COVID-19
Conditions
Keywords
Coronavirus Disease, Severe acute respiratory syndrome coronavirus 2, SARS-CoV-2
Brief summary
The purpose of the study is to determine if Liquid Alpha1-Proteinase Inhibitor (Human) (Liquid Alpha1-PI) plus SMT can reduce the proportion of participants dying or requiring intensive care unit (ICU) admission on or before Day 29 or who are dependent on high flow oxygen devices or invasive mechanical ventilation on Day 29 versus placebo plus SMT in hospitalized participants with COVID-19.
Interventions
Intravenous infusion 120 mg/kg
DRUGPlacebo
Intravenous infusion
DRUGStandard Medical Treatment
SMT
Sponsors
Grifols Therapeutics LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Hospitalized male or female participant ≥ 18 years of age at time of screening who is being treated for COVID-19. Participants must be screened within 48 hours (≤ 48 hours) of hospital admission. 2. Has laboratory-confirmed novel coronavirus {SARS-CoV-2} infection as determined by qualitative polymerase chain reaction (PCR) (reverse transcriptase \[RT\]-PCR), or other commercial or public health assay approved by regulatory authorities as a diagnostic test for COVID-19 in any specimen during the current hospital admission OR 96 hours prior to the hospital admission date and prior to randomization (the SARS-CoV-2 test results must be performed by a hospital laboratory and the documentation available). 3. COVID-19 illness (symptoms) of any duration, including both of the following: a) Radiographic infiltrates by imaging (chest X-Ray, computed tomography (CT) scan, etc.) and/or clinical assessment (evidence of rales/crackles on exam) with peripheral oxygen saturation by pulse oximetry (SpO2) \<94% on room air; b) Any one of the following related to COVID-19: i. Ferritin \> 400 nanogram per milliliter (ng/mL), ii. lactate dehydrogenase (LDH) \> 300 units per liter (U/L), iii. D-Dimers \> reference range, or iv. C-reactive protein (CRP) \> 40 milligram per liter (mg/L). 4. Participant provides informed consent prior to initiation of any study procedures. 5. Female participants of childbearing potential (and males with female partners of childbearing potential) must agree to use of acceptable contraception methods during study (example, oral, injectable, or implanted hormonal methods of contraception, placement of an intrauterine device or intrauterine system, condom or occlusive cap with spermicidal foam/gel/film/cream/suppository, male sterilization, or true abstinence) throughout the study.
Exclusion criteria
1. Participants requiring invasive mechanical ventilation or ICU admission or with partial pressure of arterial oxygen/ fraction of inspired oxygen (PaO2/FIO2) ≤ 150 mmHg (i.e., arterial oxygen in millimeter of mercury (mmHg) divided by fraction inspired oxygen concentration \[example, 0.21 for room air\]). 2. Clinical evidence of any significant acute or chronic disease that, in the opinion of the investigator, may place the participant at undue medical risk. 3. The participant has had a known serious anaphylactic reaction to blood, any blood-derived or plasma product, or known selective immunoglobulin A (IgA) deficiency with anti-IgA antibodies. 4. A medical condition in which the infusion of additional fluid is contraindicated (example, decompensated congestive heart failure or renal failure with fluid overload). This includes currently uncontrolled congestive heart failure New York Heart Association Class III or IV stage heart failure. 5. Shock that is unresponsive to fluid challenge and/or multiple vasopressors and accompanied by multiorgan failure considered not able to be reversed by the Principal Investigator. 6. Known alpha-1 antitrypsin deficiency for which the participant is already receiving alpha1-proteinase inhibitor augmentation therapy. 7. Women who are pregnant or breastfeeding. Female participants of child-bearing potential must have a negative test for pregnancy blood or urine human chorionic gonadotropin (HCG)-based assay at screening/baseline visit. 8. Participants for whom there is limitation of therapeutic effort such as Do not resuscitate status. 9. Currently participating in another interventional clinical trial with investigational medical product or device. 10. Participants previously requiring long-term oxygen therapy (home oxygen therapy). 11. History (within the last 2 years) of myocardial infarction, unstable angina, stroke or transient ischemic attacks, pulmonary embolism or deep venous thrombosis. 12. Participant has medical condition (other than COVID-19) that is projected to limit lifespan to ≤ 1 year. 13. Systolic blood pressure \< 100 mm Hg or \> 160 mm Hg (uncontrolled hypertension) at the time of Screening. 14. Alanine aminotransferase (ALT) ≥ 2 times the upper limit of normal (ULN). 15. Any elevation of total bilirubin at the time of Screening. 16. Estimated glomerular filtration rate (eGFR) \< 45 mL/min (or participant is dependent on dialysis/renal replacement therapy) at the time of Screening. eGFR is calculated by the Cockcroft-Gault equation. 17. Hemoglobin \< 10 g/dL at the time of Screening. 18. Absolute neutrophil count \< 1000/mm\^3 at the time of Screening. 19. Platelet count \< 75,000/mm\^3 at the time of Screening. 20. Participant has history of drug or alcohol abuse within the past 24 months. 21. Participant is unwilling to commit to follow-up visits. 22. Known history of prothrombin gene mutation 20210, homozygous Factor V Leiden mutations, antithrombin III deficiency, protein C deficiency, protein S deficiency or antiphospholipid syndrome.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants Dying or Requiring Intensive Care Unit (ICU) Admission | Up to Day 29 |
| Percentage of Participants Who Are Dependent on High Flow Oxygen Devices or Invasive Mechanical Ventilation | Day 29 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Hospital Discharge | Up to Day 29 | Time to hospital discharge is defined as duration of hospitalization from Day 1 through Day 29. |
| Duration of ICU Stay | Up to Day 29 | Duration of ICU stay in days is analyzed for participants admitted to ICU post randomization. |
| Duration of Any Oxygen Use | Up to Day 30 | — |
| Duration of Mechanical Ventilation | Up to Day 29 | Duration of Mechanical Ventilation is analyzed for participants requiring mechanical ventilation post randomization. |
| Mean Change From Baseline in Ordinal Scale | Baseline, Days 15 and 29 | The ordinal scale is a 7-point scale ranging from 1 to 7 used to measure clinical status based on the following points: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities. Higher score indicated no severe illness. Mean change in Ordinal scale was evaluated by fitting a linear mixed-effects model for repeated measures (MMRM). |
| Change From Baseline in National Early Warning Score (NEWS) | Baseline, Days 15 and 29 | NEWS is clinical scoring developed to improve detection of deterioration in ill participant. It is based on 7 clinical parameters: Respiration rate, oxygen saturation, supplemental oxygen, systolic blood pressure (BP), pulse rate, level of consciousness, and temperature. A score of 0 and 2 was allocated to supplemental oxygen, 0 and 3 for level of consciousness and score of 0, 1, 2 and 3 for remaining parameters (i.e. respiration rate, oxygen saturation, systolic BP, pulse rate and temperature) where 0 = normal health condition to 3 = worst health condition; Higher scores indicated more severity. All scores were summed to get an aggregate score. Aggregate NEWS score ranged from 0 to 20, with higher scores indicating more severity/higher risk. |
| Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale | Day 15 and Day 29 | The ordinal scale is a 7-point scale ranging from 1 to 7 used to measure clinical status based on the following points: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or ECMO 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities. The percentages are rounded off to the single decimal point. |
| Time to Sustained Normalization of Temperature | Up to Day 29 | Time to sustained normalization of temperature was reported at 50th percentile in days. |
| Percentage of Participants Who Experienced Sustained Normalization of Fever | Up to Day 29 | Normalization of fever is defined as temperature \< 36.6 °C armpit, \< 37.2 °C oral, or \< 37.8 °C rectal sustained for at least 24 hours. |
| Number of Participants Who Develop Acute Respiratory Distress Syndrome (ARDS) | Up to Day 29 | ARDS was defined based on Berlin criteria (chest imaging, origin of edema, oxygenation). |
| Time to Clinical Progression | Up to Day 29 | Time to clinical progression is defined as the time to death, mechanical ventilation, or ICU admission. Time to clinical progression was reported at 50th percentile in days. |
| Absolute Change From Baseline in Ordinal Scale | Baseline, Days 15 and 29 | The ordinal scale is a 7-point scale ranging from 1 to 7 used to measure clinical status based on the following points: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or ECMO; 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities. Higher score indicated no severe illness. |
| Time to Clinical Response as Assessed by NEWS Score ≤ 2 Maintained for 24 Hours | Up to Day 29 | Time to clinical response was reported at 50th percentile in days. |
Countries
Brazil, Chile, Colombia, Mexico, United States
Participant flow
Recruitment details
Participants took part in the study at sites in the United States, Brazil, Chile, Colombia, and Mexico, from 29 January 2021 (first participant enrolled to receive the study drug) to 28 January 2022 (last participant completed).
Pre-assignment details
78 participants with Coronavirus Disease 2019 (COVID-19) who were hospitalized were screened of which 57 were randomized in 1:1 ratio to receive either Alpha1-Proteinase Inhibitor (PI) (Human) plus Standard Medical Treatment (SMT) or placebo plus Standard Medical Treatment.
Participants by arm
| Arm | Count |
|---|---|
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment Participants received the first IV infusion of liquid alpha1-proteinase inhibitor (human) 120 mg/kg, based on body weight on Day 1, followed by second liquid alpha1-proteinase inhibitor (human) dose of 120 mg/kg based on body weight, on Day 8 (second dose was not mandatory and was given at the PI's discretion). Participants also received all standard of care interventions while hospitalized, from Day 1 to Day 29. | 29 |
| Placebo + Standard Medical Treatment Participants received IV infusions of 0.9% normal saline of commensurate volume to that of liquid alpha1-proteinase inhibitor as placebo on Day 1 and Day 8 (Day 8 was not mandatory and was given at the PI's discretion). Participants also received all standard of care interventions while hospitalized, from Day 1 to Day 29. | 28 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Death | 2 | 1 |
| Overall Study | Lost to Follow-up | 3 | 1 |
| Overall Study | Physician Decision (Does not Include Adverse Events) | 0 | 1 |
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Reason Not Specified | 4 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Placebo + Standard Medical Treatment | Total |
|---|---|---|---|
| Age, Continuous | 52.1 years STANDARD_DEVIATION 14.46 | 51.2 years STANDARD_DEVIATION 12.14 | 51.7 years STANDARD_DEVIATION 13.26 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 10 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 18 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Asian | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Black or African American | 1 Participants | 5 Participants | 6 Participants |
| Race/Ethnicity, Customized Race Other | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Race White | 22 Participants | 21 Participants | 43 Participants |
| Sex: Female, Male Female | 14 Participants | 11 Participants | 25 Participants |
| Sex: Female, Male Male | 15 Participants | 17 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 29 | 1 / 28 |
| other Total, other adverse events | 2 / 27 | 8 / 27 |
| serious Total, serious adverse events | 5 / 27 | 5 / 27 |
Outcome results
Primary
Percentage of Participants Dying or Requiring Intensive Care Unit (ICU) Admission
Time frame: Up to Day 29
Population: ITT population included all participants who were randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Percentage of Participants Dying or Requiring Intensive Care Unit (ICU) Admission | Percentage of Participants Dying | 6.9 percentage of participants |
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Percentage of Participants Dying or Requiring Intensive Care Unit (ICU) Admission | Percentage of Participants Requiring ICU Admission | 20.7 percentage of participants |
| Placebo + Standard Medical Treatment | Percentage of Participants Dying or Requiring Intensive Care Unit (ICU) Admission | Percentage of Participants Dying | 3.6 percentage of participants |
| Placebo + Standard Medical Treatment | Percentage of Participants Dying or Requiring Intensive Care Unit (ICU) Admission | Percentage of Participants Requiring ICU Admission | 14.3 percentage of participants |
Comparison: Percentage of Participants Dying
Comparison: Percentage of Participants Requiring ICU Admission
Primary
Percentage of Participants Who Are Dependent on High Flow Oxygen Devices or Invasive Mechanical Ventilation
Time frame: Day 29
Population: ITT population included all participants who were randomized. Percentage of participants are rounded off to the single decimal point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Percentage of Participants Who Are Dependent on High Flow Oxygen Devices or Invasive Mechanical Ventilation | Dependent on High Flow Oxygen Devices | 6.9 percentage of participants |
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Percentage of Participants Who Are Dependent on High Flow Oxygen Devices or Invasive Mechanical Ventilation | Dependent on Invasive Mechanical Ventilation | 3.4 percentage of participants |
| Placebo + Standard Medical Treatment | Percentage of Participants Who Are Dependent on High Flow Oxygen Devices or Invasive Mechanical Ventilation | Dependent on High Flow Oxygen Devices | 0.0 percentage of participants |
| Placebo + Standard Medical Treatment | Percentage of Participants Who Are Dependent on High Flow Oxygen Devices or Invasive Mechanical Ventilation | Dependent on Invasive Mechanical Ventilation | 0.0 percentage of participants |
Comparison: Percentage of Participants Who are Dependent on High Flow Oxygen Devices
Comparison: Percentage of Participants Who are Dependent on Invasive Mechanical Ventilation
Secondary
Absolute Change From Baseline in Ordinal Scale
The ordinal scale is a 7-point scale ranging from 1 to 7 used to measure clinical status based on the following points: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or ECMO; 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities. Higher score indicated no severe illness.
Time frame: Baseline, Days 15 and 29
Population: ITT population included all participants who were randomized. Overall number of participants analyzed signifies the number of participants with available data for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Absolute Change From Baseline in Ordinal Scale | Change From Baseline at Day 29 | 1.8 score on a scale | Standard Deviation 1.87 |
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Absolute Change From Baseline in Ordinal Scale | Change From Baseline at Day 15 | 1.5 score on a scale | Standard Deviation 1.96 |
| Placebo + Standard Medical Treatment | Absolute Change From Baseline in Ordinal Scale | Change From Baseline at Day 15 | 2.3 score on a scale | Standard Deviation 1.67 |
| Placebo + Standard Medical Treatment | Absolute Change From Baseline in Ordinal Scale | Change From Baseline at Day 29 | 2.7 score on a scale | Standard Deviation 1.48 |
Secondary
Change From Baseline in National Early Warning Score (NEWS)
NEWS is clinical scoring developed to improve detection of deterioration in ill participant. It is based on 7 clinical parameters: Respiration rate, oxygen saturation, supplemental oxygen, systolic blood pressure (BP), pulse rate, level of consciousness, and temperature. A score of 0 and 2 was allocated to supplemental oxygen, 0 and 3 for level of consciousness and score of 0, 1, 2 and 3 for remaining parameters (i.e. respiration rate, oxygen saturation, systolic BP, pulse rate and temperature) where 0 = normal health condition to 3 = worst health condition; Higher scores indicated more severity. All scores were summed to get an aggregate score. Aggregate NEWS score ranged from 0 to 20, with higher scores indicating more severity/higher risk.
Time frame: Baseline, Days 15 and 29
Population: ITT population included all participants who were randomized. Overall number analyzed are the number of participants with data available for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Change From Baseline in National Early Warning Score (NEWS) | Change From Baseline at Day 15 | -1.1 score on a scale | Standard Deviation 3.71 |
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Change From Baseline in National Early Warning Score (NEWS) | Change From Baseline at Day 29 | -2.9 score on a scale | Standard Deviation 2.38 |
| Placebo + Standard Medical Treatment | Change From Baseline in National Early Warning Score (NEWS) | Change From Baseline at Day 15 | -2.3 score on a scale | Standard Deviation 2.22 |
| Placebo + Standard Medical Treatment | Change From Baseline in National Early Warning Score (NEWS) | Change From Baseline at Day 29 | -2.5 score on a scale | Standard Deviation 1.95 |
Comparison: Day 15p-value: 0.145395% CI: [-0.43, 2.87]Kenward-Roger
Comparison: Day 29p-value: 0.801595% CI: [-1.44, 1.86]Kenward-Roger
Secondary
Duration of Any Oxygen Use
Time frame: Up to Day 30
Population: ITT population included all participants who were randomized. Overall number of participants analyzed signifies the number of participants with available data for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Duration of Any Oxygen Use | 7.0 days |
| Placebo + Standard Medical Treatment | Duration of Any Oxygen Use | 6.0 days |
p-value: 0.332995% CI: [-2.92, 8.48]ANOVA
Secondary
Duration of ICU Stay
Duration of ICU stay in days is analyzed for participants admitted to ICU post randomization.
Time frame: Up to Day 29
Population: ITT population included all participants who were randomized. Overall number of participants analyzed signifies the number of participants with available data for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Duration of ICU Stay | 0.0 days |
| Placebo + Standard Medical Treatment | Duration of ICU Stay | 0.0 days |
p-value: 0.122195% CI: [-0.94, 7.76]ANOVA
Secondary
Duration of Mechanical Ventilation
Duration of Mechanical Ventilation is analyzed for participants requiring mechanical ventilation post randomization.
Time frame: Up to Day 29
Population: ITT population included all participants who were randomized. Overall number of participants analyzed signifies the number of participants with available data for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Duration of Mechanical Ventilation | 0.0 days |
| Placebo + Standard Medical Treatment | Duration of Mechanical Ventilation | 0.0 days |
p-value: 0.109295% CI: [-0.81, 7.77]ANOVA
Secondary
Mean Change From Baseline in Ordinal Scale
The ordinal scale is a 7-point scale ranging from 1 to 7 used to measure clinical status based on the following points: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities. Higher score indicated no severe illness. Mean change in Ordinal scale was evaluated by fitting a linear mixed-effects model for repeated measures (MMRM).
Time frame: Baseline, Days 15 and 29
Population: ITT population included all participants who were randomized. Overall number of participants analyzed signifies the number of participants with available data for analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Mean Change From Baseline in Ordinal Scale | Change From Baseline at Day 15 | 1.58 score on a scale |
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Mean Change From Baseline in Ordinal Scale | Change From Baseline at Day 29 | 1.80 score on a scale |
| Placebo + Standard Medical Treatment | Mean Change From Baseline in Ordinal Scale | Change From Baseline at Day 15 | 2.21 score on a scale |
| Placebo + Standard Medical Treatment | Mean Change From Baseline in Ordinal Scale | Change From Baseline at Day 29 | 2.66 score on a scale |
Comparison: Day 15p-value: 0.118995% CI: [-1.43, 0.17]Kenward-Roger
Comparison: Day 29p-value: 0.034195% CI: [-1.64, -0.07]Kenward-Roger
Secondary
Number of Participants Who Develop Acute Respiratory Distress Syndrome (ARDS)
ARDS was defined based on Berlin criteria (chest imaging, origin of edema, oxygenation).
Time frame: Up to Day 29
Population: ITT population included all participants who were randomized. Overall number of participants analyzed are the participants assessed for ARDS by Berlin criteria.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Number of Participants Who Develop Acute Respiratory Distress Syndrome (ARDS) | 5 Participants |
| Placebo + Standard Medical Treatment | Number of Participants Who Develop Acute Respiratory Distress Syndrome (ARDS) | 2 Participants |
Secondary
Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale
The ordinal scale is a 7-point scale ranging from 1 to 7 used to measure clinical status based on the following points: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or ECMO 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities. The percentages are rounded off to the single decimal point.
Time frame: Day 15 and Day 29
Population: ITT population included all participants who were randomized. Overall number of participants analyzed are unique number of participants with available data for analysis. Number analyzed are unique number of participants out of all the assessed participants with data available at the specified timepoint. Different participants may have contributed data for each timepoint. Participants who died during the study were assigned a value of 1 for the ordinal scale at every timepoint after the death.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale | Day 15: Hospitalized, requiring supplemental oxygen | 10.0 percentage of participants |
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale | Day 15: Death | 5.0 percentage of participants |
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale | Day 29: Hospitalized, on invasive mechanical ventilation or ECMO | 0.0 percentage of participants |
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale | Day 15: Hospitalized, not requiring supplemental oxygen | 0.0 percentage of participants |
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale | Day 29: Hospitalized, on non-invasive ventilation or high flow oxygen devices | 4.8 percentage of participants |
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale | Day 15: Hospitalized, on non-invasive ventilation or high flow oxygen devices | 5.0 percentage of participants |
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale | Day 29: Hospitalized, requiring supplemental oxygen | 4.8 percentage of participants |
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale | Day 15: Not hospitalized, limitation on activities | 25.0 percentage of participants |
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale | Day 29: Hospitalized, not requiring supplemental oxygen | 0.0 percentage of participants |
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale | Day 15: Hospitalized, on invasive mechanical ventilation or ECMO | 10.0 percentage of participants |
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale | Day 29: Not hospitalized, limitation on activities | 38.1 percentage of participants |
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale | Day 15: Not hospitalized, no limitations on activities | 45.0 percentage of participants |
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale | Day 29: Not hospitalized, no limitations on activities | 42.9 percentage of participants |
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale | Day 29: Death | 9.5 percentage of participants |
| Placebo + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale | Day 29: Not hospitalized, no limitations on activities | 78.3 percentage of participants |
| Placebo + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale | Day 15: Death | 4.5 percentage of participants |
| Placebo + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale | Day 15: Hospitalized, on invasive mechanical ventilation or ECMO | 0.0 percentage of participants |
| Placebo + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale | Day 15: Hospitalized, on non-invasive ventilation or high flow oxygen devices | 4.5 percentage of participants |
| Placebo + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale | Day 15: Hospitalized, requiring supplemental oxygen | 4.5 percentage of participants |
| Placebo + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale | Day 15: Hospitalized, not requiring supplemental oxygen | 4.5 percentage of participants |
| Placebo + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale | Day 15: Not hospitalized, limitation on activities | 22.7 percentage of participants |
| Placebo + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale | Day 15: Not hospitalized, no limitations on activities | 59.1 percentage of participants |
| Placebo + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale | Day 29: Death | 4.3 percentage of participants |
| Placebo + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale | Day 29: Hospitalized, on invasive mechanical ventilation or ECMO | 0.0 percentage of participants |
| Placebo + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale | Day 29: Hospitalized, on non-invasive ventilation or high flow oxygen devices | 0.0 percentage of participants |
| Placebo + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale | Day 29: Hospitalized, requiring supplemental oxygen | 0.0 percentage of participants |
| Placebo + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale | Day 29: Hospitalized, not requiring supplemental oxygen | 0.0 percentage of participants |
| Placebo + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale | Day 29: Not hospitalized, limitation on activities | 17.4 percentage of participants |
Secondary
Percentage of Participants Who Experienced Sustained Normalization of Fever
Normalization of fever is defined as temperature \< 36.6 °C armpit, \< 37.2 °C oral, or \< 37.8 °C rectal sustained for at least 24 hours.
Time frame: Up to Day 29
Population: ITT population included all participants who were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Percentage of Participants Who Experienced Sustained Normalization of Fever | 44.8 percentage of participants |
| Placebo + Standard Medical Treatment | Percentage of Participants Who Experienced Sustained Normalization of Fever | 42.9 percentage of participants |
p-value: 0.880995% CI: [-24.1, 28.3]Chi-squared
Secondary
Time to Clinical Progression
Time to clinical progression is defined as the time to death, mechanical ventilation, or ICU admission. Time to clinical progression was reported at 50th percentile in days.
Time frame: Up to Day 29
Population: ITT population included all participants who were randomized. Overall number of participants analyzed are the participants with clinical progression.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Time to Clinical Progression | NA days |
| Placebo + Standard Medical Treatment | Time to Clinical Progression | NA days |
Secondary
Time to Clinical Response as Assessed by NEWS Score ≤ 2 Maintained for 24 Hours
Time to clinical response was reported at 50th percentile in days.
Time frame: Up to Day 29
Population: ITT population included all participants who were randomized. Overall number analyzed are the participants who achieved clinical response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Time to Clinical Response as Assessed by NEWS Score ≤ 2 Maintained for 24 Hours | NA days |
| Placebo + Standard Medical Treatment | Time to Clinical Response as Assessed by NEWS Score ≤ 2 Maintained for 24 Hours | NA days |
Secondary
Time to Hospital Discharge
Time to hospital discharge is defined as duration of hospitalization from Day 1 through Day 29.
Time frame: Up to Day 29
Population: ITT population included all participants who were randomized. Overall number of participants analyzed signifies the number of participants with available data for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Time to Hospital Discharge | 5.0 days |
| Placebo + Standard Medical Treatment | Time to Hospital Discharge | 5.0 days |
p-value: 0.513595% CI: [-3.04, 6]ANOVA
Secondary
Time to Sustained Normalization of Temperature
Time to sustained normalization of temperature was reported at 50th percentile in days.
Time frame: Up to Day 29
Population: ITT population included all participants who were randomized. Participants who achieved sustained normalization of temperature were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Alpha1-Proteinase Inhibitor + Standard Medical Treatment | Time to Sustained Normalization of Temperature | 7 days |
| Placebo + Standard Medical Treatment | Time to Sustained Normalization of Temperature | NA days |