Study to Evaluate the Safety and Efficacy of Liquid Alpha... | NCT04547140

NCT04547140

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Liquid Alpha1-Proteinase Inhibitor + Standard Medical Treatment	Experimental	Participants received the first intravenous (IV) infusion of liquid alpha1-proteinase inhibitor (human) 120 milligrams per kilogram (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 principal investigator's [PI] discretion). Participants also received all standard of care interventions while hospitalized, from Day 1 to Day 29.	Biological: Liquid Alpha1-Proteinase Inhibitor (Human) Drug: Standard Medical Treatment
Placebo + Standard Medical Treatment	Placebo Comparator	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.	Drug: Placebo Drug: Standard Medical Treatment

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Liquid Alpha1-Proteinase Inhibitor (Human)	Biological	Intravenous infusion 120 mg/kg	Liquid Alpha1-Proteinase Inhibitor + Standard Medical Treatment

Outcomes Module

Primary Outcomes

Measure	Description	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 Outcomes

Measure	Description	Time Frame
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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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.
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).
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).
Participant provides informed consent prior to initiation of any study procedures.
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:

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]).
Clinical evidence of any significant acute or chronic disease that, in the opinion of the investigator, may place the participant at undue medical risk.
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.
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.
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.
Known alpha-1 antitrypsin deficiency for which the participant is already receiving alpha1-proteinase inhibitor augmentation therapy.
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.
Participants for whom there is limitation of therapeutic effort such as "Do not resuscitate" status.
Currently participating in another interventional clinical trial with investigational medical product or device.
Participants previously requiring long-term oxygen therapy (home oxygen therapy).
History (within the last 2 years) of myocardial infarction, unstable angina, stroke or transient ischemic attacks, pulmonary embolism or deep venous thrombosis.
Participant has medical condition (other than COVID-19) that is projected to limit lifespan to ≤ 1 year.
Systolic blood pressure < 100 mm Hg or > 160 mm Hg (uncontrolled hypertension) at the time of Screening.
Alanine aminotransferase (ALT) ≥ 2 times the upper limit of normal (ULN).
Any elevation of total bilirubin at the time of Screening.
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.
Hemoglobin < 10 g/dL at the time of Screening.
Absolute neutrophil count < 1000/mm^3 at the time of Screening.
Platelet count < 75,000/mm^3 at the time of Screening.
Participant has history of drug or alcohol abuse within the past 24 months.
Participant is unwilling to commit to follow-up visits.
Known history of prothrombin gene mutation 20210, homozygous Factor V Leiden mutations, antithrombin III deficiency, protein C deficiency, protein S deficiency or antiphospholipid syndrome.

Contacts/Locations Module

Facility	Status	City	State	ZIP	Country	Contacts
Birmingham VA		Birmingham	Alabama	35233	United States
St. Joseph's Hospital

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Alpha1-Proteinase Inhibitor + Standard Medical Treatment	Participants received the first intravenous (IV) infusion of liquid alpha1-proteinase inhibitor (human) 120 milligrams per kilogram (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 principal investigator's [PI] discretion). Participants also received all standard of care interventions while hospitalized, from Day 1 to Day 29.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Dec 8, 2021	Dec 13, 2022

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

Masking Info

Alpha1-proteinase inhibitor

Intent-to-Treat (ITT) population included all participants who were randomized.

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	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.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00052.1± 14.46 BG00151.2± 12.14 BG00251.7± 13.26

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00014 BG00111 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00014 BG00110 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Race

Title	Measurements
White	BG00022 BG00121 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants Dying or Requiring Intensive Care Unit (ICU) Admission

ITT population included all participants who were randomized.

Posted

Number

percentage of participants

Up to Day 29

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG00029 OG00128

Title

Denominators

Categories

Percentage of Participants Dying

Title	Measurements
	OG0006.9 OG0013.6

Percentage of Participants Requiring ICU Admission

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Percentage of Participants Dying					Difference in percentages	3.3			2-Sided								Superiority
OG000 OG001	Percentage of Participants Requiring ICU Admission

Primary

Percentage of Participants Who Are Dependent on High Flow Oxygen Devices or Invasive Mechanical Ventilation

ITT population included all participants who were randomized. Percentage of participants are rounded off to the single decimal point.

Posted

Number

percentage of participants

Day 29

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants

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.

ITT population included all participants who were randomized. Overall number analyzed are the number of participants with data available for analysis.

Posted

Mean

Standard Deviation

score on a scale

Baseline, Days 15 and 29

ID	Title	Description
OG000	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.
OG001	Placebo + Standard Medical Treatment

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.

ITT population included all participants who were randomized. Overall number analyzed are the participants who achieved clinical response.

Posted

Median

95% Confidence Interval

days

Up to Day 29

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Time to Hospital Discharge

Time to hospital discharge is defined as duration of hospitalization from Day 1 through Day 29.

ITT population included all participants who were randomized. Overall number of participants analyzed signifies the number of participants with available data for analysis.

Posted

Median

Full Range

days

Up to Day 29

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Duration of ICU Stay

Duration of ICU stay in days is analyzed for participants admitted to ICU post randomization.

ITT population included all participants who were randomized. Overall number of participants analyzed signifies the number of participants with available data for analysis.

Posted

Median

Full Range

days

Up to Day 29

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Duration of Any Oxygen Use

ITT population included all participants who were randomized. Overall number of participants analyzed signifies the number of participants with available data for analysis.

Posted

Median

Full Range

days

Up to Day 30

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants

Secondary

Duration of Mechanical Ventilation

Duration of Mechanical Ventilation is analyzed for participants requiring mechanical ventilation post randomization.

ITT population included all participants who were randomized. Overall number of participants analyzed signifies the number of participants with available data for analysis.

Posted

Median

Full Range

days

Up to Day 29

ID	Title	Description
OG000	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.
OG001	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.

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).

ITT population included all participants who were randomized. Overall number of participants analyzed signifies the number of participants with available data for analysis.

Posted

Least Squares Mean

95% Confidence Interval

score on a scale

Baseline, Days 15 and 29

ID	Title	Description
OG000	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.
OG001	Placebo + Standard Medical Treatment

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.

ITT population included all participants who were randomized. Overall number of participants analyzed signifies the number of participants with available data for analysis.

Posted

Mean

Standard Deviation

score on a scale

Baseline, Days 15 and 29

ID	Title	Description
OG000	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.
OG001	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.

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.

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.

Posted

Number

percentage of participants

Day 15 and Day 29

ID	Title	Description
OG000	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.

Secondary

Time to Sustained Normalization of Temperature

Time to sustained normalization of temperature was reported at 50th percentile in days.

ITT population included all participants who were randomized. Participants who achieved sustained normalization of temperature were analyzed.

Posted

Median

95% Confidence Interval

days

Up to Day 29

ID	Title	Description
OG000	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.
OG001	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.

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.

ITT population included all participants who were randomized.

Posted

Number

95% Confidence Interval

percentage of participants

Up to Day 29

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Number of Participants Who Develop Acute Respiratory Distress Syndrome (ARDS)

ARDS was defined based on Berlin criteria (chest imaging, origin of edema, oxygenation).

ITT population included all participants who were randomized. Overall number of participants analyzed are the participants assessed for ARDS by Berlin criteria.

Posted

Count of Participants

Participants

Up to Day 29

ID	Title	Description
OG000	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.
OG001	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.

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.

ITT population included all participants who were randomized. Overall number of participants analyzed are the participants with clinical progression.

Posted

Median

95% Confidence Interval

days

Up to Day 29

ID	Title	Description
OG000	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.
OG001	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.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	2	29	5	27	2	27
EG001	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.	1	28	5	27	8	27

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Tracheal injury	Injury, poisoning and procedural complications	MedDRA (23.0)	Systematic Assessment	EG0001 affected27 at risk EG0010 affected27 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (23.0)	Systematic Assessment	EG0001 affected27 at risk EG0010 affected27 at risk
Seizure	Nervous system disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected27 at risk EG0011 affected27 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA (23.0)	Systematic Assessment	EG0001 affected27 at risk EG0010 affected27 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0001 affected27 at risk EG0010 affected27 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected27 at risk EG0011 affected27 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0002 affected27 at risk EG0011 affected27 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0002 affected27 at risk EG0012 affected27 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Bradycardia	Cardiac disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected27 at risk EG0013 affected27 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected27 at risk EG0012 affected27 at risk
Nausea	Gastrointestinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected27 at risk EG0012 affected27 at risk
Pneumonia bacterial	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0002 affected27 at risk EG0010 affected27 at risk
Blood pressure increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected27 at risk EG0012 affected27 at risk

Study was early terminated due to lack of efficacy (futility).

Certain Agreements

First MCP Posted Date

ID	Term
D000086382	COVID-19

Ancestor Terms

ID	Term
D011024	Pneumonia, Viral
D011014	Pneumonia
D012141	Respiratory Tract Infections
D007239	Infections
D014777	Virus Diseases
D018352	Coronavirus Infections
D003333	Coronaviridae Infections
D030341	Nidovirales Infections
D012327	RNA Virus Infections
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
D000515	alpha 1-Antitrypsin
D000077330	Saline Solution

Ancestor Terms

ID	Term
D006023	Glycoproteins
D006001	Glycoconjugates
D002241	Carbohydrates
D015843	Serpins
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D000209	Acute-Phase Proteins
D001798	Blood Proteins
D011506	Proteins
D000510	Alpha-Globulins
D012712	Serum Globulins
D005916	Globulins
D000077324	Crystalloid Solutions
D007552	Isotonic Solutions
D012996	Solutions
D004364	Pharmaceutical Preparations

Units	Counts
Participants	OG0006 OG0014