Coronavirus Disease 2019 (COVID-19)
Conditions
Keywords
Prevention of respiratory failure
Brief summary
This is a prospective, phase 2, multicenter, randomized, double blind, placebo controlled, parallel group study to assess the safety and efficacy of CSL312 administered intravenously, in combination with standard of care (SOC) treatment, in patients with Coronavirus disease 2019 (COVID 19)
Interventions
BIOLOGICALGaradacimab, Factor XIIa Antagonist Monoclonal Antibody
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
DRUGPlacebo
CSL312 diluent administered intravenously
Sponsors
CSL Behring
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection as determined using a molecular diagnostic test (reverse transcription polymerase chain reaction \[RT-PCR\] or equivalent) approved by regulatory authorities (including Food and Drug Administration or Brazilian Health Regulatory Agency) or allowed under an emergency use authorization within 14 days before Screening. If a false negative result is suspected, the SARS-CoV-2 test may be repeated within the Screening Period. * Chest CT scan or X ray results confirming interstitial pneumonia * Severe COVID 19 disease as evidenced by ≥ 1 of the following criteria at Screening including within 24 hours before Screening: * Respiratory frequency \> 30 breaths per minute * SpO2 ≤ 93% on room air * Ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) \< 300 * Ratio of Arterial oxygen saturation to fraction of inspired oxygen (SaO2/FiO2 ratio) \< 218 (if PaO2/FiO2 ratio is not available) * Radiographic lung infiltrates \> 50%
Exclusion criteria
* Currently enrolled, planning to enroll, or participated, within the last 30 days, in a clinical study requiring administration of an IP, including expanded access or compassionate use with the only exception being administration of convalescent plasma. Administration of IP is permitted only if an emergency use authorization has been granted (eg, remdesivir). Additionally, off label use of approved drugs (eg, anti IL 6/anti IL 6R) is also permitted. * Pregnant or breastfeeding (female subjects) * Intubated and require mechanical ventilation (including ECMO) at the time of randomization * In the opinion of the investigator, the subject is expected to be intubated in the first 24 hours after IMP administration * Has a Do-Not-Intubate (DNI) or Do-Not-Resuscitate (DNR) order * In the opinion of the investigator, not expected to survive for \> 48 hours after admission * Presence of any of the following comorbid conditions prior to randomization and prior to SARS CoV 2 infection: * Severe heart failure (New York Heart Association Class IV) * End stage renal disease (Stage ≥ 4) or need for renal replacement therapy * Biopsy confirmed cirrhosis, portal hypertension, or hepatic encephalopathy * Malignancy (Stage IV) * Chronic lung disease requiring the use of oxygen at home * Active tuberculosis disease * Active bleeding or a current clinically significant coagulopathy (eg, international normalized ratio \[INR\] \> 1.5) or clinically significant risk for bleeding (eg, recent intracranial hemorrhage or bleeding peptic ulcer within the last 4 weeks) * History of venous thrombosis, myocardial infarction or cerebrovascular event within 3 months, or a prothrombotic disorder (eg, antithrombin III, protein C or protein S deficiency) * Known or suspected Grade 3 or 4 infusion-related reaction or hypersensitivity (per Common Terminology Criteria for Adverse Events \[CTCAE\]) to monoclonal antibody therapy, or hypersensitivity to the IMP or any excipients of the IMP * Currently receiving a therapy not permitted during the study. * Female subject of childbearing potential or fertile male subject either not using or not willing to use an acceptable method of contraception to avoid pregnancy during the study and for 90 days after receipt of the last dose of IMP * Any clinical or laboratory abnormality or other underlying conditions (eg, psychological disorders, substance abuse) that would render the subject unsuitable for participation in the study, in the opinion of the investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Percent of Participants With Tracheal Intubation or Death Prior to Tracheal Intubation | From randomization to Day 28 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants With Tracheal Intubation | From randomization to Day 28 | — |
| Number of Participants With ≥ 2-Point Improvement Compared to Baseline on National Institute of Allergy and Infectious Diseases (NIAID) Ordinal Scale | From randomization to Day 28 | The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. |
| Percent of Participants With ≥ 2-Point Improvement Compared to Baseline on NIAID | From randomization to Day 28 | The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. |
| Number of Participants Within Each of the Categories of the NIAID at End of Study | Day 28 | The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. |
| Percent of Participants Within Each of the Categories of the NIAID at End of Study | Day 28 | The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. |
| Percent of Participants Requiring Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BiPAP) | From randomization to Day 28 | — |
| Percent of Participants Requiring Extracorporeal Membrane Oxygenation (ECMO) | From randomization to Day 28 | None of the enrolled subjects required the use of ECMO during their participation in this study. Therefore, no data to report for this outcome measure. |
| Percent of Participants Requiring High-Flow Nasal Cannula (HFNC) | From randomization to Day 28 | — |
| Maximum Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score | From randomization to Day 28 | The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 (normal function) to 4 (most abnormal) with a total score ranging from 0 to 24. A high total SOFA score have been shown to be related to a worse outcome. |
| Change From Baseline in SOFA Total Score | From randomization to Day 28 | The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 (normal function) to 4 (most abnormal) with a total score ranging from 0 to 24. A high total SOFA score have been shown to be related to a worse outcome. |
| Change From Baseline in the Individual Components of SOFA Score | From randomization to Day 28 | The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 (normal function) to 4 (most abnormal) with a total score ranging from 0 to 24. A high total SOFA score have been shown to be related to a worse outcome. |
| Percent of Participants With Death From All Causes | From randomization to Day 28 | — |
| Number of Participants Experiencing Adverse Events (AEs) | Up to 28 days after CSL312 or placebo administration | — |
| Percent of Participants Experiencing AEs | Up to 28 days after CSL312 or placebo administration | — |
| Number of Participants Experiencing Serious Adverse Events (SAEs) | Up to 28 days after CSL312 or placebo administration | — |
| Percent of Participants Experiencing SAEs | Up to 28 days after CSL312 or placebo administration | — |
| Number of Participants With Adverse Events of Special Interest (AESIs) | Up to 28 days after CSL312 or placebo administration | — |
| Percent of Participants With AESIs | Up to 28 days after CSL312 or placebo administration | — |
| Number of Participants With Anti-CSL312 Antibodies | Up to 28 days after CSL312 or placebo administration | — |
| Maximum Plasma Concentration (Cmax) of CSL312 | Up to 28 days after CSL312 administration | — |
| Time to Maximum Plasma Concentration (Tmax) of CSL312 | Up to 28 days after CSL312 administration | — |
| Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-Last) of CSL312 | Up to 28 days after CSL312 administration | — |
| Terminal Half-life (T1/2) of CSL312 | Up to 28 days after CSL312 administration | — |
| Length of Hospital Stay | From randomization to Day 28 (+/- 2 days) | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo CSL312 diluent administered intravenously
Placebo: CSL312 diluent administered intravenously | 61 |
| CSL312 Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously | 63 |
| Total | 124 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Death | 11 | 10 |
| Overall Study | Failure to meet randomization requirement | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 3 |
| Overall Study | Non-compliance with study drug | 0 | 1 |
| Overall Study | Other | 1 | 1 |
| Overall Study | Randomized by mistake | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | Placebo | CSL312 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 28 Participants | 31 Participants | 59 Participants |
| Age, Categorical Between 18 and 65 years | 33 Participants | 32 Participants | 65 Participants |
| Age, Continuous | 62.2 years STANDARD_DEVIATION 12.74 | 62.7 years STANDARD_DEVIATION 14.61 | 62.5 years STANDARD_DEVIATION 13.67 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 14 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 48 Participants | 48 Participants | 96 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 7 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 9 Participants | 12 Participants |
| Race (NIH/OMB) White | 49 Participants | 44 Participants | 93 Participants |
| Region of Enrollment United States | 61 participants | 63 participants | 124 participants |
| Sex: Female, Male Female | 20 Participants | 30 Participants | 50 Participants |
| Sex: Female, Male Male | 41 Participants | 33 Participants | 74 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 11 / 61 | 11 / 63 |
| other Total, other adverse events | 21 / 59 | 18 / 58 |
| serious Total, serious adverse events | 19 / 59 | 20 / 58 |
Outcome results
Primary
The Percent of Participants With Tracheal Intubation or Death Prior to Tracheal Intubation
Time frame: From randomization to Day 28
Population: Intent-to-treat Analysis Set (ITT) comprises all subjects who were randomly assigned to treatment and who were assigned randomization numbers.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | The Percent of Participants With Tracheal Intubation or Death Prior to Tracheal Intubation | 26.2 percentage of participants |
| CSL312 | The Percent of Participants With Tracheal Intubation or Death Prior to Tracheal Intubation | 22.2 percentage of participants |
Secondary
Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-Last) of CSL312
Time frame: Up to 28 days after CSL312 administration
Population: PK
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-Last) of CSL312 | 15806.644 h*ug/mL | Standard Deviation 9393.6295 |
Secondary
Change From Baseline in SOFA Total Score
The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 (normal function) to 4 (most abnormal) with a total score ranging from 0 to 24. A high total SOFA score have been shown to be related to a worse outcome.
Time frame: From randomization to Day 28
Population: ITT. Participants with missing values were not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in SOFA Total Score | -1.0 score on a scale | Standard Deviation 1.77 |
| CSL312 | Change From Baseline in SOFA Total Score | -1.3 score on a scale | Standard Deviation 0.89 |
Secondary
Change From Baseline in the Individual Components of SOFA Score
The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 (normal function) to 4 (most abnormal) with a total score ranging from 0 to 24. A high total SOFA score have been shown to be related to a worse outcome.
Time frame: From randomization to Day 28
Population: ITT. Participants with missing values were not included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Individual Components of SOFA Score | Respiration Score | -0.6 score on a scale | Standard Deviation 1.32 |
| Placebo | Change From Baseline in the Individual Components of SOFA Score | Coagulation Score | -0.1 score on a scale | Standard Deviation 0.42 |
| Placebo | Change From Baseline in the Individual Components of SOFA Score | Liver Score | 0.0 score on a scale | Standard Deviation 0.22 |
| Placebo | Change From Baseline in the Individual Components of SOFA Score | Cardiovascular Score | 0.4 score on a scale | Standard Deviation 1.65 |
| Placebo | Change From Baseline in the Individual Components of SOFA Score | Central Nervous System Score | 0.0 score on a scale | Standard Deviation 0 |
| Placebo | Change From Baseline in the Individual Components of SOFA Score | Renal Score | 0.3 score on a scale | Standard Deviation 0.93 |
| CSL312 | Change From Baseline in the Individual Components of SOFA Score | Central Nervous System Score | 0.0 score on a scale | Standard Deviation 0.19 |
| CSL312 | Change From Baseline in the Individual Components of SOFA Score | Respiration Score | -1.2 score on a scale | Standard Deviation 1.16 |
| CSL312 | Change From Baseline in the Individual Components of SOFA Score | Cardiovascular Score | 0.5 score on a scale | Standard Deviation 1.35 |
| CSL312 | Change From Baseline in the Individual Components of SOFA Score | Coagulation Score | 0.4 score on a scale | Standard Deviation 1.12 |
| CSL312 | Change From Baseline in the Individual Components of SOFA Score | Renal Score | 0.5 score on a scale | Standard Deviation 1.1 |
| CSL312 | Change From Baseline in the Individual Components of SOFA Score | Liver Score | 0.0 score on a scale | Standard Deviation 0 |
Secondary
Length of Hospital Stay
Time frame: From randomization to Day 28 (+/- 2 days)
Population: ITT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Length of Hospital Stay | 7.00 Days |
| CSL312 | Length of Hospital Stay | 6.50 Days |
Secondary
Maximum Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score
The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 (normal function) to 4 (most abnormal) with a total score ranging from 0 to 24. A high total SOFA score have been shown to be related to a worse outcome.
Time frame: From randomization to Day 28
Population: ITT. Participants with missing values were not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score | 0.5 score on a scale | Standard Deviation 1.54 |
| CSL312 | Maximum Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score | 0.1 score on a scale | Standard Deviation 0.79 |
Secondary
Maximum Plasma Concentration (Cmax) of CSL312
Time frame: Up to 28 days after CSL312 administration
Population: The pharmacokinetic (PK) Analysis Set will comprise all subjects in the Safety Analysis Set who received any amount of CSL312 or placebo and have ≥ 1 blood sample available for CSL312 concentration measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Plasma Concentration (Cmax) of CSL312 | 147.335 ug/mL | Standard Deviation 77.1286 |
Secondary
Number of Participants Experiencing Adverse Events (AEs)
Time frame: Up to 28 days after CSL312 or placebo administration
Population: The Safety Analysis Set (SA) comprises all subjects in the ITT Analysis Set who receive any amount of CSL312 or placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants Experiencing Adverse Events (AEs) | 40 participants |
| CSL312 | Number of Participants Experiencing Adverse Events (AEs) | 35 participants |
Secondary
Number of Participants Experiencing Serious Adverse Events (SAEs)
Time frame: Up to 28 days after CSL312 or placebo administration
Population: SA
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants Experiencing Serious Adverse Events (SAEs) | 19 participants |
| CSL312 | Number of Participants Experiencing Serious Adverse Events (SAEs) | 20 participants |
Secondary
Number of Participants With ≥ 2-Point Improvement Compared to Baseline on National Institute of Allergy and Infectious Diseases (NIAID) Ordinal Scale
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Time frame: From randomization to Day 28
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With ≥ 2-Point Improvement Compared to Baseline on National Institute of Allergy and Infectious Diseases (NIAID) Ordinal Scale | 44 participants |
| CSL312 | Number of Participants With ≥ 2-Point Improvement Compared to Baseline on National Institute of Allergy and Infectious Diseases (NIAID) Ordinal Scale | 42 participants |
Secondary
Number of Participants With Adverse Events of Special Interest (AESIs)
Time frame: Up to 28 days after CSL312 or placebo administration
Population: SA
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Adverse Events of Special Interest (AESIs) | 6 participants |
| CSL312 | Number of Participants With Adverse Events of Special Interest (AESIs) | 5 participants |
Secondary
Number of Participants With Anti-CSL312 Antibodies
Time frame: Up to 28 days after CSL312 or placebo administration
Population: The pharmacodynamic (PD) Analysis Set will comprise all subjects in the Safety Analysis Set who received any amount of CSL312 or placebo and have ≥ 1 blood sample available for analysis of biomarkers.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Anti-CSL312 Antibodies | 1 participants |
| CSL312 | Number of Participants With Anti-CSL312 Antibodies | 0 participants |
Secondary
Number of Participants Within Each of the Categories of the NIAID at End of Study
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Time frame: Day 28
Population: ITT
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants Within Each of the Categories of the NIAID at End of Study | Hospitalized, on Non-invasive Ventilation or High-flow Oxygen Devices | 2 participants |
| Placebo | Number of Participants Within Each of the Categories of the NIAID at End of Study | Not Done | 5 participants |
| Placebo | Number of Participants Within Each of the Categories of the NIAID at End of Study | Hospitalized, on Invasive Mechanical Ventilation or ECMO | 2 participants |
| Placebo | Number of Participants Within Each of the Categories of the NIAID at End of Study | Hospitalized, Not Requiring Supplemental Oxygen - Requiring Ongoing Medical Care | 0 participants |
| Placebo | Number of Participants Within Each of the Categories of the NIAID at End of Study | Hospitalized, Requiring Supplemental Oxygen | 1 participants |
| Placebo | Number of Participants Within Each of the Categories of the NIAID at End of Study | Hospitalized, Not Requiring Supplemental Oxygen - no Longer Requiring Medical Care | 0 participants |
| Placebo | Number of Participants Within Each of the Categories of the NIAID at End of Study | Death | 11 participants |
| Placebo | Number of Participants Within Each of the Categories of the NIAID at End of Study | Not Hospitalized, Limitation on Activities and/or Requiring Home Oxygen | 14 participants |
| Placebo | Number of Participants Within Each of the Categories of the NIAID at End of Study | Missing | 1 participants |
| Placebo | Number of Participants Within Each of the Categories of the NIAID at End of Study | Not Hospitalized, no Limitations on Activities | 25 participants |
| CSL312 | Number of Participants Within Each of the Categories of the NIAID at End of Study | Missing | 6 participants |
| CSL312 | Number of Participants Within Each of the Categories of the NIAID at End of Study | Death | 11 participants |
| CSL312 | Number of Participants Within Each of the Categories of the NIAID at End of Study | Hospitalized, on Invasive Mechanical Ventilation or ECMO | 1 participants |
| CSL312 | Number of Participants Within Each of the Categories of the NIAID at End of Study | Hospitalized, on Non-invasive Ventilation or High-flow Oxygen Devices | 0 participants |
| CSL312 | Number of Participants Within Each of the Categories of the NIAID at End of Study | Hospitalized, Requiring Supplemental Oxygen | 2 participants |
| CSL312 | Number of Participants Within Each of the Categories of the NIAID at End of Study | Not Hospitalized, no Limitations on Activities | 26 participants |
| CSL312 | Number of Participants Within Each of the Categories of the NIAID at End of Study | Not Done | 6 participants |
| CSL312 | Number of Participants Within Each of the Categories of the NIAID at End of Study | Hospitalized, Not Requiring Supplemental Oxygen - Requiring Ongoing Medical Care | 0 participants |
| CSL312 | Number of Participants Within Each of the Categories of the NIAID at End of Study | Hospitalized, Not Requiring Supplemental Oxygen - no Longer Requiring Medical Care | 0 participants |
| CSL312 | Number of Participants Within Each of the Categories of the NIAID at End of Study | Not Hospitalized, Limitation on Activities and/or Requiring Home Oxygen | 11 participants |
Secondary
Percent of Participants Experiencing AEs
Time frame: Up to 28 days after CSL312 or placebo administration
Population: SA
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percent of Participants Experiencing AEs | 67.8 percentage of participants |
| CSL312 | Percent of Participants Experiencing AEs | 60.3 percentage of participants |
Secondary
Percent of Participants Experiencing SAEs
Time frame: Up to 28 days after CSL312 or placebo administration
Population: SA
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percent of Participants Experiencing SAEs | 32.2 percentage of participants |
| CSL312 | Percent of Participants Experiencing SAEs | 34.5 percentage of participants |
Secondary
Percent of Participants Requiring Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BiPAP)
Time frame: From randomization to Day 28
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percent of Participants Requiring Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BiPAP) | 16.4 percentage of participants |
| CSL312 | Percent of Participants Requiring Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BiPAP) | 19.0 percentage of participants |
Secondary
Percent of Participants Requiring Extracorporeal Membrane Oxygenation (ECMO)
None of the enrolled subjects required the use of ECMO during their participation in this study. Therefore, no data to report for this outcome measure.
Time frame: From randomization to Day 28
Population: ITT. None of the enrolled subjects required the use of ECMO during their participation in this study. Therefore, no data to report for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percent of Participants Requiring Extracorporeal Membrane Oxygenation (ECMO) | 0 percentage of participants |
| CSL312 | Percent of Participants Requiring Extracorporeal Membrane Oxygenation (ECMO) | 0 percentage of participants |
Secondary
Percent of Participants Requiring High-Flow Nasal Cannula (HFNC)
Time frame: From randomization to Day 28
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percent of Participants Requiring High-Flow Nasal Cannula (HFNC) | 18.0 percentage of participants |
| CSL312 | Percent of Participants Requiring High-Flow Nasal Cannula (HFNC) | 14.3 percentage of participants |
Secondary
Percent of Participants With ≥ 2-Point Improvement Compared to Baseline on NIAID
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Time frame: From randomization to Day 28
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percent of Participants With ≥ 2-Point Improvement Compared to Baseline on NIAID | 72.1 percentage of participants |
| CSL312 | Percent of Participants With ≥ 2-Point Improvement Compared to Baseline on NIAID | 66.7 percentage of participants |
Secondary
Percent of Participants With AESIs
Time frame: Up to 28 days after CSL312 or placebo administration
Population: SA
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percent of Participants With AESIs | 10.2 percentage of participants |
| CSL312 | Percent of Participants With AESIs | 8.6 percentage of participants |
Secondary
Percent of Participants With Death From All Causes
Time frame: From randomization to Day 28
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percent of Participants With Death From All Causes | 18.0 percentage of participants |
| CSL312 | Percent of Participants With Death From All Causes | 17.5 percentage of participants |
Secondary
Percent of Participants Within Each of the Categories of the NIAID at End of Study
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Time frame: Day 28
Population: ITT
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percent of Participants Within Each of the Categories of the NIAID at End of Study | Death | 18.0 percentage of participants |
| Placebo | Percent of Participants Within Each of the Categories of the NIAID at End of Study | Hospitalized, on Invasive Mechanical Ventilation or ECMO | 3.3 percentage of participants |
| Placebo | Percent of Participants Within Each of the Categories of the NIAID at End of Study | Hospitalized, on Non-invasive Ventilation or High-flow Oxygen Devices | 3.3 percentage of participants |
| Placebo | Percent of Participants Within Each of the Categories of the NIAID at End of Study | Hospitalized, Requiring Supplemental Oxygen | 1.6 percentage of participants |
| Placebo | Percent of Participants Within Each of the Categories of the NIAID at End of Study | Hospitalized, Not Requiring Supplemental Oxygen - Requiring Ongoing Medical Care | 0 percentage of participants |
| Placebo | Percent of Participants Within Each of the Categories of the NIAID at End of Study | Hospitalized, Not Requiring Supplemental Oxygen - no Longer Requiring Medical Care | 0 percentage of participants |
| Placebo | Percent of Participants Within Each of the Categories of the NIAID at End of Study | Not Hospitalized, Limitation on Activities and/or Requiring Home Oxygen | 23.0 percentage of participants |
| Placebo | Percent of Participants Within Each of the Categories of the NIAID at End of Study | Not Hospitalized, no Limitations on Activities | 41.0 percentage of participants |
| Placebo | Percent of Participants Within Each of the Categories of the NIAID at End of Study | Not Done | 8.2 percentage of participants |
| Placebo | Percent of Participants Within Each of the Categories of the NIAID at End of Study | Missing | 1.6 percentage of participants |
| CSL312 | Percent of Participants Within Each of the Categories of the NIAID at End of Study | Not Hospitalized, no Limitations on Activities | 41.3 percentage of participants |
| CSL312 | Percent of Participants Within Each of the Categories of the NIAID at End of Study | Death | 17.5 percentage of participants |
| CSL312 | Percent of Participants Within Each of the Categories of the NIAID at End of Study | Hospitalized, Not Requiring Supplemental Oxygen - no Longer Requiring Medical Care | 0 percentage of participants |
| CSL312 | Percent of Participants Within Each of the Categories of the NIAID at End of Study | Hospitalized, on Invasive Mechanical Ventilation or ECMO | 1.6 percentage of participants |
| CSL312 | Percent of Participants Within Each of the Categories of the NIAID at End of Study | Missing | 9.5 percentage of participants |
| CSL312 | Percent of Participants Within Each of the Categories of the NIAID at End of Study | Hospitalized, on Non-invasive Ventilation or High-flow Oxygen Devices | 0 percentage of participants |
| CSL312 | Percent of Participants Within Each of the Categories of the NIAID at End of Study | Not Hospitalized, Limitation on Activities and/or Requiring Home Oxygen | 17.5 percentage of participants |
| CSL312 | Percent of Participants Within Each of the Categories of the NIAID at End of Study | Hospitalized, Requiring Supplemental Oxygen | 3.2 percentage of participants |
| CSL312 | Percent of Participants Within Each of the Categories of the NIAID at End of Study | Not Done | 9.5 percentage of participants |
| CSL312 | Percent of Participants Within Each of the Categories of the NIAID at End of Study | Hospitalized, Not Requiring Supplemental Oxygen - Requiring Ongoing Medical Care | 0 percentage of participants |
Secondary
Percent of Participants With Tracheal Intubation
Time frame: From randomization to Day 28
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percent of Participants With Tracheal Intubation | 24.6 percentage of participants |
| CSL312 | Percent of Participants With Tracheal Intubation | 17.5 percentage of participants |
Secondary
Terminal Half-life (T1/2) of CSL312
Time frame: Up to 28 days after CSL312 administration
Population: PK. Participants with missing values were not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Terminal Half-life (T1/2) of CSL312 | 226.165 hours | Standard Deviation 102.669 |
Secondary
Time to Maximum Plasma Concentration (Tmax) of CSL312
Time frame: Up to 28 days after CSL312 administration
Population: PK
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Maximum Plasma Concentration (Tmax) of CSL312 | 0.667 hours |