OBJECTIVES:
To determine the safety and preliminary efficacy of 4 TB HDT candidates:
- Safety (treatment emergent serious adverse events and SUSARs)
- Microbiologic effects in sputum (culture conversion, change in MGIT TTP) and blood (WBA)
- PET/CT imaging
- Serum markers of inflammation
- Effects on Mtb-specific and general immune function
- Pulmonary effects (spirometry, 6MWT, O2 saturation, and St. George Respiratory Symptom Questionnaire) In each case, TB HDT effects will be determined by comparison to patients treated with standard TB therapy alone with regard to a common set of primary and secondary endpoints.
PRIMARY ENDPOINTS
- For auranofin, everolimus, and vitamin D: the proportions of patients experiencing suspected unexpected serious adverse reactions (SUSARs).
- For CC-11050: the proportion of patients experiencing treatment emergent serious adverse events (SAEs).
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
- •Willing and able to provide signed written consent or witnessed oral consent in the case of illiteracy, prior to undertaking any trial-related procedures.
- •Aged 18 to 65 years, male, or if female, either not of reproductive potential (post-menopause, or status-post surgical sterilization) or with an intrauterine contraceptive device in place.
- •Body weight (in light clothing without shoes) between 40 and 90 kg.
- •First episode of pulmonary tuberculosis diagnosed by positive sputum AFB smear with subsequent culture confirmation OR positive Xpert TB/RIF with Ct <20 [4].
- •RIF susceptibility diagnosed by Xpert TB/RIF OR Hain test
- •Chest radiograph meeting criteria for moderate or far advanced pulmonary tuberculosis [5]
- •HIV-1 seronegative
- •HBsAg negative
排除标准
- •Any condition for which participation in the trial, as judged by the investigator, could compromise the well-being of the subject or prevent, limit or confound protocol specified assessments
- •Current or imminent treatment for malaria.
- •Is critically ill, and in the judgment of the investigator has a diagnosis likely to result in death during the trial or the follow-up period.
- •TB meningitis or other forms of severe tuberculosis with high risk of a poor outcome as judged by the investigator.
- •History of allergy or hypersensitivity to any of the trial therapies or related substances, including known allergy or suspected hypersensitivity to rifampin or rifabutin.
- •Having participated in other clinical trials with investigational agents within 8 weeks prior to trial start or currently enrolled in an investigational trial.
- •Subjects with any of the following at screening:
- •Cardiac arrhythmia requiring medication;
- •Prolongation of QT/QTc interval with QTcF (Fridericia correction) >450 ms;
- •History of additional risk factors for Torsade de Pointes, (e.g., heart failure, hypokalemia, family history of Long QT Syndrome);
- •Any clinically significant ECG abnormality, in the opinion of the investigator.
- •Patients requiring concomitant medications that prolong the QT inter-val.
- •Random blood glucose >140 mg/dL, or history of unstable Diabetes Mellitus which required hospitalization for hyper- or hypoglycaemia within the past year prior to start of screening.
- •Use of systemic corticosteroids within the past 28 days.
- •Subjects with any of the following abnormal laboratory values:
- •creatinine >2 mg/dL
- •haemoglobin <8 g/dL
- •platelets <100x109 cells/L
- •serum potassium <3.5
- •aspartate aminotransferase (AST) ≥2.0 x ULN
- •alkaline phosphatase (AP) >5.0 x ULN
- •total bilirubin >1.5 mg/dL
研究组 & 干预措施
2HRbEZ/4HRb
Active Comparator
2HRbZE
干预措施: 2HRbZE/4HRb (Drug)
Everolimus
Experimental
Everolimus 0.5 MG
干预措施: Everolimus 0.5 MG (Drug)
Everolimus
Experimental
Everolimus 0.5 MG
干预措施: 2HRbZE/4HRb (Drug)
Auranofin
Experimental
Auranofin 6 MG
干预措施: Auranofin 6 MG (Drug)
Auranofin
Experimental
Auranofin 6 MG
干预措施: 2HRbZE/4HRb (Drug)
Vitamin D
Experimental
Vitamin D3
干预措施: Vitamin D3 (Drug)
Vitamin D
Experimental
Vitamin D3
干预措施: 2HRbZE/4HRb (Drug)
CC-11050
Experimental
CC-11050
干预措施: CC-11050 (Drug)
CC-11050
Experimental
CC-11050
干预措施: 2HRbZE/4HRb (Drug)
结局指标
主要结局
SAEs and SUSARs
时间窗: through day 180
For auranofin, everolimus, and vitamin D: the proportions of patients experiencing suspected unexpected serious adverse reactions (SUSARs). For CC-11050: the proportion of patients experiencing treatment emergent serious adverse events (SAEs).
次要结局
- TEAEs other than SAEs and SUSARs(through day 180)
- Sputum culture status on day 56(day 56)
研究者
研究点 (1)
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