COVID-19 and Anti-CD14 Treatment Trial

Phase 2

Terminated

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

Interventions: Biological: anti-CD14
Other: Placebo
Drug: remdesivir

Registration Number: NCT04391309

Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary: This study aims to address the following objectives:

1. 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.

2. To determine the efficacy of IC14 in reducing the severity of respiratory disease in patients hospitalized with respiratory disease due to SARS-CoV-2.

3. To determine the safety of IC14 in patients hospitalized with respiratory disease due to SARS-CoV-2.

Detailed Description: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 49

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
anti-CD14 + SOC	anti-CD14	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.
Placebo + SOC	Placebo	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.
anti-CD14 + SOC	remdesivir	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.
Placebo + SOC	remdesivir	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.

Primary Outcome Measures

Name	Time	Method
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.	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

Secondary Outcome Measures

Name	Time	Method
All-Cause Mortality Through Day 28.	Within the 28 day period following baseline.	Mortality due to all causes during the observation period.
Days Alive and Free of Any Episodes of Acute Respiratory Failure Through Day 28	Within the 28 day period following baseline.	Episodes of acute respiratory failure are defined as by need for the following oxygen delivery resources: 1. High-flow nasal cannula (flow rates ≥30L/min with FiO2 ≥0.4) 2. Noninvasive positive-pressure ventilation through nasal or face mask, or nasal plugs 3. Endotracheal intubation and mechanical 4. Extracorporeal membrane oxygenation
Change in Ordinal Scale From Baseline to Day 28.	Within the 28 day period following baseline.	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: 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.
Ordinal Scale Value on Day 14.	Day 14 following 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: 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.
Adverse Events (AEs)	Within the 28 day period following baseline.	Number of Grade 3 and 4 clinical and/or laboratory adverse events
Change in the Ordinal Scale From Baseline to Day 14	Within the 14 day period following baseline.	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: 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.
Percentage of Participants Alive and Free of Any Episode of Acute Respiratory Failure Through Day 28	Within the 28 day period following baseline.	Episodes of acute respiratory failure are defined as by need for the following oxygen delivery resources: 1. High-flow nasal cannula (flow rates ≥30L/min with FiO2 ≥0.4) 2. Noninvasive positive-pressure ventilation through nasal or face mask, or nasal plugs 3. Endotracheal intubation and mechanical ventilation 4. Extracorporeal membrane oxygenation
Days Alive and Free of Invasive Mechanical Ventilation Through Day 28	Within the 28 day period following baseline.	Endotracheal intubation and mechanical ventilation.
Percentage of Participants Alive and Free of Invasive Mechanical Ventilation Through Day 28	Within the 28 day period following baseline.	Endotracheal intubation and mechanical ventilation.
Percentage of Participants Alive and Discharged From the Hospital Through Day 28	Within the 28 day period following baseline.	Participants must be alive and discharged from hospital.
Percent of Participants Who Begin Corticosteroid Therapy for Worsening COVID-19 Illness After Randomization	Within the 28 day period following baseline.	Initiation of corticosteroid therapy.
Serious Adverse Events (SAEs)	Within the 28 day period following baseline.	Number of serious adverse events
All-Cause Mortality Through Day 60.	Within the 60 day period following baseline.	Mortality due to all causes during the observation period.

Trial Locations

Locations (5): Sarasota Memorial Health Care System
🇺🇸
Sarasota, Florida, United States
Virginia Mason Medical Center
🇺🇸
Seattle, Washington, United States
Harborview Medical Center
🇺🇸
Seattle, Washington, United States
Swedish Medical Center
🇺🇸
Seattle, Washington, United States
University of Washington Medical Center-Montlake
🇺🇸
Seattle, Washington, United States