A Phase II Study Evaluating Fostamatinib for Hospitalized Adults With COVID-19
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 59
- 试验地点
- 2
- 主要终点
- Number of Participants With at Least 1 Serious Adverse Event
研究概览
简要总结
Background:
COVID-19 is a new disease caused by SARS-CoV-2 that was identified in 2019. Some people who get sick with COVID-19 become ill requiring hospitalization. There are some medicines that may help with recovery. Researchers want to see if a drug called fostamatinib may help people who are hospitalized with COVID-19.
Objective:
To learn if fostamatinib is safe in patients who are hospitalized with COVID-19 and gain earlier insight into whether it improves outcomes.
Eligibility:
Adults age 18 and older who are hospitalized with COVID-19.
Design:
Participants will be screened with a physical exam, including vital signs and weight. They will have a blood test and chest x-ray. They will have a COVID-19 test as a swab of either the back of the throat or the back of the nose. They will take a pregnancy test if needed.
Participants will be randomly assigned, to take either fostamatinib pills or a placebo twice daily for up to 14 days in addition to standard of care for COVID-19. If they can swallow, they will take the pills by mouth with water. If they cannot swallow or are on mechanical ventilation, the pills will be crushed, mixed with water, and given through a tube placed through the nostril, or placed in the mouth, down the esophagus, and into the stomach. Blood samples will be taken daily. Participants will return to the Clinical Center for safety follow-up visits. At these visits, they will have a physical exam and blood tests. If they cannot visit the Clinical Center, they will be contacted by phone or have a telehealth visit.
Participation will last for about two months
详细描述
Coronavirus Disease 2019 (COVID-19) is the disease caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). SARS-CoV-2 primarily infects the upper and lower respiratory tract and can lead to acute respiratory distress syndrome (ARDS) in a subset of patients with a known high mortality rate. Additionally, some patients develop other organ dysfunction including myocardial injury, acute kidney injury, shock along with endothelial dysfunction and subsequently micro and macrovascular thrombosis.
Much of the underlying pathology of SARS-CoV-2 is thought to be secondary to a dysregulated immune response and more recently a hypercoagulable state leading to immunothrombosis. Currently, two therapies have shown efficacy in large multicenter trials for the treatment of COVID-19, one of which is an antiviral (remdesivir) and the other is an immunosuppressant corticosteroid meant to dampen the immune response (dexamethasone).
Spleen tyrosine kinase (SYK) is a cytoplasmic tyrosine kinase involved in the intracellular signaling pathways of many different immune cells. In this pilot study we propose to use fostamatinib (an SYK inhibitor) as a targeted therapy for the immunological complications of hospitalized patients with COVID-19. The biological mechanisms by which SYK inhibition may improve outcomes in patients with COVID-19 include the inhibition of pro-inflammatory cytokines by monocytes and macrophages, decreased production of neutrophil extracellular traps (NETs) by neutrophils, and inhibition of platelet aggregation; three pathways that are mediated through Fc receptors (FcR) recognition of antigen-antibody complexes or activation of c-type lectin receptors (CLEC).
This is a randomized, double-blind, placebo-controlled trial of fostamatinib for the treatment of hospitalized patients with COVID-19.
We will randomly assign fostamatinib or matched placebo (1:1) to 60 eligible COVID-19 patients who are a 5 to 7 on the 8-point scale (requiring supplemental oxygen via nasal canula or noninvasive ventilation, requiring mechanical ventilation or extracorporeal membrane oxygenation).
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Intervention
fostamatinib in combination with standard of care (SOC) for the treatment of COVID-19
干预措施: fostamatinib (Drug)
Intervention - Placebo
Placebo in combination with standard of care (SOC) for the treatment of COVID-19
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With at Least 1 Serious Adverse Event
时间窗: Day 29
Number of participants with at least 1 serious adverse event by day 29 using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. CTCAE is a list of common adverse event (AE) terms. Each AE term is defined and accompanied by a grading scale (1 to 5) that indicates the severity of the AE. Grading ranges from Grade 1 which is mild to Grade 5 which is death.
次要结局
- Number of Participants With Sustained Recoveries Defined by Ordinal Scale Score of 3 or Less(day 29)
- Number of Participants Who Progress to Mechanical Ventilation(day 29)
- Number of Participants With Cumulative Clinical Endpoint of Death(day 14, day 28, day 60)
- Number of Grade 3 and 4 Adverse Events Through Day 60(Day 60)
- Participant Score on Ordinal Scale(Day 15, Day 29)
- Change in C-Reactive Protein Levels From Baseline(Day 3, Day 5, Day 8, Day 11, Day 15, Day 29)
- Change in Fibrinogen Levels From Baseline.(Day 3, Day 5, Day 8, Day 11, Day 15, Day 29)
- Change in D-Dimer Levels From Baseline(Day 3, Day 5, Day 8, Day 11, Day 15, Day 29)
- Relative Change in SpO2/FiO2 Ratio(Day 3, Day 5, Day 8, Day 11, Day 15, Day 29)
- Change in SOFA Score From Baseline(Day 3, Day 5, Day 8, Day 11, Day 15, Day 29)
- Median Days on Participants Received Supplemental Oxygen(day 29)
- The Number of Participants That Experienced Acute Renal Failure(day 29)
- Number of Participants That Experienced a Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE)(day 29)
- Change in Ferritin Levels From Baseline(Day 3, Day 5, Day 8, Day 11, Day 15, Day 29)
- Change in Interleukin 6 (IL6) Levels From Baseline(Day 3, Day 5, Day 8, Day 11, Day 15, Day 29)
- Median Days Participants Were Admitted to Intensive Care Unit(Day 29)
- Change in Absolute Lymphocyte Count Levels From Baseline(Day 3, Day 5, Day 8, Day 11, Day 15, Day 29)
- Change in Absolute Neutrophil Count Levels From Baseline(Day 3, Day 5, Day 8, Day 11, Day 15, Day 29)
- Change in Platelet Count Levels From Baseline(Day 3, Day 5, Day 8, Day 11, Day 15, Day 29)