Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of the Effect of Anti-CD14 Treatment in Hospitalized Patients With COVID-19
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 49
- 试验地点
- 5
- 主要终点
- The Time to Clinical Recovery, Defined as the Time From Baseline to the First Day That Subject is in Categories 1, 2, or 3 on the Eight-Point Ordinal Scale Through Day 28.
研究概览
简要总结
This study aims to address the following objectives:
- To determine the efficacy of IC14, an anti-CD14 chimeric monoclonal antibody, in patients hospitalized with respiratory disease and hypoxemia due to SARS-CoV-2, in terms of improving the time to resolution of disease.
- To determine the efficacy of IC14 in reducing the severity of respiratory disease in patients hospitalized with respiratory disease due to SARS-CoV-2.
- To determine the safety of IC14 in patients hospitalized with respiratory disease due to SARS-CoV-2.
详细描述
This is a multicenter, randomized, double-blind, placebo-controlled study of IC14, an antibody to CD14, in reducing the severity of respiratory disease in hospitalized Coronavirus Disease 2019 (COVID-19) patients.
Participants will be randomized to IC14 or matching placebo and followed for 60 days after randomization. The study drug will be administered daily on Days 1-4 by intravenous infusion. All participants will receive standard of care antiviral therapy with remdesivir.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Placebo consists of identical-appearing diluent
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
- •Patients included in the study must meet all the following criteria:
- •Patient or legally authorized representative able to provide informed consent
- •Presence of SARS-CoV-2 infection documented by positive RT-PCR testing or history of positive RT-PCR test for SARS-CoV-2 within 7 days of screening
- •Radiologic findings compatible with diagnosis of SARS-CoV-2 pulmonary infection
- •Hypoxemia as defined by any of the following:
- •SpO2 ≤94% on room air, or
- •Requirement for ≥2L/m O2 per standard nasal cannula to maintain SpO2≥94%, but not requiring high-flow nasal cannula (defined as ≥30 L/m), and
- •Negative pregnancy test for women of childbearing potential and, must be willing to use birth control for the duration of the study.
排除标准
- •An individual fulfilling any of the following criteria should be excluded from enrollment in the study:
- •Receiving non-invasive positive-pressure ventilation through nasal mask, face mask, or nasal plugs
- •Receiving invasive mechanical ventilation
- •Patient, surrogate, or physician not committed to full support
- •-Exception: a participant will not be excluded if he/she would receive all supportive care other than attempts at resuscitation from cardiac arrest)
- •Anticipated survival <48 hours
- •Underlying malignancy, or other condition, with estimated life expectancy of less than two months
- •Significant pre-existing organ dysfunction prior to randomization
- •Lung: Currently receiving home oxygen therapy as documented in medical record
- •Heart: Pre-existing congestive heart failure defined as an ejection fraction <20% as documented in the medical record
- •Renal: End-stage renal disease requiring renal replacement therapy or eGFR <30 mL/min
- •Liver: Severe chronic liver disease defined as Child-Pugh Class C or AST or ALT >5x upper limit of normal
- •Hematologic: Baseline platelet count <50,000/mm^3
- •Presence of co-existing infection, including, but not limited to:
- •HIV infection not virally suppressed and with pre-hospitalization CD4 counts ≤ 500 cell/mm^3
- •Active tuberculosis or a history of inadequately treated tuberculosis
- •Active hepatitis B or hepatitis C viral infection
- •Ongoing immunosuppression
- •Solid organ transplant recipient
- •High-dose corticosteroids (equivalent to >20 mg/prednisone/day) within the past 28 days, except for dexamethasone except for dexamethasone or equivalent treatment for COVID-19 illness
- •Oncolytic drug therapy within the past 14 days
- •Current treatment, or treatment within 30 days or five half-lives (whichever is longer) with etanercept (Enbrel®), infliximab (Remicade®), adalimumab (Humira®), certolizumab (Cimzia®), golimumab (Simponi®), anakinra (Kineret®), rilonacept (Arcalyst®), tocilizumab (Actemra®), sarilumab (Kevzara®), siltuximab (Sylvant®), or other potent immunosuppressant or immunomodulatory drugs or treatments
- •Current treatment with an anti-viral medication for COVID-19 (e.g. hydroxychloroquine, lopinavir/ritonavir), other than remdesivir
- •Current enrollment in an interventional trial for COVID-19
- •History of hypersensitivity or idiosyncratic reaction to IC14
- •Women who are currently breastfeeding
- •Received a live-attenuated vaccine within 30 days prior to enrollment
- •Received five or more doses of remdesivir, including the loading dose, outside of the study as treatment for COVID-19, or
- •Any condition that in the opinion of the treating physician will increase the risk for the participant.
研究组 & 干预措施
anti-CD14 + SOC
Anti-CD14: Anticipated 150 participants randomized to 4 mg/kg on Day 1, 2 mg/kg on Days 2-4 intravenously.
Standard of Care (SOC): All participants will receive remdesivir (antiviral) according to current approved dosing for COVID-19 illness.
干预措施: remdesivir (Drug)
anti-CD14 + SOC
Anti-CD14: Anticipated 150 participants randomized to 4 mg/kg on Day 1, 2 mg/kg on Days 2-4 intravenously.
Standard of Care (SOC): All participants will receive remdesivir (antiviral) according to current approved dosing for COVID-19 illness.
干预措施: anti-CD14 (Biological)
Placebo + SOC
Anticipated 150 participants randomized to Placebo diluent on Days 1-4 intravenously.
Standard of Care (SOC): All participants will receive remdesivir (antiviral) according to current approved dosing for COVID-19 illness.
干预措施: Placebo (Other)
Placebo + SOC
Anticipated 150 participants randomized to Placebo diluent on Days 1-4 intravenously.
Standard of Care (SOC): All participants will receive remdesivir (antiviral) according to current approved dosing for COVID-19 illness.
干预措施: remdesivir (Drug)
结局指标
主要结局
The Time to Clinical Recovery, Defined as the Time From Baseline to the First Day That Subject is in Categories 1, 2, or 3 on the Eight-Point Ordinal Scale Through Day 28.
时间窗: Within the 28 day period following baseline
The Primary Endpoint is time to clinical recovery, defined as the time from baseline to the first day that a subject is in categories 1, 2, or 3 on the Eight-Point Ordinal Scale through Day 28 (range 1 \[best\] to 8 \[worst\]). The Eight-Point Ordinal Scale is an assessment of the clinical status on each study day. The Scale is defined as follows: 1. Not hospitalized, no limitations on activities 2. Not hospitalized, limitation on activities and/or requiring home oxygen 3. Hospitalized, not requiring supplemental oxygen-no longer requires ongoing medical care 4. Hospitalized, not requiring supplemental oxygen-requiring ongoing medical care (COVID-19-related or otherwise) 5. Hospitalized, requiring supplemental oxygen 6. Hospitalized, on non-invasive ventilation or high-flow oxygen devices 7. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 8. Death
次要结局
- Days Alive and Free of Any Episodes of Acute Respiratory Failure Through Day 28(Within the 28 day period following baseline.)
- Change in Ordinal Scale From Baseline to Day 28.(Within the 28 day period following baseline.)
- Ordinal Scale Value on Day 14.(Day 14 following baseline.)
- Adverse Events (AEs)(Within the 28 day period following baseline.)
- Change in the Ordinal Scale From Baseline to Day 14(Within the 14 day period following baseline.)
- All-Cause Mortality Through Day 28.(Within the 28 day period following baseline.)
- Percentage of Participants Alive and Free of Any Episode of Acute Respiratory Failure Through Day 28(Within the 28 day period following baseline.)
- Days Alive and Free of Invasive Mechanical Ventilation Through Day 28(Within the 28 day period following baseline.)
- Percentage of Participants Alive and Free of Invasive Mechanical Ventilation Through Day 28(Within the 28 day period following baseline.)
- Percentage of Participants Alive and Discharged From the Hospital Through Day 28(Within the 28 day period following baseline.)
- Percent of Participants Who Begin Corticosteroid Therapy for Worsening COVID-19 Illness After Randomization(Within the 28 day period following baseline.)
- Serious Adverse Events (SAEs)(Within the 28 day period following baseline.)
- All-Cause Mortality Through Day 60.(Within the 60 day period following baseline.)