COVID-19 and Anti-CD14 Treatment Trial

Phase 2TerminatedNCT04391309

National Institute of Allergy and Infectious Diseases (NIAID)49 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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: 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

Time frame: Within the 28 day period following baseline

Secondary Outcomes

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: 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