COVID-19 and Anti-CD14 Treatment Trial

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

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.

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.

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.