A Randomized, Open-Label, Controlled, Phase II Study to Evaluate the Safety, Tolerability and Efficacy Of S-1226 In Hospitalized Subjects With Moderate Severity Covid-19 Bronchiolitis/Pneumonia
试验速览
- 阶段
- 2 期
- 状态
- 暂停
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Treatment Emergent Adverse Effects
研究概览
简要总结
This is a randomized, open-label, controlled, Phase II proof of concept study to evaluate the safety, tolerability and efficacy of S-1226 in which hospitalized subjects (n≤30) with moderate severity COVID-19 Bronchiolitis/Pneumonia will be enrolled. The safety and tolerability of S-1226 composed of PFOB with ascending doses of carbon dioxide (4%, 8%, and 12% CO2) administered twice daily will be assessed subjects in hospitalized subjects with moderate severity COVID-19 Bronchiolitis/Pneumonia.
详细描述
This is a randomized, open-label, controlled, Phase II proof of concept study to evaluate the safety, tolerability and efficacy of S-1226 in which hospitalized subjects with moderate severity COVID-19 Bronchiolitis/Pneumonia.
S-1226 contains a potent, safe and well-tolerated bronchodilator gas (extrinsic carbon dioxide or CO2) and perflubron (PFOB), a synthetic surfactant that facilitates restoration of surfactant function and mucus clearance. The inhaled S-1226 combination of gas, vapour and liquid aerosol penetrates obstructed airways, resulting in rapid bronchodilation, enhanced blood oxygenation, improved mucus clearance and reduction of work of breathing
The primary objective of this study is to evaluate the safety and tolerability of S-1226 composed of perflubron (PFOB) with ascending doses of carbon dioxide (4%, 8% and 12% CO2) in hospitalized subjects with moderate severity COVID-19 bronchiolitis/pneumonia. The secondary objective is to establish proof of concept that S-1226 is effective in restoring lung function in hospitalized subjects with moderate severity COVID-19 bronchiolitis/pneumonia.
The study will consist of three parts: screening period, Dosing and evaluation, follow up period.
- During the screening period, subjects will undergo safety assessments and their eligibility to participate will be confirmed. Eligible subjects will then be randomly assigned to either the treatment arm (S-1226 + Standard of Care arm) or the non-treatment arm (Standard of Care only).
- The dosing and evaluation period will take place over 5 days of with two doses per day. Subjects who are randomized to receive S-1226 will be started on a dose level of S-1226 (4%). If tolerated, subjects will progress from 4%, followed by 8%, and then 12%. The highest tolerated dose will then be used for the remainder of the treatment period. All doses incorporate 3mL PFOB and will be administered over a 3-4 minute treatment period. Any enrolled subject randomized to receive S-1226 will not be required to interrupt any SOC treatment which includes supplementary oxygen.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must meet the following criteria to be included in the study:
- •Male or Females between 18-80 years of age at the time of consent.
- •Laboratory-confirmed COVID-19 infection
- •Hospitalized for COVID-19 with clinical evidence of respiratory involvement, including at least one of the following:
- •Symptoms/Signs: cough, respiratory distress, increased work of breathing
- •Radiology: Chest radiograph or other chest imaging demonstrating one of bronchial thickening, increased secretions, hyperinflation, infiltrates
- •Hypoxemia in room air, SpO2 ≤ 90%
- •Patient belongs to one of the following two categories in the seven-point COVID-19 severity scale:
- •Requiring supplemental oxygen by nasal prongs - Level 4 of the seven-point COVID-19 severity scale;
- •Requiring nasal high-flow oxygen therapy,- limited to this one component of Level 5 of the seven-point COVID-19 severity scale.
- •For women of childbearing potential involved in any sexual intercourse that could lead to pregnancy: Negative pregnancy test and willingness to use contraceptive (consistent with local regulations) during the study period.
- •Ability to sign informed consent or, when patient is not capable of doing so, informed consent can be signed by legal/authorized representative
排除标准
- •Subjects to whom any of the following applies will be excluded from the study:
- •Pregnant or breastfeeding females.
- •Patients unable to receive S-1226; particularly if receiving oxygen therapy by face mask or non invasive ventilatory support
- •Patient requires Extracorporeal Membrane Oxygenation (ECMO) and/or invasive mechanical ventilation
- •Presence of any of the following abnormal laboratory values at screening:
- •Absolute neutrophil count (ANC) less than 0.5 x 109 / L.
- •Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) greater than 5 x upper limit of normal (ULN).
- •Platelets less than 50 x109 / L.
- •In the opinion of the investigator, progression to death is imminent and inevitable within the next 72 hours, irrespective of the provision of treatment.
- •Subject, who in the opinion of the Investigator, is unsuitable to participate
研究组 & 干预措施
Standard of Care(SOC) + S-1226 at either 4% 8% or 12% CO2
Subjects will receive SOC plus the highest tolerated dose of S-1226 at either 4% 8% or 12% CO2 twice daily for up to 5 consecutive days.
干预措施: S-1226 (Drug)
结局指标
主要结局
Treatment Emergent Adverse Effects
时间窗: up to 28 days
The number and percent of treatment emergent adverse events will be monitored, recorded and graded for severity and assigned attribution. The severity will be assessed in the following manner: Mild: Awareness of signs or symptoms, but are easily tolerated and are of minor irritant type, causing no limitations of usual activities. Signs or symptoms may require minor action or additional therapy. Moderate: Discomfort severe enough to cause some limitations of usual activities and may require action or additional therapy. Severe: Incapacitating with inability to carry out usual activities and requires specific action and/or medical attention. Note: the term severe is not the same as "serious", which is based on subject/event outcome or action criteria usually associated with events that pose a threat to a subject's life or functioning. Seriousness (not severity) serves as a guide for defining regulatory reporting obligations.
次要结局
- Mean change on a 7-point ordinal scale(up to 28 days)
- Time to progression to levels 6-7 of the 7-point Ordinal Scale(up to 28 days)
- Change in use of supplemental oxygen therapy(up to 28 days)
- Normalization of body temperature, measured in degrees Celsius.(up to 28 days)
- Evaluation of changes in an SpO2/FiO2 ratio(up to 28 days)
- Normalization of oxygen saturation, SpO2 > 90%, while breathing room air, sustained minimum 24 hours(up to 28 days)
- Change in daily symptom monitoring assessed by yes or no questions to a list of symptoms.(up to 6 days)
- Days of hospitalization attributable to COVID-19 disease(up to 28 days)
- Proportion of patients that progress to levels 6-7 of the 7-point Ordinal Scale(up to 28 days)
- Time to normalization of oxygen saturation, SpO2 > 90%, while breathing room air sustained minimum 24 hours.(up to 28 days)