CaTT: COVID-19 and Anti-CD14 Treatment Trial
Study Details
Study Description
Brief Summary
This study aims to address the following objectives:
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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.
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To determine the efficacy of IC14 in reducing the severity of respiratory disease in patients hospitalized with respiratory disease due to SARS-CoV-2.
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To determine the safety of IC14 in patients hospitalized with respiratory disease due to SARS-CoV-2.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
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.
Study Design
Arms and Interventions
| 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:
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:
|
| 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 Names:
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:
|
Outcome Measures
Primary Outcome Measures
- Time to Clinical Recovery [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: 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
Secondary Outcome Measures
- Days Alive and Free of Any Episodes of Acute Respiratory Failure through Day 28 [Days 0-28]
Defined by need for any of 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
- Mean Change in the Ordinal Scale (Range 1 [Best] to 8 [Worst]) [Days 0-14 and Days 0-28]
Ordinal scale as defined above
- Ordinal Scale Value on Day 14 (Range 1 [Best] to 8 [Worst]) [Day 14]
Ordinal scale as defined above
- All-Cause Mortality through Days 28 and 60 [Days 0-28 and Days 0-60]
Mortality due to all causes during the observation period
- Proportion of Participants Alive and Free of Any Episode of Acute Respiratory Failure through Day 28 [Days 0-28]
Defined by need for any of the following oxygen delivery resources: High-flow nasal cannula (flow rates ≥30L/min with FiO2 ≥0.4) Noninvasive positive-pressure ventilation Endotracheal intubation and mechanical ventilation Extracorporeal membrane oxygenation
- Days Alive and Free of Invasive Mechanical Ventilation through Day 28 [Days 0-28]
Invasive mechanical ventilation defined above
- Proportion of Participants Alive and Free of Invasive Mechanical Ventilation through Day 28 [Days 0-28]
Invasive mechanical ventilation defined above
- Proportion of Participants Alive and Discharged from the Hospital through Day 28 [Days 0-28]
Discharged from hospital and alive
- Proportion of Participants who Begin Corticosteroid Therapy for Worsening COVID-19 Illness after Randomization [Days 0-28]
Initiation of systemic corticosteroid therapy
- Serious Adverse Events (SAEs) [Days 0-28]
Cumulative incidence of serious adverse events
- Adverse Events (AEs) [Days 0-28]
Cumulative incidence of Grade 3 and 4 clinical and/or laboratory adverse events
- Safety of IC14 as Measured by Change from Baseline in ALT and AST Liver Function Tests [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
- Safety of IC14 as Measured by Change from Baseline in Liver Function Measured by Total Bilirubin [Days 0-28]
Serum total bilirubin, an hepatic/metabolic biomarker. Unit of Measure: mg/dL
- Safety of IC14 as Measured by Change from Baseline in Serum Creatinine [Days 0-28]
Evaluation of kidney function by serum creatinine laboratory test. Unit of Measure mg/dL
- Safety of IC14 as Measured by Change from Baseline in Hemoglobin [Days 0-28]
A hematologic measure (g/dL).
- Safety of IC14 as Measured by Change from Baseline in White Blood Cell Count [Days 0-28]
Hematologic measure: White Blood Cell (WBC) count. Unit of Measure: 1.0x10^3/mcL.
- Safety of IC14 as Measured by Change from Baseline in Differential White Blood Count [Days 0-28]
Hematology parameters: differential white blood cells (WBC) count (neutrophils, lymphocytes, monocytes, eosinophil's, and basophils). Unit of measure (absolute): K/mcL
- Safety of IC14 as Measured by Change from Baseline in Platelet Count [Days 0-28]
Hematologic/coagulation parameter. Unit of Measure: 1.0x10^3/mcL
- Safety of IC14 as Measured by Change from Baseline in Prothrombin Time [Days 0-28]
Coagulation function. Unit of measure: seconds
Other Outcome Measures
- EXPLORATORY: Change in Sequential Organ Failure Assessment (SOFA) Score from Baseline to Days 7, 14, 21 and 28 [Days 0-7, Days 0-14, Days 0-21, and Days 0-28]
Sequential Organ Failure Assessment score (range 0 [best] to 24 [worst])
- EXPLORATORY: Worst SOFA Score from Baseline to Day 28 [Days 0-28]
Sequential Organ Failure Assessment score (range 0 [best] to 24 [worst])
- EXPLORATORY: Time from Baseline to Improvement in One Category Using an Ordinal Scale through Day 28 [Days 0-28]
Ordinal scale defined above (range 1 [best] to 8 [worst])
- EXPLORATORY: Time from Baseline to Improvement in Two Categories Using an Ordinal Scale through Day 28 [Days 0-28]
Ordinal scale defined above (range 1 [best] to 8 [worst])
- EXPLORATORY: Proportion of Participants with Negative Nasal Swabs for SARS CoV2 Virus [Up to Day 14]
Nasal swab culture for SARS COV2
- EXPLORATORY: Change from Baseline in Pro-Inflammatory Cytokines [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
- EXPLORATORY: Change from Baseline in C-Reactive Protein (CRP) [Days 0, 4, 7, 14 and 21]
An inflammatory biomarker. Unit of Measure: mg/L
- EXPLORATORY: Change from Baseline in Ferritin [Days 0, 4, 7, 14 and 21]
An inflammatory biomarker. Unit of Measure: mcg/L
- EXPLORATORY: Change from Baseline in Lactate Dehydrogenase (LDH) [Days 0, 4, 7, 14 and 21]
An inflammatory biomarker. Unit of Measure:U/L
Eligibility Criteria
Criteria
Inclusion Criteria:
Patients included in the study must meet all the following criteria:
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Patient or legally authorized representative able to provide informed consent
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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
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Radiologic findings compatible with diagnosis of SARS-CoV-2 pulmonary infection
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Hypoxemia as defined by any of the following:
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SpO2 ≤94% on room air, or
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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
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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:
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Receiving non-invasive positive-pressure ventilation through nasal mask, face mask, or nasal plugs
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Receiving invasive mechanical ventilation
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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)
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Anticipated survival <48 hours
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Underlying malignancy, or other condition, with estimated life expectancy of less than two months
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Significant pre-existing organ dysfunction prior to randomization
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Lung: Currently receiving home oxygen therapy as documented in medical record
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Heart: Pre-existing congestive heart failure defined as an ejection fraction <20% as documented in the medical record
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Renal: End-stage renal disease requiring renal replacement therapy or eGFR <30 mL/min
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Liver: Severe chronic liver disease defined as Child-Pugh Class C or AST or ALT
5x upper limit of normal
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Hematologic: Baseline platelet count <50,000/mm^3
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Presence of co-existing infection, including, but not limited to:
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HIV infection not virally suppressed and with pre-hospitalization CD4 counts ≤ 500 cell/mm^3
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Active tuberculosis or a history of inadequately treated tuberculosis
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Active hepatitis B or hepatitis C viral infection
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Ongoing immunosuppression
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Solid organ transplant recipient
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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
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Oncolytic drug therapy within the past 14 days
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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
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Current treatment with an anti-viral medication for COVID-19 (e.g. hydroxychloroquine, lopinavir/ritonavir), other than remdesivir
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Current enrollment in an interventional trial for COVID-19
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History of hypersensitivity or idiosyncratic reaction to IC14
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Women who are currently breastfeeding
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Received a live-attenuated vaccine within 30 days prior to enrollment
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Received five or more doses of remdesivir, including the loading dose, outside of the study as treatment for COVID-19, or
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Any condition that in the opinion of the treating physician will increase the risk for the participant.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Harbor - UCLA Medical Center | Torrance | California | United States | 90502 |
| 2 | University of Miami Medical Center | Miami Beach | Florida | United States | 33136 |
| 3 | Sarasota Memorial Health Care System | Sarasota | Florida | United States | 34236 |
| 4 | Emory University Medical Center | Atlanta | Georgia | United States | 30322 |
| 5 | Ochsner Health | New Orleans | Louisiana | United States | 70121 |
| 6 | University of Maryland Medical Center | Baltimore | Maryland | United States | 21201 |
| 7 | Baystate Medical Center | Springfield | Massachusetts | United States | 01199 |
| 8 | Cleveland Clinic | Cleveland | Ohio | United States | 44195 |
| 9 | Thomas Jefferson University Hospital | Philadelphia | Pennsylvania | United States | 19107 |
| 10 | Virginia Mason Medical Center | Seattle | Washington | United States | 98101 |
| 11 | Harborview Medical Center | Seattle | Washington | United States | 98104 |
| 12 | Swedish Medical Center | Seattle | Washington | United States | 98122 |
| 13 | University of Washington Medical Center-Montlake | Seattle | Washington | United States | 98195 |
| 14 | University of Washington Medical Center | 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
- 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
Study Documents (Full-Text)
None provided.More Information
Additional Information:
- National Institutes of Health News Release Describing Study
- National Institute of Allergy and Infectious Diseases (NIAID)
- NIAID Division of Allergy, Immunology, and Transplantation (DAIT)
- Centers for Disease Control and Prevention -COVID-19 resources
Publications
None provided.- DAIT COVID-19-003
- NIAID CRMS ID#: 38756
- UM1AI109565