Clinical trial NCT04391309: COVID-19 and Anti-CD14 Treatment Trial
Official title: Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of the Effect of Anti-CD14 Treatment in Hospitalized Patients With COVID-19
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Coronavirus Disease 2019 (COVID-19)
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Keywords: anti-CD14 (anti-CD14 chimeric monoclonal antibody)
randomized double-blind placebo-controlled clinical trial
hospitalized patients
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: University of Washington
name: Implicit Bioscience
name: Vanderbilt University Medical Center
name: PPD Development, LP
First posted: 2020-05-18
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, Double-Blind, Placebo-Controlled
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: Within the 28 day period following baseline
Secondary outcomes:
measure: Days Alive and Free of Any Episodes of Acute Respiratory Failure Through Day 28
timeFrame: Within the 28 day period following baseline.
measure: Change in the Ordinal Scale From Baseline to Day 14
timeFrame: Within the 14 day period following baseline.
measure: Change in Ordinal Scale From Baseline to Day 28.
timeFrame: Within the 28 day period following baseline.
measure: Ordinal Scale Value on Day 14.
timeFrame: Day 14 following baseline.
measure: All-Cause Mortality Through Day 28.
timeFrame: Within the 28 day period following baseline.
measure: All-Cause Mortality Through Day 60.
timeFrame: Within the 60 day period following baseline.
measure: Percentage of Participants Alive and Free of Any Episode of Acute Respiratory Failure Through Day 28
timeFrame: Within the 28 day period following baseline.
measure: Days Alive and Free of Invasive Mechanical Ventilation Through Day 28
timeFrame: Within the 28 day period following baseline.
measure: Percentage of Participants Alive and Free of Invasive Mechanical Ventilation Through Day 28
timeFrame: Within the 28 day period following baseline.
measure: Percentage of Participants Alive and Discharged From the Hospital Through Day 28
timeFrame: Within the 28 day period following baseline.
measure: Percent of Participants Who Begin Corticosteroid Therapy for Worsening COVID-19 Illness After Randomization
timeFrame: Within the 28 day period following baseline.
measure: Serious Adverse Events (SAEs)
timeFrame: Within the 28 day period following baseline.
measure: Adverse Events (AEs)
timeFrame: Within the 28 day period following baseline.
Other outcomes:
Locations:
city: Sarasota
country: United States
facility: Sarasota Memorial Health Care System
state: Florida
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center-Montlake
state: Washington
Study officials:
affiliation: University of Washington: Division of Pulmonary, Critical Care and Sleep Medicine
name: Mark M. Wurfel, MD, PhD
role: STUDY_CHAIR
affiliation: University of Washington: Division of Pulmonary, Critical Care and Sleep Medicine
name: Thomas R. Martin, MD
role: STUDY_CHAIR
References: