A Pilot Study to Assess the Safety, Tolerability and Efficacy of Selectin Inhibitor Uproleselan (GMI-1271) in Patients With COVID-19 Pneumonia
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Safety of Uproleselan - as Measured by Serious Adverse Events
研究概览
简要总结
The purpose of this study is to find out whether the drug uproleselan can help patients with severe COVID-19 pneumonia. Investigators will study both the side effects of the drug and assess if the drug will help patients recover more quickly and slow down the progression of acute respiratory failure.
详细描述
Soluble E-selectin is a significant biomarker for adult respiratory distress syndrome (ARDS). Soluble E-selectin also has pro-inflammatory properties further releasing cytokines and promoting its synthesis and the continued influx of neutrophils. Small molecule glycomimetic antagonists of E-selectin (rivipansel and uproleselan) are 500- to 1000-fold more potent inhibitors of E-selectin and have shown activity and no measurable toxicity in human clinical trials for other indications. Treatment with these E-selectin inhibitors reduced the levels of soluble E-selectin in the bloodstream which occurs during recovery of ARDS. Thus, antagonists of E-selectin which include glycomimetic antagonists and more specifically, rivipansel (GMI-1070) and uproleselan (GMI-1271), may be used to treat COVID-19 patients with respiratory symptoms that may lead to ARDS
Primary Objective:
Safety of uproleselan in patients with severe COVID-19 pneumonia.
Secondary Objectives:
To evaluate if treatment with uproleselan administered intravenously in addition to the best available therapy according to institutional guidelines is able to reduce the progression of acute respiratory failure, in patients with severe COVID-19 pneumonia.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented COVID-19 pneumonia: defined as upper respiratory tract specimen (nasopharyngeal swab (NPS) or viral throat swab) positive for COVID-19 and/or imaging at computed tomography scan suggestive of COVID-19 pneumonia.
- •Confirmed coronavirus (SARS-CoV-2) (positive real-time reverse transcription polymerase chain reaction test (RT-PCR) for SARS-CoV-2 within 72 hours) enrolled ≤ 48 hours of need for supplemental oxygen.
- •Currently hospitalized requiring supplemental oxygen.
- •Have severe COVID-19 according to the World Health Organization (WHO) Interim Guidance with confirmation by real-time RT-PCR assay. The enrollment criteria with one of the following: respiratory distress, respiratory rate (RR) ≥30 beats/min; oxygen saturation level less than 93% in resting state; or partial pressure of oxygen (PaO2)/oxygen concentration (FiO2) ≤ 300 mmHg.
- •Willing and able to participate in all required evaluations and procedures.
排除标准
- •In the opinion of at least two investigators, unlikely to survive for >48 hours from screening.
- •Severe chronic respiratory disease (e.g. Chronic obstructive pulmonary disease or other) requiring supplemental oxygen and/or having required mechanical ventilation pre-COVID-19 infection.
- •Concurrent enrollment in a COVID related interventional drug trial. Use of remdesivir, steroids, and convalescent plasma are permitted along with other standard of care therapies for COVID.37
- •Currently on invasive mechanical ventilation.
- •Hypotension defined as systolic blood pressure < 90 mmHg on two sequential readings at least 4 hours apart.
- •Total Bilirubin ≤ 3 x upper limit of normal (ULN), Creatinine Clearance ≥ 30 mL/min/1.73m
- •Pregnant or breastfeeding.
- •Known diagnosis of an acute thrombosis on admission.
- •Concurrent dual antithrombotic therapy (aspirin or P2Y12 inhibitor plus anticoagulation to treat deep venous thrombosis or pulmonary embolism (single antiplatelet or anticoagulant agent at prophylactic dose is permitted).
- •Concomitant use of thrombolytic therapy.
- •Concomitant therapeutic systemic anticoagulant therapy (e.g. heparin, warfarin, direct thrombin inhibitors and direct factor Xa inhibitors). As per NIH Guidelines: Hospitalized adults with COVID-19 should receive Venous thromboembolism (VTE) prophylaxis per the standard of care for other hospitalized adults (AIII). Anticoagulant or antiplatelet therapy should not be used to prevent arterial thrombosis outside of the usual standard of care for patients without COVID-19 (AIII); https://www.covid19treatmentguidelines.nih.gov/therapeutic-management/
- •History of recent major bleeding, defined in accordance with the criteria of the International Society on Thrombosis and Hemostasis (ISTH).
- •History of bleeding disorder thought to impose excessive bleeding risk as per investigator discretion
- •Hemodynamic instability, defined as inability to maintain mean arterial pressure.
- •Hypersensitivity to the active substance or to any of the excipients of uproleselan.
- •Any physical examination findings and/or history of any illness that, in the opinion of the investigator, might confound the results of the study or pose an additional risk to the patient by their participation in the study
研究组 & 干预措施
Uproleselan
Uproleselan injection is a sterile solution for IV administration, supplied in single-dose vials at a concentration of 50 mg/mL.
干预措施: Uproleselan (Drug)
结局指标
主要结局
Safety of Uproleselan - as Measured by Serious Adverse Events
时间窗: Up to 28 days
Descriptive statistics will be calculated for quantitative safety data
Safety of Uproleselan- as Measured by Frequency of Serious Adverse Events
时间窗: Up to 28 days
Frequency counts will be compiled for classification of qualitative safety data.
次要结局
- Time to Change Oxygenation(during hospitalization; hospital stay ranged from 2 to 10 days)
- Number of Patients Requiring Mechanical Ventilation(Up to 28 days)
- Change in the World Health Organization (WHO) COVID-19, "8-point Ordinal Scale" as Shown by Presenting Selected Time Points Through Day 28(Enrollment, day 28)
- Actual Duration of Hospitalization(Up to 28 days)
- Actual Duration of ICU Care(Up to 28 days)
- Participants Who Experienced Grade 3-4 Hemorrhagic Events(Up to 28 days)
- Change in the Progression to Acute Respiratory Failure for Patients With a Baseline PaO2/FiO2 >= 200(Enrollment, 15 days)
- Number of Patients Alive Who Are Free of Respiratory Failure(Up to 28 days)
- All-cause Mortality(Up to 28 days)
- Change in E-selectin Plasma Concentrations, as Shown by Values for Each of Those Days(6 Days)
- Participants Who Experienced Venous Thromboembolism (Deep Venous Thrombosis or Pulmonary Embolism)(Enrollment, up to day 28)
- Number of Mechanical Ventilation and Vasopressor Days(Up to Day 28)
研究者
Lena Napolitano, MD
Medical Director and Professor of Surgery
University of Michigan