Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Randomized, Double-Blind, Placebo-Controlled
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Placebo consists of identical-appearing diluent

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
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.
  • Biological: anti-CD14
    4 mg/kg on Day 1, 2 mg/kg on Days 2-4 administered intravenously (IV)
    Other names:
    • monoclonal antibody to CD14
    • IC14
  • Drug: remdesivir
    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.
    Other names:
    • Veklury®
Placebo Comparator
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.
  • Other: Placebo
    Placebo administered intravenously on Days 1-4
    Other names:
    • Placebo for anti-CD14
  • Drug: remdesivir
    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.
    Other names:
    • Veklury®

Recruiting Locations

More Details

NCT ID
NCT04391309
Status
Terminated
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.