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

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ClinicalTrials.gov Identifier: NCT04391309
Recruitment Status : Recruiting
First Posted : May 18, 2020
Last Update Posted : June 3, 2021
Sponsor:
Collaborators:
University of Washington
Implicit Bioscience
Vanderbilt University Medical Center
PPD
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

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.

Condition or disease Intervention/treatment Phase
Coronavirus Disease 2019 (COVID-19) Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Biological: anti-CD14 Other: Placebo Drug: remdesivir Phase 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, Double-Blind, Placebo-Controlled
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Placebo consists of identical-appearing diluent
Primary Purpose: Treatment
Official Title: Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of the Effect of Anti-CD14 Treatment in Hospitalized Patients With COVID-19
Actual Study Start Date : April 12, 2021
Estimated Primary Completion Date : November 2021
Estimated Study Completion Date : February 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: anti-CD14 + SOC

Anti-CD14: 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 Name: Veklury®

Placebo Comparator: Placebo + SOC

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 Name: 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 Name: Veklury®




Primary Outcome Measures :
  1. Time to Clinical Recovery [ Time Frame: Day 0-28 ]

    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


Secondary Outcome Measures :
  1. Days Alive and Free of Any Episodes of Acute Respiratory Failure through Day 28 [ Time Frame: Days 0-28 ]

    Defined by need for any of 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 ventilation
    4. Extracorporeal membrane oxygenation

  2. Mean Change in the Ordinal Scale (Range 1 [Best] to 8 [Worst]) [ Time Frame: Days 0-14 and Days 0-28 ]
    Ordinal scale as defined above

  3. Ordinal Scale Value on Day 14 (Range 1 [Best] to 8 [Worst]) [ Time Frame: Day 14 ]
    Ordinal scale as defined above

  4. All-Cause Mortality through Days 28 and 60 [ Time Frame: Days 0-28 and Days 0-60 ]
    Mortality due to all causes during the observation period

  5. Proportion of Participants Alive and Free of Any Episode of Acute Respiratory Failure through Day 28 [ Time Frame: Days 0-28 ]

    Defined by need for any of the following oxygen delivery resources:

    1. High-flow nasal cannula (flow rates ≥30L/min with FiO2 ≥0.4)
    2. Noninvasive positive-pressure ventilation
    3. Endotracheal intubation and mechanical ventilation
    4. Extracorporeal membrane oxygenation

  6. Days Alive and Free of Invasive Mechanical Ventilation through Day 28 [ Time Frame: Days 0-28 ]
    Invasive mechanical ventilation defined above

  7. Proportion of Participants Alive and Free of Invasive Mechanical Ventilation through Day 28 [ Time Frame: Days 0-28 ]
    Invasive mechanical ventilation defined above

  8. Proportion of Participants Alive and Discharged from the Hospital through Day 28 [ Time Frame: Days 0-28 ]
    Discharged from hospital and alive

  9. Proportion of Participants who Begin Corticosteroid Therapy for Worsening COVID-19 Illness after Randomization [ Time Frame: Days 0-28 ]
    Initiation of systemic corticosteroid therapy

  10. Serious Adverse Events (SAEs) [ Time Frame: Days 0-28 ]
    Cumulative incidence of serious adverse events

  11. Adverse Events (AEs) [ Time Frame: Days 0-28 ]
    Cumulative incidence of Grade 3 and 4 clinical and/or laboratory adverse events

  12. Safety of IC14 as Measured by Change from Baseline in ALT and AST Liver Function Tests [ Time Frame: Days 0-28 ]

    Serum liver function tests, hepatic/metabolic biomarkers:

    • serum alanine aminotransferase (ALT/SGPT), and
    • serum aspartate aminotransferase (AST/SGOT)

    Unit of Measure: U/L


  13. Safety of IC14 as Measured by Change from Baseline in Liver Function Measured by Total Bilirubin [ Time Frame: Days 0-28 ]

    Serum total bilirubin, an hepatic/metabolic biomarker.

    Unit of Measure: mg/dL


  14. Safety of IC14 as Measured by Change from Baseline in Serum Creatinine [ Time Frame: Days 0-28 ]

    Evaluation of kidney function by serum creatinine laboratory test.

    Unit of Measure mg/dL


  15. Safety of IC14 as Measured by Change from Baseline in Hemoglobin [ Time Frame: Days 0-28 ]
    A hematologic measure (g/dL).

  16. Safety of IC14 as Measured by Change from Baseline in White Blood Cell Count [ Time Frame: Days 0-28 ]

    Hematologic measure: White Blood Cell (WBC) count.

    Unit of Measure: 1.0x10^3/mcL.


  17. Safety of IC14 as Measured by Change from Baseline in Differential White Blood Count [ Time Frame: Days 0-28 ]

    Hematology parameters: differential white blood cells (WBC) count (neutrophils, lymphocytes, monocytes, eosinophil's, and basophils).

    Unit of measure (absolute): K/mcL


  18. Safety of IC14 as Measured by Change from Baseline in Platelet Count [ Time Frame: Days 0-28 ]

    Hematologic/coagulation parameter.

    Unit of Measure: 1.0x10^3/mcL


  19. Safety of IC14 as Measured by Change from Baseline in Prothrombin Time [ Time Frame: Days 0-28 ]
    Coagulation function. Unit of measure: seconds


Other Outcome Measures:
  1. EXPLORATORY: Change in Sequential Organ Failure Assessment (SOFA) Score from Baseline to Days 7, 14, 21 and 28 [ Time Frame: Days 0-7, Days 0-14, Days 0-21, and Days 0-28 ]
    Sequential Organ Failure Assessment score (range 0 [best] to 24 [worst])

  2. EXPLORATORY: Worst SOFA Score from Baseline to Day 28 [ Time Frame: Days 0-28 ]
    Sequential Organ Failure Assessment score (range 0 [best] to 24 [worst])

  3. EXPLORATORY: Time from Baseline to Improvement in One Category Using an Ordinal Scale through Day 28 [ Time Frame: Days 0-28 ]
    Ordinal scale defined above (range 1 [best] to 8 [worst])

  4. EXPLORATORY: Time from Baseline to Improvement in Two Categories Using an Ordinal Scale through Day 28 [ Time Frame: Days 0-28 ]
    Ordinal scale defined above (range 1 [best] to 8 [worst])

  5. EXPLORATORY: Proportion of Participants with Negative Nasal Swabs for SARS CoV2 Virus [ Time Frame: Up to Day 14 ]
    Nasal swab culture for SARS COV2

  6. EXPLORATORY: Change from Baseline in Pro-Inflammatory Cytokines [ Time Frame: Days 0, 4, 7, 14 and 21 ]

    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


  7. EXPLORATORY: Change from Baseline in C-Reactive Protein (CRP) [ Time Frame: Days 0, 4, 7, 14 and 21 ]

    An inflammatory biomarker.

    Unit of Measure: mg/L


  8. EXPLORATORY: Change from Baseline in Ferritin [ Time Frame: Days 0, 4, 7, 14 and 21 ]

    An inflammatory biomarker.

    Unit of Measure: mcg/L


  9. EXPLORATORY: Change from Baseline in Lactate Dehydrogenase (LDH) [ Time Frame: Days 0, 4, 7, 14 and 21 ]

    An inflammatory biomarker.

    Unit of Measure:U/L




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04391309


Locations
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United States, California
Harbor - UCLA Medical Center Not yet recruiting
Torrance, California, United States, 90502
Principal Investigator: Dong Chang, MD         
United States, Florida
University of Miami Medical Center Not yet recruiting
Miami Beach, Florida, United States, 33136
Principal Investigator: Gregory E. Holt, MD, PhD         
Sarasota Memorial Health Care System Recruiting
Sarasota, Florida, United States, 34236
Contact: Tamela Fonseca    941-228-1752    Tamela-Fonseca@smh.com   
Principal Investigator: Kirk G. Voelker, MD         
United States, Georgia
Emory University Medical Center Not yet recruiting
Atlanta, Georgia, United States, 30322
Contact: Alex Hall    404-778-1585    alex.hall@emory.edu   
Principal Investigator: Carmen Polito, MD, MSc         
United States, Louisiana
Ochsner Health Recruiting
New Orleans, Louisiana, United States, 70121
Contact: Laura Raymond    504-842-6726    Laraymond@ochsner.org   
Principal Investigator: Julia B. Garcia-Diaz, MD         
United States, Maryland
University of Maryland Medical Center Not yet recruiting
Baltimore, Maryland, United States, 21201
Principal Investigator: Carl B. Shanholtz, MD         
United States, Massachusetts
Baystate Medical Center Not yet recruiting
Springfield, Massachusetts, United States, 01199
Contact: Alison Griffin    413-794-0903    Alison.Griffin@baystatehealth.org   
Principal Investigator: Jay S. Steingrub, MD         
United States, Ohio
Cleveland Clinic Not yet recruiting
Cleveland, Ohio, United States, 44195
Principal Investigator: Abhijit Duggal, MD         
United States, Pennsylvania
Thomas Jefferson University Hospital Not yet recruiting
Philadelphia, Pennsylvania, United States, 19107
Principal Investigator: Jesse Roman, MD         
United States, Washington
Virginia Mason Medical Center Recruiting
Seattle, Washington, United States, 98101
Contact: Kate Duran    206-287-6268    kate.duran@virginiamason.org   
Principal Investigator: Uma Malhotra, MD         
Harborview Medical Center Recruiting
Seattle, Washington, United States, 98104
Contact: Elizabeth Barnes    206-295-0640    barneeli@uw.edu   
Principal Investigator: Mark M. Wurfel, MD, PhD         
Swedish Medical Center Not yet recruiting
Seattle, Washington, United States, 98109
Principal Investigator: Shane O'Mahony, MD         
University of Washington Medical Center-Montlake Recruiting
Seattle, Washington, United States, 98195
Contact: Carolyn Brager    206-543-4287    bragerc@uw.edu   
Principal Investigator: Eric D. Morrell, MD         
University of Washington Medical Center Not yet recruiting
Seattle, Washington, United States, 98195
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
University of Washington
Implicit Bioscience
Vanderbilt University Medical Center
PPD
Investigators
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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
Additional Information:
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT04391309    
Other Study ID Numbers: DAIT COVID-19-003
NIAID CRMS ID#: 38756 ( Other Identifier: DAIT NIAID )
UM1AI109565 ( U.S. NIH Grant/Contract )
First Posted: May 18, 2020    Key Record Dates
Last Update Posted: June 3, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
anti-CD14 (anti-CD14 chimeric monoclonal antibody)
randomized double-blind placebo-controlled clinical trial
hospitalized patients
Additional relevant MeSH terms:
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Coronavirus Infections
Severe Acute Respiratory Syndrome
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs