Treatment With CSL312 in Adults With Coronavirus Disease 2019 (COVID-19)

• ClinicalTrials.gov Identifier: NCT04409509
• Recruitment Status: Completed
• First Posted: June 1, 2020
• Results First Posted: January 24, 2022
• Last Update Posted: January 24, 2022
• Sponsor: CSL Behring
• Information provided by (Responsible Party): CSL Behring

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Coronavirus Disease 2019 (COVID-19)
• Interventions: Biological: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody; Drug: Placebo
• Enrollment: 124

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Placebo	CSL312
Arm/Group Description	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
Period Title: Overall Study
Started	61	63
Completed	48	43
Not Completed	13	20
Reason Not Completed
Failure to meet randomization requirement	1	0
Adverse Event	0	1
Death	11	10
Non-compliance with study drug	0	1
Lost to Follow-up	0	3
Withdrawal by Subject	0	3
Randomized by mistake	0	1
Other	1	1

Baseline Characteristics

Arm/Group Title		Placebo	CSL312	Total
Arm/Group Description		CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously	Total of all reporting groups
Overall Number of Baseline Participants		61	63	124
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	61 participants	63 participants	124 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	33 54.1%	32 50.8%	65 52.4%
	>=65 years	28 45.9%	31 49.2%	59 47.6%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	61 participants	63 participants	124 participants
		62.2 (12.74)	62.7 (14.61)	62.5 (13.67)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	61 participants	63 participants	124 participants
	Female	20 32.8%	30 47.6%	50 40.3%
	Male	41 67.2%	33 52.4%	74 59.7%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	61 participants	63 participants	124 participants
	Hispanic or Latino	10 16.4%	14 22.2%	24 19.4%
	Not Hispanic or Latino	48 78.7%	48 76.2%	96 77.4%
	Unknown or Not Reported	3 4.9%	1 1.6%	4 3.2%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	61 participants	63 participants	124 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	2 3.3%	2 3.2%	4 3.2%
	Native Hawaiian or Other Pacific Islander	1 1.6%	0 0.0%	1 0.8%
	Black or African American	6 9.8%	7 11.1%	13 10.5%
	White	49 80.3%	44 69.8%	93 75.0%
	More than one race	0 0.0%	1 1.6%	1 0.8%
	Unknown or Not Reported	3 4.9%	9 14.3%	12 9.7%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	61 participants	63 participants	124 participants
		61	63	124

Outcome Measures

1. Primary Outcome

Title	The Percent of Participants With Tracheal Intubation or Death Prior to Tracheal Intubation
Description	[Not Specified]
Time Frame	From randomization to Day 28

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	CSL312
Arm/Group Description:	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
Overall Number of Participants Analyzed	61	63
Measure Type: Number; Unit of Measure: percentage of participants
	26.2	22.2

2. Secondary Outcome

Title	Percent of Participants With Death From All Causes
Description	[Not Specified]
Time Frame	From randomization to Day 28

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Placebo	CSL312
Arm/Group Description:	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
Overall Number of Participants Analyzed	61	63
Measure Type: Number; Unit of Measure: percentage of participants
	18.0	17.5

3. Secondary Outcome

Title	Percent of Participants With Tracheal Intubation
Description	[Not Specified]
Time Frame	From randomization to Day 28

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Placebo	CSL312
Arm/Group Description:	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
Overall Number of Participants Analyzed	61	63
Measure Type: Number; Unit of Measure: percentage of participants
	24.6	17.5

4. Secondary Outcome

Title	Number of Participants With ≥ 2-Point Improvement Compared to Baseline on National Institute of Allergy and Infectious Diseases (NIAID) Ordinal Scale
Description	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

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Placebo	CSL312
Arm/Group Description:	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
Overall Number of Participants Analyzed	61	63
Measure Type: Number; Unit of Measure: participants
	44	42

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Placebo	CSL312
Arm/Group Description:	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
Overall Number of Participants Analyzed	61	63
Measure Type: Number; Unit of Measure: percentage of participants
	72.1	66.7

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Placebo	CSL312
Arm/Group Description:	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
Overall Number of Participants Analyzed	61	63
Measure Type: Number; Unit of Measure: participants
Death	11	11
Hospitalized, on Invasive Mechanical Ventilation or ECMO	2	1
Hospitalized, on Non-invasive Ventilation or High-flow Oxygen Devices	2	0
Hospitalized, Requiring Supplemental Oxygen	1	2
Hospitalized, Not Requiring Supplemental Oxygen - Requiring Ongoing Medical Care	0	0
Hospitalized, Not Requiring Supplemental Oxygen - no Longer Requiring Medical Care	0	0
Not Hospitalized, Limitation on Activities and/or Requiring Home Oxygen	14	11
Not Hospitalized, no Limitations on Activities	25	26
Not Done	5	6
Missing	1	6

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Placebo	CSL312
Arm/Group Description:	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
Overall Number of Participants Analyzed	61	63
Measure Type: Number; Unit of Measure: percentage of participants
Death	18.0	17.5
Hospitalized, on Invasive Mechanical Ventilation or ECMO	3.3	1.6
Hospitalized, on Non-invasive Ventilation or High-flow Oxygen Devices	3.3	0
Hospitalized, Requiring Supplemental Oxygen	1.6	3.2
Hospitalized, Not Requiring Supplemental Oxygen - Requiring Ongoing Medical Care	0	0
Hospitalized, Not Requiring Supplemental Oxygen - no Longer Requiring Medical Care	0	0
Not Hospitalized, Limitation on Activities and/or Requiring Home Oxygen	23.0	17.5
Not Hospitalized, no Limitations on Activities	41.0	41.3
Not Done	8.2	9.5
Missing	1.6	9.5

8. Secondary Outcome

Title	Percent of Participants Requiring Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BiPAP)
Description	[Not Specified]
Time Frame	From randomization to Day 28

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Placebo	CSL312
Arm/Group Description:	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
Overall Number of Participants Analyzed	61	63
Measure Type: Number; Unit of Measure: percentage of participants
	16.4	19.0

9. Secondary Outcome

Title	Percent of Participants Requiring Extracorporeal Membrane Oxygenation (ECMO)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	CSL312
Arm/Group Description:	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
Overall Number of Participants Analyzed	61	63
Measure Type: Number; Unit of Measure: percentage of participants
	0	0

10. Secondary Outcome

Title	Percent of Participants Requiring High-Flow Nasal Cannula (HFNC)
Description	[Not Specified]
Time Frame	From randomization to Day 28

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Placebo	CSL312
Arm/Group Description:	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
Overall Number of Participants Analyzed	61	63
Measure Type: Number; Unit of Measure: percentage of participants
	18.0	14.3

11. Secondary Outcome

Title	Maximum Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	CSL312
Arm/Group Description:	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
Overall Number of Participants Analyzed	50	45
Mean (Standard Deviation); Unit of Measure: score on a scale
	0.5 (1.54)	0.1 (0.79)

12. Secondary Outcome

Title	Change From Baseline in SOFA Total Score
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	CSL312
Arm/Group Description:	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
Overall Number of Participants Analyzed	15	12
Mean (Standard Deviation); Unit of Measure: score on a scale
	-1.0 (1.77)	-1.3 (0.89)

13. Secondary Outcome

Title	Change From Baseline in the Individual Components of SOFA Score
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title		Placebo	CSL312
Arm/Group Description:		CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
Overall Number of Participants Analyzed		61	63
Mean (Standard Deviation); Unit of Measure: score on a scale
Respiration Score	Number Analyzed	34 participants	28 participants
		-0.6 (1.32)	-1.2 (1.16)
Coagulation Score	Number Analyzed	23 participants	19 participants
		-0.1 (0.42)	0.4 (1.12)
Liver Score	Number Analyzed	21 participants	17 participants
		0.0 (0.22)	0.0 (0.00)
Cardiovascular Score	Number Analyzed	35 participants	29 participants
		0.4 (1.65)	0.5 (1.35)
Central Nervous System Score	Number Analyzed	26 participants	27 participants
		0.0 (0.00)	0.0 (0.19)
Renal Score	Number Analyzed	23 participants	20 participants
		0.3 (0.93)	0.5 (1.10)

14. Secondary Outcome

Title	Length of Hospital Stay
Description	[Not Specified]
Time Frame	From randomization to Day 28 (+/- 2 days)

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Placebo	CSL312
Arm/Group Description:	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
Overall Number of Participants Analyzed	61	63
Median (Full Range); Unit of Measure: Days
	7.00; (0 to 29)	6.50; (0 to 28)

15. Secondary Outcome

Title	Number of Participants Experiencing Adverse Events (AEs)
Description	[Not Specified]
Time Frame	Up to 28 days after CSL312 or placebo administration

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	CSL312
Arm/Group Description:	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
Overall Number of Participants Analyzed	59	58
Measure Type: Number; Unit of Measure: participants
	40	35

16. Secondary Outcome

Title	Percent of Participants Experiencing AEs
Description	[Not Specified]
Time Frame	Up to 28 days after CSL312 or placebo administration

Outcome Measure Data

Analysis Population Description

SA

Arm/Group Title	Placebo	CSL312
Arm/Group Description:	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
Overall Number of Participants Analyzed	59	58
Measure Type: Number; Unit of Measure: percentage of participants
	67.8	60.3

17. Secondary Outcome

Title	Number of Participants Experiencing Serious Adverse Events (SAEs)
Description	[Not Specified]
Time Frame	Up to 28 days after CSL312 or placebo administration

Outcome Measure Data

Analysis Population Description

SA

Arm/Group Title	Placebo	CSL312
Arm/Group Description:	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
Overall Number of Participants Analyzed	59	58
Measure Type: Number; Unit of Measure: participants
	19	20

18. Secondary Outcome

Title	Percent of Participants Experiencing SAEs
Description	[Not Specified]
Time Frame	Up to 28 days after CSL312 or placebo administration

Outcome Measure Data

Analysis Population Description

SA

Arm/Group Title	Placebo	CSL312
Arm/Group Description:	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
Overall Number of Participants Analyzed	59	58
Measure Type: Number; Unit of Measure: percentage of participants
	32.2	34.5

19. Secondary Outcome

Title	Number of Participants With Adverse Events of Special Interest (AESIs)
Description	[Not Specified]
Time Frame	Up to 28 days after CSL312 or placebo administration

Outcome Measure Data

Analysis Population Description

SA

Arm/Group Title	Placebo	CSL312
Arm/Group Description:	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
Overall Number of Participants Analyzed	59	58
Measure Type: Number; Unit of Measure: participants
	6	5

20. Secondary Outcome

Title	Percent of Participants With AESIs
Description	[Not Specified]
Time Frame	Up to 28 days after CSL312 or placebo administration

Outcome Measure Data

Analysis Population Description

SA

Arm/Group Title	Placebo	CSL312
Arm/Group Description:	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
Overall Number of Participants Analyzed	59	58
Measure Type: Number; Unit of Measure: percentage of participants
	10.2	8.6

21. Secondary Outcome

Title	Number of Participants With Anti-CSL312 Antibodies
Description	[Not Specified]
Time Frame	Up to 28 days after CSL312 or placebo administration

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	CSL312
Arm/Group Description:	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
Overall Number of Participants Analyzed	59	58
Measure Type: Number; Unit of Measure: participants
	1	0

22. Secondary Outcome

Title	Maximum Plasma Concentration (Cmax) of CSL312
Description	[Not Specified]
Time Frame	Up to 28 days after CSL312 administration

Outcome Measure Data

Analysis Population Description

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/Group Title	CSL312
Arm/Group Description:	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
Overall Number of Participants Analyzed	57
Mean (Standard Deviation); Unit of Measure: ug/mL
	147.335 (77.1286)

23. Secondary Outcome

Title	Time to Maximum Plasma Concentration (Tmax) of CSL312
Description	[Not Specified]
Time Frame	Up to 28 days after CSL312 administration

Outcome Measure Data

Analysis Population Description

PK

Arm/Group Title	CSL312
Arm/Group Description:	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
Overall Number of Participants Analyzed	57
Median (Full Range); Unit of Measure: hours
	0.667; (0.28 to 139.97)

24. Secondary Outcome

Title	Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-Last) of CSL312
Description	[Not Specified]
Time Frame	Up to 28 days after CSL312 administration

Outcome Measure Data

Analysis Population Description

PK

Arm/Group Title	CSL312
Arm/Group Description:	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
Overall Number of Participants Analyzed	57
Mean (Standard Deviation); Unit of Measure: h*ug/mL
	15806.644 (9393.6295)

25. Secondary Outcome

Title	Terminal Half-life (T1/2) of CSL312
Description	[Not Specified]
Time Frame	Up to 28 days after CSL312 administration

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	CSL312
Arm/Group Description:	Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
Overall Number of Participants Analyzed	9
Mean (Standard Deviation); Unit of Measure: hours
	226.165 (102.6690)

Adverse Events

Time Frame	Up to 28 days per participant after CSL312 or placebo administration
Adverse Event Reporting Description	All-Cause mortality uses ITT set and treatment emergent adverse events uses the safety analysis set.
Arm/Group Title	Placebo		CSL312
Arm/Group Description	CSL312 diluent administered intravenously Placebo: CSL312 diluent administered intravenously		Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously Garadacimab, Factor XIIa Antagonist Monoclonal Antibody: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody administered intravenously
All-Cause Mortality
	Placebo		CSL312
	Affected / at Risk (%)		Affected / at Risk (%)
Total	11/61 (18.03%)		11/63 (17.46%)
Serious Adverse Events
	Placebo		CSL312
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/59 (32.20%)		20/58 (34.48%)
Blood and lymphatic system disorders
Anaemia † 1	1/59 (1.69%)	1	0/58 (0.00%)	0
Disseminated intravascular coagulation † 1	0/59 (0.00%)	0	1/58 (1.72%)	1
Thrombocytopenia † 1	1/59 (1.69%)	1	0/58 (0.00%)	0
Cardiac disorders
Cardiac arrest † 1	1/59 (1.69%)	1	3/58 (5.17%)	3
Sinus tachycardia † 1	0/59 (0.00%)	0	1/58 (1.72%)	1
Tachycardia † 1	0/59 (0.00%)	0	1/58 (1.72%)	1
General disorders
Asthenia † 1	1/59 (1.69%)	1	0/58 (0.00%)	0
Infections and infestations
Septic shock † 1	4/59 (6.78%)	4	1/58 (1.72%)	1
Pneumonia † 1	1/59 (1.69%)	1	1/58 (1.72%)	2
Sepsis † 1	2/59 (3.39%)	2	0/58 (0.00%)	0
Diverticulitis † 1	0/59 (0.00%)	0	1/58 (1.72%)	1
Enterobacter bacteraemia † 1	1/59 (1.69%)	1	0/58 (0.00%)	0
Enterobacter pneumonia † 1	1/59 (1.69%)	1	0/58 (0.00%)	0
Pneumonia escherichia † 1	1/59 (1.69%)	1	0/58 (0.00%)	0
Pneumonia streptococcal † 1	1/59 (1.69%)	1	0/58 (0.00%)	0
Injury, poisoning and procedural complications
Subdural haematoma † 1	1/59 (1.69%)	1	0/58 (0.00%)	0
Metabolism and nutrition disorders
Hypoglycaemia † 1	1/59 (1.69%)	1	0/58 (0.00%)	0
Nervous system disorders
Brain hypoxia † 1	0/59 (0.00%)	0	1/58 (1.72%)	1
Cerebellar infarction † 1	1/59 (1.69%)	1	0/58 (0.00%)	0
Cerebral infarction † 1	1/59 (1.69%)	1	0/58 (0.00%)	0
Haemorrhagic stroke † 1	1/59 (1.69%)	1	0/58 (0.00%)	0
Subarachnoid haemorrhage † 1	1/59 (1.69%)	1	0/58 (0.00%)	0
Psychiatric disorders
Mental status changes † 1	0/59 (0.00%)	0	1/58 (1.72%)	1
Renal and urinary disorders
Acute kidney injury † 1	2/59 (3.39%)	2	1/58 (1.72%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory failure † 1	7/59 (11.86%)	8	6/58 (10.34%)	6
Hypoxia † 1	1/59 (1.69%)	1	4/58 (6.90%)	5
Acute respiratory failure † 1	1/59 (1.69%)	1	4/58 (6.90%)	4
Pulmonary embolism † 1	2/59 (3.39%)	2	2/58 (3.45%)	3
Pneumothorax † 1	1/59 (1.69%)	1	1/58 (1.72%)	1
Acute respiratory distress syndrome † 1	1/59 (1.69%)	1	0/58 (0.00%)	0
Dyspnoea † 1	1/59 (1.69%)	1	0/58 (0.00%)	0
Epistaxis † 1	0/59 (0.00%)	0	1/58 (1.72%)	1
Vascular disorders
Deep vein thrombosis † 1	1/59 (1.69%)	1	3/58 (5.17%)	3
Hypotension † 1	3/59 (5.08%)	3	1/58 (1.72%)	1
Arterial thrombosis † 1	1/59 (1.69%)	1	0/58 (0.00%)	0
Peripheral artery thrombosis † 1	1/59 (1.69%)	1	0/58 (0.00%)	0
Peripheral ischaemia † 1	0/59 (0.00%)	0	1/58 (1.72%)	1
Venous thrombosis † 1	1/59 (1.69%)	1	0/58 (0.00%)	0
1 Term from vocabulary, MedDRA 23.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo		CSL312
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/59 (35.59%)		18/58 (31.03%)
Cardiac disorders
Atrial fibrillation † 1	5/59 (8.47%)	5	2/58 (3.45%)	2
Bradycardia † 1	0/59 (0.00%)	0	3/58 (5.17%)	3
Gastrointestinal disorders
Constipation † 1	3/59 (5.08%)	3	0/58 (0.00%)	0
Infections and infestations
Septic shock † 1	2/59 (3.39%)	2	3/58 (5.17%)	3
Investigations
Transaminases increased † 1	4/59 (6.78%)	4	1/58 (1.72%)	1
Fibrin D dimer increased † 1	3/59 (5.08%)	3	1/58 (1.72%)	1
Metabolism and nutrition disorders
Hyperglycaemia † 1	5/59 (8.47%)	5	5/58 (8.62%)	5
Hyperkalaemia † 1	3/59 (5.08%)	3	2/58 (3.45%)	2
Hypokalaemia † 1	3/59 (5.08%)	3	2/58 (3.45%)	2
Psychiatric disorders
Anxiety † 1	2/59 (3.39%)	2	3/58 (5.17%)	3
Renal and urinary disorders
Acute kidney injury † 1	6/59 (10.17%)	6	0/58 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	3/59 (5.08%)	3	2/58 (3.45%)	2
Vascular disorders
Hypotension † 1	6/59 (10.17%)	6	2/58 (3.45%)	2
1 Term from vocabulary, MedDRA 23.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Study Director
• Organization: CSL Behring
• Phone: 610-878-4000
• EMail: clinicaltrials@cslbehring.com

• Responsible Party: CSL Behring
• ClinicalTrials.gov Identifier: NCT04409509
• Other Study ID Numbers: CSL312_COVID-19
• First Submitted: May 28, 2020
• First Posted: June 1, 2020
• Results First Submitted: December 23, 2021
• Results First Posted: January 24, 2022
• Last Update Posted: January 24, 2022