COVID-19 and Anti-CD14 Treatment Trial

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of the Effect of Anti-CD14 Treatment in Hospitalized Patients With COVID-19

Conditions
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Coronavirus Disease 2019 (COVID-19), Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Intervention / Treatment
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* Biological: anti-CD14
* Other: Placebo
* Drug: remdesivir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, Double-Blind, Placebo-Controlled
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: anti-CD14 + SOC<br>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. | Biological: anti-CD14<br>* 4 mg/kg on Day 1, 2 mg/kg on Days 2-4 administered intravenously (IV)<br>* Other names: IC14;Drug: remdesivir<br>* Remdesivir administered intravenously for 5 days beginning with a 200 mg loading dose on Day 1, followed by 100 mg/day on Days 2-5.<br>* Other names: Veklury®;|
| Placebo Comparator: Placebo + SOC<br>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. | Other: Placebo<br>* Placebo administered intravenously on Days 1-4<br>* Other names: Placebo for anti-CD14;Drug: remdesivir<br>* Remdesivir administered intravenously for 5 days beginning with a 200 mg loading dose on Day 1, followed by 100 mg/day on Days 2-5.<br>* Other names: Veklury®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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: Not hospitalized, no limitations on activities Not hospitalized, limitation on activities and/or requiring home oxygen Hospitalized, not requiring supplemental oxygen-no longer requires ongoing medical care Hospitalized, not requiring supplemental oxygen-requiring ongoing medical care (COVID-19-related or otherwise) Hospitalized, requiring supplemental oxygen Hospitalized, on non-invasive ventilation or high-flow oxygen devices Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Death | Within the 28 day period following baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days Alive and Free of Any Episodes of Acute Respiratory Failure Through Day 28 | Episodes of acute respiratory failure are defined as by need for the following oxygen delivery resources: High-flow nasal cannula (flow rates ≥30L/min with FiO2 ≥0.4) Noninvasive positive-pressure ventilation through nasal or face mask, or nasal plugs Endotracheal intubation and mechanical Extracorporeal membrane oxygenation | Within the 28 day period following baseline. | 
| Change in the Ordinal Scale From Baseline to Day 14 | A larger negative change indicates a greater improvement in clinical status from baseline. The Eight-Point Ordinal Scale is an assessment of the clinical status on each study day (1 is best, 8 is worst). The Scale is defined as follows: Not hospitalized, no limitations on activities. Not hospitalized, limitation on activities and/or requiring home oxygen. Hospitalized, not requiring supplemental oxygen; no longer requires ongoing medical care. Hospitalized, not requiring supplemental oxygen; requiring ongoing medical care (COVID-19-related or otherwise). Hospitalized, requiring supplemental oxygen. Hospitalized, on non-invasive ventilation or high-flow oxygen devices. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO). Death. | Within the 14 day period following baseline. | 
| Change in Ordinal Scale From Baseline to Day 28. | A larger negative change indicates a greater improvement in clinical status from baseline. The Eight-Point Ordinal Scale is an assessment of the clinical status on each study day (1 is best, 8 is worst). The Scale is defined as follows: Not hospitalized, no limitations on activities. Not hospitalized, limitation on activities and/or requiring home oxygen. Hospitalized, not requiring supplemental oxygen; no longer requires ongoing medical care. Hospitalized, not requiring supplemental oxygen; requiring ongoing medical care (COVID-19-related or otherwise). Hospitalized, requiring supplemental oxygen. Hospitalized, on non-invasive ventilation or high-flow oxygen devices. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO). Death. | Within the 28 day period following baseline. | 
| Ordinal Scale Value on Day 14. | The Eight-Point Ordinal Scale is an assessment of the clinical status on each study day (1 is best, 8 is worst). The Scale is defined as follows: Not hospitalized, no limitations on activities. Not hospitalized, limitation on activities and/or requiring home oxygen. Hospitalized, not requiring supplemental oxygen; no longer requires ongoing medical care. Hospitalized, not requiring supplemental oxygen; requiring ongoing medical care (COVID-19-related or otherwise). Hospitalized, requiring supplemental oxygen. Hospitalized, on non-invasive ventilation or high-flow oxygen devices. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO). Death. | Day 14 following baseline. | 
| All-Cause Mortality Through Day 28. | Mortality due to all causes during the observation period. | Within the 28 day period following baseline. | 
| All-Cause Mortality Through Day 60. | Mortality due to all causes during the observation period. | Within the 60 day period following baseline. | 
| Percentage of Participants Alive and Free of Any Episode of Acute Respiratory Failure Through Day 28 | Episodes of acute respiratory failure are defined as by need for the following oxygen delivery resources: High-flow nasal cannula (flow rates ≥30L/min with FiO2 ≥0.4) Noninvasive positive-pressure ventilation through nasal or face mask, or nasal plugs Endotracheal intubation and mechanical ventilation Extracorporeal membrane oxygenation | Within the 28 day period following baseline. | 
| Days Alive and Free of Invasive Mechanical Ventilation Through Day 28 | Endotracheal intubation and mechanical ventilation. | Within the 28 day period following baseline. | 
| Percentage of Participants Alive and Free of Invasive Mechanical Ventilation Through Day 28 | Endotracheal intubation and mechanical ventilation. | Within the 28 day period following baseline. | 
| Percentage of Participants Alive and Discharged From the Hospital Through Day 28 | Participants must be alive and discharged from hospital. | Within the 28 day period following baseline. | 
| Percent of Participants Who Begin Corticosteroid Therapy for Worsening COVID-19 Illness After Randomization | Initiation of corticosteroid therapy. | Within the 28 day period following baseline. | 
| Serious Adverse Events (SAEs) | Number of serious adverse events | Within the 28 day period following baseline. | 
| Adverse Events (AEs) | Number of Grade 3 and 4 clinical and/or laboratory adverse events | Within the 28 day period following baseline. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anti-CD14 (anti-CD14 chimeric monoclonal antibody), randomized double-blind placebo-controlled clinical trial, hospitalized patients