Treatment With CSL312 in Adults With Coronavirus Disease... | NCT04409509

Label	Type	Description	Intervention Names
CSL312	Experimental	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously	Biological: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody
Placebo	Placebo Comparator	CSL312 diluent administered intravenously	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Garadacimab, Factor XIIa Antagonist Monoclonal Antibody	Biological	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously	CSL312

Measure	Description	Time Frame
The Percent of Participants With Tracheal Intubation or Death Prior to Tracheal Intubation		From randomization to Day 28

Measure	Description	Time Frame
Percent of Participants With Death From All Causes		From randomization to Day 28
Percent of Participants With Tracheal Intubation		From randomization to Day 28

Eligibility Module

Eligibility Criteria

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

Name	Affiliation	Role
Study Director	CSL Behring	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Nova Clinical Research, LLC		Bradenton	Florida	34209	United States
Theia Clinical Research, LLC

PubMed Identifier	Type	Citation	Retractions
37000214	Derived	Papi A, Stapleton RD, Shore PM, Bica MA, Chen Y, Larbig M, Welte T. Efficacy and Safety of Garadacimab in Combination with Standard of Care Treatment in Patients with Severe COVID-19. Lung. 2023 Apr;201(2):159-170. doi: 10.1007/s00408-023-00615-9. Epub 2023 Mar 31.

ID	Title	Description
FG000	Placebo	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously
FG001	CSL312	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Sep 16, 2020	Dec 23, 2021

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

The Percent of Participants With Tracheal Intubation or Death Prior to Tracheal Intubation

Intent-to-treat Analysis Set (ITT) comprises all subjects who were randomly assigned to treatment and who were assigned randomization numbers.

Posted

Number

percentage of participants

From randomization to Day 28

ID	Title	Description
OG000	Placebo	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously
OG001	CSL312	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously

Units	Counts
Participants	OG00061 OG00163

Title

Denominators

Categories

Title	Measurements
	OG00026.2 OG00122.2

Secondary

Percent of Participants With Death From All Causes

ITT

Posted

Number

percentage of participants

From randomization to Day 28

ID	Title	Description
OG000	Placebo	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously
OG001	CSL312	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously

Units	Counts
Participants	OG000

Secondary

Percent of Participants With Tracheal Intubation

ITT

Posted

Number

percentage of participants

From randomization to Day 28

ID	Title	Description
OG000	Placebo	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously
OG001	CSL312	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously

Units	Counts
Participants	OG000

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.

ITT

Posted

Number

participants

From randomization to Day 28

ID	Title	Description
OG000	Placebo	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously
OG001	CSL312	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously

Secondary

Percent of Participants With ≥ 2-Point Improvement Compared to Baseline on NIAID

ITT

Posted

Number

percentage of participants

From randomization to Day 28

ID	Title	Description
OG000	Placebo	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously
OG001	CSL312	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously

Secondary

Number of Participants Within Each of the Categories of the NIAID at End of Study

ITT

Posted

Number

participants

Day 28

ID	Title	Description
OG000	Placebo	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously
OG001	CSL312	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously

Units

Secondary

Percent of Participants Within Each of the Categories of the NIAID at End of Study

ITT

Posted

Number

percentage of participants

Day 28

ID	Title	Description
OG000	Placebo	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously
OG001	CSL312	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously

Secondary

Percent of Participants Requiring Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BiPAP)

ITT

Posted

Number

percentage of participants

From randomization to Day 28

ID	Title	Description
OG000	Placebo	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously
OG001	CSL312	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously

Units	Counts
Participants	OG000

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.

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.

Posted

Number

percentage of participants

From randomization to Day 28

ID	Title	Description
OG000	Placebo	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously
OG001	CSL312	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously

Units	Counts
Participants	OG000

Secondary

Percent of Participants Requiring High-Flow Nasal Cannula (HFNC)

ITT

Posted

Number

percentage of participants

From randomization to Day 28

ID	Title	Description
OG000	Placebo	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously
OG001	CSL312	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously

Units	Counts
Participants	OG000

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.

ITT. Participants with missing values were not included in the analysis.

Posted

Mean

Standard Deviation

score on a scale

From randomization to Day 28

ID	Title	Description
OG000	Placebo	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously
OG001	CSL312	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously

Units	Counts
Participants

Secondary

Change From Baseline in SOFA Total Score

ITT. Participants with missing values were not included in the analysis.

Posted

Mean

Standard Deviation

score on a scale

From randomization to Day 28

ID	Title	Description
OG000	Placebo	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously
OG001	CSL312	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously

Units	Counts
Participants	OG000

Secondary

Change From Baseline in the Individual Components of SOFA Score

ITT. Participants with missing values were not included in the analysis.

Posted

Mean

Standard Deviation

score on a scale

From randomization to Day 28

ID	Title	Description
OG000	Placebo	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously
OG001	CSL312	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously

Units	Counts
Participants

Secondary

Length of Hospital Stay

ITT

Posted

Median

Full Range

Days

From randomization to Day 28 (+/- 2 days)

ID	Title	Description
OG000	Placebo	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously
OG001	CSL312	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously

Units	Counts
Participants	OG000

Secondary

Number of Participants Experiencing Adverse Events (AEs)

The Safety Analysis Set (SA) comprises all subjects in the ITT Analysis Set who receive any amount of CSL312 or placebo.

Posted

Number

participants

Up to 28 days after CSL312 or placebo administration

ID	Title	Description
OG000	Placebo	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously
OG001	CSL312	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously

Units	Counts
Participants	OG000

Secondary

Percent of Participants Experiencing AEs

Posted

Number

percentage of participants

Up to 28 days after CSL312 or placebo administration

ID	Title	Description
OG000	Placebo	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously
OG001	CSL312	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously

Units	Counts
Participants	OG000

Secondary

Number of Participants Experiencing Serious Adverse Events (SAEs)

Posted

Number

participants

Up to 28 days after CSL312 or placebo administration

ID	Title	Description
OG000	Placebo	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously
OG001	CSL312	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously

Units	Counts
Participants	OG000

Secondary

Percent of Participants Experiencing SAEs

Posted

Number

percentage of participants

Up to 28 days after CSL312 or placebo administration

ID	Title	Description
OG000	Placebo	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously
OG001	CSL312	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously

Units	Counts
Participants	OG000

Secondary

Number of Participants With Adverse Events of Special Interest (AESIs)

Posted

Number

participants

Up to 28 days after CSL312 or placebo administration

ID	Title	Description
OG000	Placebo	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously
OG001	CSL312	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously

Units	Counts
Participants	OG000

Secondary

Percent of Participants With AESIs

Posted

Number

percentage of participants

Up to 28 days after CSL312 or placebo administration

ID	Title	Description
OG000	Placebo	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously
OG001	CSL312	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously

Units	Counts
Participants	OG000

Secondary

Number of Participants With Anti-CSL312 Antibodies

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.

Posted

Number

participants

Up to 28 days after CSL312 or placebo administration

ID	Title	Description
OG000	Placebo	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously
OG001	CSL312	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously

Units	Counts
Participants	OG000

Secondary

Maximum Plasma Concentration (Cmax) of CSL312

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.

Posted

Mean

Standard Deviation

ug/mL

Up to 28 days after CSL312 administration

ID	Title	Description
OG000	CSL312	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously

Units	Counts
Participants	OG000

Secondary

Time to Maximum Plasma Concentration (Tmax) of CSL312

Posted

Median

Full Range

hours

Up to 28 days after CSL312 administration

ID	Title	Description
OG000	CSL312	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously

Units	Counts
Participants	OG00057

Secondary

Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-Last) of CSL312

Posted

Mean

Standard Deviation

h*ug/mL

Up to 28 days after CSL312 administration

ID	Title	Description
OG000	CSL312	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously

Units	Counts
Participants	OG00057

Secondary

Terminal Half-life (T1/2) of CSL312

PK. Participants with missing values were not included in the analysis.

Posted

Mean

Standard Deviation

hours

Up to 28 days after CSL312 administration

ID	Title	Description
OG000	CSL312	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously

Units	Counts
Participants	OG0009

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0008 events7 affected59 at risk EG0016 events6 affected58 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected59 at risk EG0015 events4 affected58 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected59 at risk EG0014 events4 affected58 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0002 events2 affected59 at risk EG0013 events2 affected58 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected59 at risk EG0011 events1 affected58 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected59 at risk EG0013 events3 affected58 at risk
Hypotension	Vascular disorders	MedDRA 23.1	Systematic Assessment	EG0003 events3 affected59 at risk EG0011 events1 affected58 at risk
Arterial thrombosis	Vascular disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk
Peripheral artery thrombosis	Vascular disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk
Peripheral ischaemia	Vascular disorders	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk
Venous thrombosis	Vascular disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk
Septic shock	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0004 events4 affected59 at risk EG0011 events1 affected58 at risk
Pneumonia	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected59 at risk EG0012 events1 affected58 at risk
Sepsis	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0002 events2 affected59 at risk EG0010 events0 affected58 at risk
Diverticulitis	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk
Enterobacter bacteraemia	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk
Enterobacter pneumonia	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk
Pneumonia escherichia	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk
Pneumonia streptococcal	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk
Cardiac arrest	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected59 at risk EG0013 events3 affected58 at risk
Sinus tachycardia	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk
Tachycardia	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk
Brain hypoxia	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk
Cerebellar infarction	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk
Cerebral infarction	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk
Haemorrhagic stroke	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk
Subarachnoid haemorrhage	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk
Disseminated intravascular coagulation	Blood and lymphatic system disorders	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 23.1	Systematic Assessment	EG0002 events2 affected59 at risk EG0011 events1 affected58 at risk
Asthenia	General disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk
Mental status changes	Psychiatric disorders	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk

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	Title	Description
BG000	Placebo	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously
BG001	CSL312	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously	11	61	19	59	21	59
EG001	CSL312	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously	11	63	20	58	18	58

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG0005 events5 affected59 at risk EG0015 events5 affected58 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG0003 events3 affected59 at risk EG0012 events2 affected58 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG0003 events3 affected59 at risk EG0012 events2 affected58 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0005 events5 affected59 at risk EG0012 events2 affected58 at risk
Bradycardia	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0000 events0 affected59 at risk EG0013 events3 affected58 at risk
Transaminases increased	Investigations	MedDRA 23.1	Systematic Assessment	EG0004 events4 affected59 at risk EG0011 events1 affected58 at risk
Fibrin D dimer increased	Investigations	MedDRA 23.1	Systematic Assessment	EG0003 events3 affected59 at risk EG0011 events1 affected58 at risk
Hypotension	Vascular disorders	MedDRA 23.1	Systematic Assessment	EG0006 events6 affected59 at risk EG0012 events2 affected58 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 23.1	Systematic Assessment	EG0006 events6 affected59 at risk EG0010 events0 affected58 at risk
Septic shock	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0002 events2 affected59 at risk EG0013 events3 affected58 at risk
Anxiety	Psychiatric disorders	MedDRA 23.1	Systematic Assessment	EG0002 events2 affected59 at risk EG0013 events3 affected58 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 23.1	Systematic Assessment	EG0003 events3 affected59 at risk EG0012 events2 affected58 at risk
Constipation	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0003 events3 affected59 at risk EG0010 events0 affected58 at risk