A proof-of Concept Study of the Use of Janus Kinase 1 and 2 Inhibitor, Baricitinib, in the Treatment of COVID-19-related Pneumonia
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 13
- 主要终点
- Response to treatment: survival
研究概览
简要总结
The objective of the study is to assess the efficacy and safety of Baricitinib in the treatment of patients with COVID-19 pneumonia.
This will be a proof-of-concept trial with an exploratory single-arm proof of concept Phase IIa study to assess the efficacy and safety profile of Baricitinib in a limited number of patients with severe acute respiratory syndrome (SARS)-CoV-2 pneumonia. If the initial proof of concept phase will lead to favourable results, an open-label, Phase II, randomized controlled trial will be then designed and performed to confirm the results obtained in the proof of concept phase. The proof-of-concept phase guarantees that no safety issues arise on a limited number of patients in the use of a drug new to the current condition being treated.
详细描述
Baricitinib 4 mg/daily will be prescribed for 7 days to eligible patients showing signs of acute inflammatory response activation. The primary outcome of the study will be the response to treatment. A patient is considered responder in the absence of either moderate to severe oxygenation impairment or death, whichever occurs first, within 8 days from enrolment. The main secondary outcomes will include the responder rate and mortality at 15 days, the quantification of patients experiencing moderate to severe oxygenation impairment, rate of patients admitted to the intensive care unit, length of hospitalization, mortality at 28 days, rate of re-admission, and adverse events. The duration of the study will be 28 days. In the proof of concept phase, 13 patients will be enrolled; if the responders will be at least 4 patients without safety issues, Baricitinib will be considered for further studies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ability to obtain informed patient consent noting the limitations of existing knowledge regarding Baricitinib's efficacy and the labeled warning and precautions as the proposed use is outside the approved indication, as well as the presence of known risk of being treated with Baricitinib while the subject of an active infection
- •informed Consent as documented by signature
- •patients with a confirmed SARS-CoV-2 pneumonia
- •adult patients aged 18-74 years old
- •infiltrates at chest radiography
- •c-reactive protein level greater than 10 mg/dl or ferritin level > 900 ug/L
- •Lymphocyte count less than 1500/mmc
- •> 200 PaO2/FiO2 ≤ 300
排除标准
- •patients aged < 18 years old and ≥ 75 years old
- •concomitant bacterial infection
- •lymphopenia less than 500/mmc
- •hemoglobin < 8 g/dl
- •absolute neutrophil count < 1 x 109 cells/L
- •requiring continuous positive airway pressure (C-PAP) or mechanical ventilation
- •sudden clinical deterioration requiring intensive care unit access
- •known hypersensitivity or allergy to the study drug
- •Creatinine clearance < 30 mL/min; if the creatinine clearance is between 30 and 60 mL/min the dose of Baricitinib should be reduced to 2 mg/daily
- •Severe hepatic impairment (no dose adjustment of Baricitinib is required in mild or moderate hepatic impairment)
- •Pregnant or breast-feeding
- •Active tuberculosis
- •Evidence of active hepatitis B (HBV) (HbsAg positive) or with detectable hepatitis C virus (HCV)-RNA, human immunodeficiency virus (HIV)
- •Ongoing, acute diagnosis of deep venous thrombosis/pulmonary embolism (DVT/PE)
- •Previous diagnosis of DVT/PE
研究组 & 干预措施
Baricitinib active treatment
Baricitinib 4 mg/day
干预措施: Baricitinib (Drug)
结局指标
主要结局
Response to treatment: survival
时间窗: 8 days
Absence of death within 8 days from enrollment
Response to treatment: absence of moderate to severe oxygenation impairment (Berlin criteria)
时间窗: 8 days
A patient is consider responder in the absence of either moderate to severe oxygenation impairment according to Berlin criteria - measured as Partial pressure of oxygen/fraction inspired oxygen (PaO2/FiO2)
次要结局
- To measure the length of hospital stay(8 days; 15 days)
- 28-day mortality(28 days)
- TNFalpha; vascular endothelial growth factor (VEGF); interferon gamma (IFNgamma) levels(15 days)
- To quantify the rate of each of: moderate or severe oxygenation impairment within 8 days(8 days)
- To quantify the rate of each of: moderate or severe oxygenation impairment within 15 days(15 days)
- Mortality(8 days and 15 days)
- Peripheral capillary oxygen saturation (SpO2)(8 days; 15 days)
- Partial pressure of oxygen/fraction inspired oxygen (PaO2/FiO2)(8 days; 15 days)
- To assess the rate of patients admitted to the intensive care unit(8 days; 15 days)
- To quantify the rate of re-admission within 28 days(28 days)
- To quantify the cumulative incidence and severity of adverse events(28 days)
- Interleukin (IL)-1; IL-2; IL-10; IL-6; IL-8; IL-17; IL-2 receptor levels;(15 days)
- Viral load analyses(15 days)
研究者
Carlomaurizio Montecucco
Prof
Fondazione IRCCS Policlinico San Matteo di Pavia