COVID-19 and Anti-CD14 Treatment Trial (CaTT)

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.

Study Overview

• Status: Terminated
• Conditions: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2); Coronavirus Disease 2019 (COVID-19)
• Intervention / Treatment: Biological: anti-CD14; Drug: remdesivir; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Sarasota, Florida, United States, 34236
      • Sarasota Memorial Health Care System
  • Washington
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center-Montlake

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	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®; Other: Placebo; Placebo administered intravenously on Days 1-4; Other Names: Placebo for anti-CD14

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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: Not hospitalized, no limitations on activities; Not hospitalized, limitation on activities and/or requiring home oxygen; Hospitalized, not requiring supplemental oxygen-no longer requires ongoing medical care; Hospitalized, not requiring supplemental oxygen-requiring ongoing medical care (COVID-19-related or otherwise); Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high-flow oxygen devices; Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Death	Within the 28 day period following baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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: High-flow nasal cannula (flow rates ≥30L/min with FiO2 ≥0.4); Noninvasive positive-pressure ventilation through nasal or face mask, or nasal plugs; Endotracheal intubation and mechanical; Extracorporeal membrane oxygenation	Within the 28 day period following baseline.
Change in the Ordinal Scale From Baseline to Day 14	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: Not hospitalized, no limitations on activities.; Not hospitalized, limitation on activities and/or requiring home oxygen.; Hospitalized, not requiring supplemental oxygen; no longer requires ongoing medical care.; Hospitalized, not requiring supplemental oxygen; requiring ongoing medical care (COVID-19-related or otherwise).; Hospitalized, requiring supplemental oxygen.; Hospitalized, on non-invasive ventilation or high-flow oxygen devices.; Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO).; Death.	Within the 14 day period following baseline.
Change in Ordinal Scale From Baseline to Day 28.	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: Not hospitalized, no limitations on activities.; Not hospitalized, limitation on activities and/or requiring home oxygen.; Hospitalized, not requiring supplemental oxygen; no longer requires ongoing medical care.; Hospitalized, not requiring supplemental oxygen; requiring ongoing medical care (COVID-19-related or otherwise).; Hospitalized, requiring supplemental oxygen.; Hospitalized, on non-invasive ventilation or high-flow oxygen devices.; Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO).; Death.	Within the 28 day period following baseline.
Ordinal Scale Value on Day 14.	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: Not hospitalized, no limitations on activities.; Not hospitalized, limitation on activities and/or requiring home oxygen.; Hospitalized, not requiring supplemental oxygen; no longer requires ongoing medical care.; Hospitalized, not requiring supplemental oxygen; requiring ongoing medical care (COVID-19-related or otherwise).; Hospitalized, requiring supplemental oxygen.; Hospitalized, on non-invasive ventilation or high-flow oxygen devices.; Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO).; Death.	Day 14 following baseline.
All-Cause Mortality Through Day 28.	Mortality due to all causes during the observation period.	Within the 28 day period following baseline.
All-Cause Mortality Through Day 60.	Mortality due to all causes during the observation period.	Within the 60 day period following baseline.
Percentage of Participants Alive and Free of Any Episode of Acute Respiratory Failure Through Day 28	Episodes of acute respiratory failure are defined as by need for the following oxygen delivery resources: High-flow nasal cannula (flow rates ≥30L/min with FiO2 ≥0.4); Noninvasive positive-pressure ventilation through nasal or face mask, or nasal plugs; Endotracheal intubation and mechanical ventilation; Extracorporeal membrane oxygenation	Within the 28 day period following baseline.
Days Alive and Free of Invasive Mechanical Ventilation Through Day 28	Endotracheal intubation and mechanical ventilation.	Within the 28 day period following baseline.
Percentage of Participants Alive and Free of Invasive Mechanical Ventilation Through Day 28	Endotracheal intubation and mechanical ventilation.	Within the 28 day period following baseline.
Percentage of Participants Alive and Discharged From the Hospital Through Day 28	Participants must be alive and discharged from hospital.	Within the 28 day period following baseline.
Percent of Participants Who Begin Corticosteroid Therapy for Worsening COVID-19 Illness After Randomization	Initiation of corticosteroid therapy.	Within the 28 day period following baseline.
Serious Adverse Events (SAEs)	Number of serious adverse events	Within the 28 day period following baseline.
Adverse Events (AEs)	Number of Grade 3 and 4 clinical and/or laboratory adverse events	Within the 28 day period following baseline.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
EXPLORATORY: Change in Sequential Organ Failure Assessment (SOFA) Score from Baseline to Days 7, 14, 21 and 28	Sequential Organ Failure Assessment score (range 0 [best] to 24 [worst])	Days 0-7, Days 0-14, Days 0-21, and Days 0-28
EXPLORATORY: Worst SOFA Score from Baseline to Day 28	Sequential Organ Failure Assessment score (range 0 [best] to 24 [worst])	Days 0-28
EXPLORATORY: Time from Baseline to Improvement in One Category Using an Ordinal Scale through Day 28	Ordinal scale defined above (range 1 [best] to 8 [worst])	Days 0-28
EXPLORATORY: Time from Baseline to Improvement in Two Categories Using an Ordinal Scale through Day 28	Ordinal scale defined above (range 1 [best] to 8 [worst])	Days 0-28
EXPLORATORY: Proportion of Participants with Negative Nasal Swabs for SARS CoV2 Virus	Nasal swab culture for SARS COV2	Up to Day 14
EXPLORATORY: Change from Baseline in Pro-Inflammatory Cytokines	Pro-inflammatory cytokines are involved in the up-regulation of inflammatory reactions. Exploratory blood serum samples evaluated by ELISA assay, will include the following: Tumor Necrosis Factor-alpha (TNF-α),; Interleukin-1 beta (IL-1B),; Interleukin-6 (IL-6),; Interleukin-8 (IL-8),; Interleukin-10 (IL-10), and; granulocyte-macrophage colony-stimulating factor (GM-CSF) Unit of Measure: pg/mL	Days 0, 4, 7, 14 and 21
EXPLORATORY: Change from Baseline in C-Reactive Protein (CRP)	An inflammatory biomarker. Unit of Measure: mg/L	Days 0, 4, 7, 14 and 21
EXPLORATORY: Change from Baseline in Ferritin	An inflammatory biomarker. Unit of Measure: mcg/L	Days 0, 4, 7, 14 and 21
EXPLORATORY: Change from Baseline in Lactate Dehydrogenase (LDH)	An inflammatory biomarker. Unit of Measure:U/L	Days 0, 4, 7, 14 and 21

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: PPD; University of Washington; Vanderbilt University Medical Center; Implicit Bioscience
• Investigators: Study Chair: Mark M. Wurfel, MD, PhD, University of Washington: Division of Pulmonary, Critical Care and Sleep Medicine; Study Chair: Thomas R. Martin, MD, University of Washington: Division of Pulmonary, Critical Care and Sleep Medicine

Publications and helpful links

Helpful Links

• National Institute of Allergy and Infectious Diseases (NIAID)
• National Institutes of Health News Release Describing Study
• NIAID Division of Allergy, Immunology, and Transplantation (DAIT)
• Centers for Disease Control and Prevention -COVID-19 resources

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2021
• Primary Completion (Actual): February 4, 2022
• Study Completion (Actual): February 4, 2022

Study Registration Dates

• First Submitted: May 14, 2020
• First Submitted That Met QC Criteria: May 14, 2020
• First Posted (Actual): May 18, 2020

Study Record Updates

• Last Update Posted (Actual): June 26, 2023
• Last Update Submitted That Met QC Criteria: June 20, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: anti-CD14 (anti-CD14 chimeric monoclonal antibody); randomized double-blind placebo-controlled clinical trial; hospitalized patients
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Severe Acute Respiratory Syndrome; COVID-19; Coronavirus Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Remdesivir
• Other Study ID Numbers: DAIT COVID-19-003; UM1AI109565 (U.S. NIH Grant/Contract); NIAID CRMS ID#: 38756 (Other Identifier: DAIT NIAID)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No