Coronavirus Disease 2019 (COVID-19), Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Conditions
Keywords
anti-CD14 (anti-CD14 chimeric monoclonal antibody), randomized double-blind placebo-controlled clinical trial, hospitalized patients
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.
Interventions
BIOLOGICALanti-CD14
4 mg/kg on Day 1, 2 mg/kg on Days 2-4 administered intravenously (IV)
OTHERPlacebo
Placebo administered intravenously on Days 1-4
DRUGremdesivir
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.
Sponsors
University of Washington
Implicit Bioscience
Vanderbilt University Medical Center
PPD Development, LP
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Placebo consists of identical-appearing diluent
Intervention model description
Randomized, Double-Blind, Placebo-Controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Within the 28 day period following baseline | 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
| Measure | Time frame | Description |
|---|---|---|
| Change in the Ordinal Scale From Baseline to Day 14 | Within the 14 day period following baseline. | 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: 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. |
| Change in Ordinal Scale From Baseline to Day 28. | Within the 28 day period following baseline. | 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: 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. |
| Ordinal Scale Value on Day 14. | Day 14 following 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: 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. |
| All-Cause Mortality Through Day 28. | Within the 28 day period following baseline. | Mortality due to all causes during the observation period. |
| All-Cause Mortality Through Day 60. | Within the 60 day period following baseline. | Mortality due to all causes during the observation period. |
| Percentage of Participants Alive and Free of Any Episode of Acute Respiratory Failure Through Day 28 | Within the 28 day period following baseline. | 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 ventilation 4. Extracorporeal membrane oxygenation |
| Days Alive and Free of Any Episodes of Acute Respiratory Failure Through Day 28 | Within the 28 day period following baseline. | 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 |
| Percentage of Participants Alive and Free of Invasive Mechanical Ventilation Through Day 28 | Within the 28 day period following baseline. | Endotracheal intubation and mechanical ventilation. |
| Percentage of Participants Alive and Discharged From the Hospital Through Day 28 | Within the 28 day period following baseline. | Participants must be alive and discharged from hospital. |
| Percent of Participants Who Begin Corticosteroid Therapy for Worsening COVID-19 Illness After Randomization | Within the 28 day period following baseline. | Initiation of corticosteroid therapy. |
| Serious Adverse Events (SAEs) | Within the 28 day period following baseline. | Number of serious adverse events |
| Adverse Events (AEs) | Within the 28 day period following baseline. | Number of Grade 3 and 4 clinical and/or laboratory adverse events |
| Days Alive and Free of Invasive Mechanical Ventilation Through Day 28 | Within the 28 day period following baseline. | Endotracheal intubation and mechanical ventilation. |
Countries
United States
Participant flow
Recruitment details
49 participants were enrolled across 5 US sites from April 2021 to January 2022. Of these enrolled, 41 participants were randomized and 40 initiated study treatment. 8 enrolled participants were not randomized because they did not meet eligibility criteria, and one randomized participant did not initiate study treatment because they withdrew their consent.
Pre-assignment details
8 enrolled participants were not randomized because they did not meet eligibility criteria.
Participants by arm
| Arm | Count |
|---|---|
| IC14 Subjects received IC14 4 mg/kg intravenously on Day 1, followed by IC14 2 mg/kg/day intravenously on Days 2-4 (totaling 4 consecutive days). Subjects also received remdesivir 200 mg intravenously on Day 1, followed by 100 mg intravenously daily on Days 2-5 (totaling 5 consecutive days). | 20 |
| Placebo Subjects received 0.9% w/v Sodium Chloride in a matching bag and volume administered intravenously daily on Days 1-4 (totaling 4 consecutive days). Subjects also received remdesivir 200 mg intravenously on Day 1, followed by 100 mg intravenously daily on Days 2-5 (totaling 5 consecutive days). | 20 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 1 |
| Overall Study | Lost to Follow-up | 3 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Placebo | IC14 | Total |
|---|---|---|---|
| Age, Continuous | 47.1 years STANDARD_DEVIATION 13.6 | 54.5 years STANDARD_DEVIATION 14.7 | 50.85 years STANDARD_DEVIATION 14.46 |
| Assessment of Clinical Status According to Eight-Point Ordinal Scale 1 | 0 Participants | 0 Participants | 0 Participants |
| Assessment of Clinical Status According to Eight-Point Ordinal Scale 2 | 0 Participants | 0 Participants | 0 Participants |
| Assessment of Clinical Status According to Eight-Point Ordinal Scale 3 | 0 Participants | 0 Participants | 0 Participants |
| Assessment of Clinical Status According to Eight-Point Ordinal Scale 4 | 4 Participants | 1 Participants | 5 Participants |
| Assessment of Clinical Status According to Eight-Point Ordinal Scale 5 | 14 Participants | 18 Participants | 32 Participants |
| Assessment of Clinical Status According to Eight-Point Ordinal Scale 6 | 2 Participants | 1 Participants | 3 Participants |
| Assessment of Clinical Status According to Eight-Point Ordinal Scale 7 | 0 Participants | 0 Participants | 0 Participants |
| Assessment of Clinical Status According to Eight-Point Ordinal Scale 8 | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 15 Participants | 15 Participants | 30 Participants |
| Region of Enrollment United States | 20 participants | 20 participants | 40 participants |
| Sex: Female, Male Female | 7 Participants | 9 Participants | 16 Participants |
| Sex: Female, Male Male | 13 Participants | 11 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 20 | 1 / 20 |
| other Total, other adverse events | 16 / 20 | 13 / 20 |
| serious Total, serious adverse events | 4 / 20 | 1 / 20 |
Outcome results
Primary
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
Population: Modified Intent to Treat population (mITT), that included all participants who were randomized and treated with at least one dose of investigational product.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IC14 | 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. | 6 days |
| Placebo | 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. | 5 days |
p-value: 0.435Log Rank
Secondary
Adverse Events (AEs)
Number of Grade 3 and 4 clinical and/or laboratory adverse events
Time frame: Within the 28 day period following baseline.
Population: All participants who initiated study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IC14 | Adverse Events (AEs) | Severe (Grade 3) | 12 Adverse Events |
| IC14 | Adverse Events (AEs) | Life Threatening (Grade 4) | 1 Adverse Events |
| Placebo | Adverse Events (AEs) | Severe (Grade 3) | 10 Adverse Events |
| Placebo | Adverse Events (AEs) | Life Threatening (Grade 4) | 1 Adverse Events |
Secondary
All-Cause Mortality Through Day 28.
Mortality due to all causes during the observation period.
Time frame: Within the 28 day period following baseline.
Population: Modified Intent to Treat population (mITT), that included all participants who were randomized and treated with at least one dose of investigational product.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IC14 | All-Cause Mortality Through Day 28. | Died | 1 Participants |
| IC14 | All-Cause Mortality Through Day 28. | Alive | 19 Participants |
| Placebo | All-Cause Mortality Through Day 28. | Alive | 20 Participants |
| Placebo | All-Cause Mortality Through Day 28. | Died | 0 Participants |
Comparison: All categories included in the analysis.p-value: 1Fisher Exact
Secondary
All-Cause Mortality Through Day 60.
Mortality due to all causes during the observation period.
Time frame: Within the 60 day period following baseline.
Population: Modified Intent to Treat population (mITT), that included all participants who were randomized and treated with at least one dose of investigational product.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IC14 | All-Cause Mortality Through Day 60. | Alive | 19 Participants |
| IC14 | All-Cause Mortality Through Day 60. | Died | 1 Participants |
| Placebo | All-Cause Mortality Through Day 60. | Alive | 19 Participants |
| Placebo | All-Cause Mortality Through Day 60. | Died | 1 Participants |
Comparison: All categories included in the analysisp-value: 1Fisher Exact
Secondary
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: 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.
Population: Modified Intent to Treat population (mITT), that included all participants who were randomized and treated with at least one dose of investigational product, who additionally had data collected on Day 28.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IC14 | Change in Ordinal Scale From Baseline to Day 28. | -3.7 units on a scale | Standard Deviation 0.6 |
| Placebo | Change in Ordinal Scale From Baseline to Day 28. | -3.3 units on a scale | Standard Deviation 1.6 |
p-value: 0.895Wilcoxon (Mann-Whitney)
Secondary
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: 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 14 day period following baseline.
Population: Modified Intent to Treat population (mITT), that included all participants who were randomized and treated with at least one dose of investigational product, who additionally had data collected on Day 14.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IC14 | Change in the Ordinal Scale From Baseline to Day 14 | -3.1 units on a scale | Standard Deviation 1.6 |
| Placebo | Change in the Ordinal Scale From Baseline to Day 14 | -2.8 units on a scale | Standard Deviation 1.6 |
p-value: 0.391Wilcoxon (Mann-Whitney)
Secondary
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
Time frame: Within the 28 day period following baseline.
Population: Modified Intent to Treat population (mITT), that included all participants who were randomized and treated with at least one dose of investigational product.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IC14 | Days Alive and Free of Any Episodes of Acute Respiratory Failure Through Day 28 | 0 days | 1 Participants |
| IC14 | Days Alive and Free of Any Episodes of Acute Respiratory Failure Through Day 28 | 24 days | 1 Participants |
| IC14 | Days Alive and Free of Any Episodes of Acute Respiratory Failure Through Day 28 | 27 days | 0 Participants |
| IC14 | Days Alive and Free of Any Episodes of Acute Respiratory Failure Through Day 28 | 28 days | 18 Participants |
| Placebo | Days Alive and Free of Any Episodes of Acute Respiratory Failure Through Day 28 | 28 days | 18 Participants |
| Placebo | Days Alive and Free of Any Episodes of Acute Respiratory Failure Through Day 28 | 0 days | 1 Participants |
| Placebo | Days Alive and Free of Any Episodes of Acute Respiratory Failure Through Day 28 | 27 days | 1 Participants |
| Placebo | Days Alive and Free of Any Episodes of Acute Respiratory Failure Through Day 28 | 24 days | 0 Participants |
Comparison: All categories included in the analysisp-value: 1Fisher Exact
Secondary
Days Alive and Free of Invasive Mechanical Ventilation Through Day 28
Endotracheal intubation and mechanical ventilation.
Time frame: Within the 28 day period following baseline.
Population: Modified Intent to Treat population (mITT), that included all participants who were randomized and treated with at least one dose of investigational product.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IC14 | Days Alive and Free of Invasive Mechanical Ventilation Through Day 28 | 0 days | 1 Participants |
| IC14 | Days Alive and Free of Invasive Mechanical Ventilation Through Day 28 | 28 days | 19 Participants |
| Placebo | Days Alive and Free of Invasive Mechanical Ventilation Through Day 28 | 0 days | 1 Participants |
| Placebo | Days Alive and Free of Invasive Mechanical Ventilation Through Day 28 | 28 days | 19 Participants |
Comparison: All categories included in the analysis.p-value: 1Fisher Exact
Secondary
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: 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: Day 14 following baseline.
Population: Modified Intent to Treat population (mITT), that included all participants who were randomized and treated with at least one dose of investigational product, who additionally had data collected on Day 14.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IC14 | Ordinal Scale Value on Day 14. | 1.9 units on a scale | Standard Deviation 1.6 |
| Placebo | Ordinal Scale Value on Day 14. | 2.0 units on a scale | Standard Deviation 1.6 |
p-value: 0.702Wilcoxon (Mann-Whitney)
Secondary
Percentage of Participants Alive and Discharged From the Hospital Through Day 28
Participants must be alive and discharged from hospital.
Time frame: Within the 28 day period following baseline.
Population: Modified Intent to Treat population (mITT), that included all participants who were randomized and treated with at least one dose of investigational product.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IC14 | Percentage of Participants Alive and Discharged From the Hospital Through Day 28 | No | 1 Participants |
| IC14 | Percentage of Participants Alive and Discharged From the Hospital Through Day 28 | Yes | 19 Participants |
| Placebo | Percentage of Participants Alive and Discharged From the Hospital Through Day 28 | Yes | 19 Participants |
| Placebo | Percentage of Participants Alive and Discharged From the Hospital Through Day 28 | No | 1 Participants |
Comparison: All categories included in the analysis.p-value: 1Fisher Exact
Secondary
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: 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
Time frame: Within the 28 day period following baseline.
Population: Modified Intent to Treat population (mITT), that included all participants who were randomized and treated with at least one dose of investigational product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IC14 | Percentage of Participants Alive and Free of Any Episode of Acute Respiratory Failure Through Day 28 | Yes | 18 Participants |
| IC14 | Percentage of Participants Alive and Free of Any Episode of Acute Respiratory Failure Through Day 28 | No | 2 Participants |
| Placebo | Percentage of Participants Alive and Free of Any Episode of Acute Respiratory Failure Through Day 28 | Yes | 18 Participants |
| Placebo | Percentage of Participants Alive and Free of Any Episode of Acute Respiratory Failure Through Day 28 | No | 2 Participants |
Comparison: All categories included in the anlysis.p-value: 1Fisher Exact
Secondary
Percentage of Participants Alive and Free of Invasive Mechanical Ventilation Through Day 28
Endotracheal intubation and mechanical ventilation.
Time frame: Within the 28 day period following baseline.
Population: Modified Intent to Treat population (mITT), that included all participants who were randomized and treated with at least one dose of investigational product.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IC14 | Percentage of Participants Alive and Free of Invasive Mechanical Ventilation Through Day 28 | Yes | 19 Participants |
| IC14 | Percentage of Participants Alive and Free of Invasive Mechanical Ventilation Through Day 28 | No | 1 Participants |
| Placebo | Percentage of Participants Alive and Free of Invasive Mechanical Ventilation Through Day 28 | Yes | 19 Participants |
| Placebo | Percentage of Participants Alive and Free of Invasive Mechanical Ventilation Through Day 28 | No | 1 Participants |
Comparison: All categories included in the analysis.p-value: 1Fisher Exact
Secondary
Percent of Participants Who Begin Corticosteroid Therapy for Worsening COVID-19 Illness After Randomization
Initiation of corticosteroid therapy.
Time frame: Within the 28 day period following baseline.
Population: Modified Intent to Treat population (mITT), that included all participants who were randomized and treated with at least one dose of investigational product.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IC14 | Percent of Participants Who Begin Corticosteroid Therapy for Worsening COVID-19 Illness After Randomization | Yes | 1 Participants |
| IC14 | Percent of Participants Who Begin Corticosteroid Therapy for Worsening COVID-19 Illness After Randomization | No | 19 Participants |
| Placebo | Percent of Participants Who Begin Corticosteroid Therapy for Worsening COVID-19 Illness After Randomization | Yes | 1 Participants |
| Placebo | Percent of Participants Who Begin Corticosteroid Therapy for Worsening COVID-19 Illness After Randomization | No | 19 Participants |
Comparison: All categories included in the analysis.p-value: 1Fisher Exact
Secondary
Serious Adverse Events (SAEs)
Number of serious adverse events
Time frame: Within the 28 day period following baseline.
Population: All participants who initiated study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IC14 | Serious Adverse Events (SAEs) | 6 Serious Adverse Events |
| Placebo | Serious Adverse Events (SAEs) | 4 Serious Adverse Events |