A Study to Investigate CSL312 in Subjects With Hereditary Angioedema (HAE)

• ClinicalTrials.gov Identifier: NCT03712228
• Recruitment Status: Completed
• First Posted: October 19, 2018
• Results First Posted: November 8, 2022
• Last Update Posted: November 8, 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: Prevention
• Condition: Hereditary Angioedema
• Interventions: Biological: Factor XIIa antagonist monoclonal antibody; Drug: Placebo
• Enrollment: 44

Participant Flow

Recruitment Details

Pre-assignment Details

Treatment Period 1 participants were assigned to 1 of 5 treatment arms. Treatment period 2 participants that completed Treatment Period 1 were assigned to either CSL312 (medium) or CSL312 (high) and could be up-titrated from CSL312 (medium) to CSL312 (med/high), if necessary. They were down-titrated from CSL312 (high) to CSL312 (medium). Only 2 subjects from the CSL312 (FXII/PLG HAE) arm were treated with CSL312 in Treatment Period 2.

Arm/Group Title	Placebo	CSL312 (Low)	CSL312 (Med)	CSL312 (High)	CSL312 (Med/High)	CSL312 (FXII/PLG HAE)
Arm/Group Description	Subjects with C1-INH HAE (Hereditary angioedema with C1-esterase inhibitor deficiency) receiving buffer only Placebo: Buffer without active ingredient	Subjects with C1-INH HAE (Hereditary angioedema with C1-esterase inhibitor deficiency) receiving low dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE (Hereditary angioedema with C1-esterase inhibitor deficiency) receiving medium dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE (Hereditary angioedema with C1-esterase inhibitor deficiency) receiving high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE (Hereditary angioedema with C1-esterase inhibitor deficiency) receiving medium/high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with FXII/PLG HAE (Hereditary Angioedema with Normal C1-esterase Inhibitor and Factor XII or Plasminogen Gene Mutation) receiving high dose CSL312
Period Title: Treatment Period 1
Started	8	9	8	7	6	6
Completed	8	9	8	7	6	5
Not Completed	0	0	0	0	0	1
Reason Not Completed
Lack of Efficacy	0	0	0	0	0	1
Period Title: Treatment Period 2
Started	0	0	20	18	0	2
Completed	0	0	20	16	0	2
Not Completed	0	0	0	2	0	0
Reason Not Completed
Pregnancy	0	0	0	1	0	0
Withdrawal by Subject	0	0	0	1	0	0

Baseline Characteristics

Arm/Group Title		Placebo	CSL312 (Low)	CSL312 (Med)	CSL312 (High)	CSL312 (Med/High)	CSL312 (FXII/PLG HAE)	Total
Arm/Group Description		Subjects with C1-INH HAE (Hereditary angioedema with C1-esterase inhibitor deficiency) receiving buffer only Placebo: Buffer without active ingredient	Subjects with C1-INH HAE (Hereditary angioedema with C1-esterase inhibitor deficiency)receiving low dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE (Hereditary angioedema with C1-esterase inhibitor deficiency) receiving medium dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE (Hereditary angioedema with C1-esterase inhibitor deficiency)receiving high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE (Hereditary angioedema with C1-esterase inhibitor deficiency) receiving medium/high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with FXII/PLG HAE (Hereditary Angioedema with Normal C1-esterase Inhibitor and Factor XII or Plasminogen Gene Mutation) receiving high dose CSL312	Total of all reporting groups
Overall Number of Baseline Participants		8	9	8	7	6	6	44
Baseline Analysis Population Description		The Intent-to-Treat (ITT) population consisted of all subjects who provided informed consent, underwent any study screening procedure, and who were assigned to treatment in Treatment Period 1 or to treatment in Treatment Period 2, regardless of whether they received investigational product.
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	8 participants	9 participants	8 participants	7 participants	6 participants	6 participants	44 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	8 100.0%	9 100.0%	8 100.0%	6 85.7%	6 100.0%	6 100.0%	43 97.7%
	>=65 years	0 0.0%	0 0.0%	0 0.0%	1 14.3%	0 0.0%	0 0.0%	1 2.3%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	8 participants	9 participants	8 participants	7 participants	6 participants	6 participants	44 participants
	Female	4 50.0%	7 77.8%	2 25.0%	5 71.4%	3 50.0%	6 100.0%	27 61.4%
	Male	4 50.0%	2 22.2%	6 75.0%	2 28.6%	3 50.0%	0 0.0%	17 38.6%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	8 participants	9 participants	8 participants	7 participants	6 participants	6 participants	44 participants
	Hispanic or Latino	1 12.5%	0 0.0%	0 0.0%	0 0.0%	1 16.7%	0 0.0%	2 4.5%
	Not Hispanic or Latino	7 87.5%	9 100.0%	8 100.0%	7 100.0%	5 83.3%	6 100.0%	42 95.5%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	8 participants	9 participants	8 participants	7 participants	6 participants	6 participants	44 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%	2 28.6%	1 16.7%	0 0.0%	3 6.8%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 16.7%	0 0.0%	1 2.3%
	White	7 87.5%	9 100.0%	8 100.0%	5 71.4%	4 66.7%	6 100.0%	39 88.6%
	More than one race	1 12.5%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 2.3%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	8 participants	9 participants	8 participants	7 participants	6 participants	6 participants	44 participants
Canada		1	3	2	1	0	0	7
United States		4	2	0	2	2	1	11
Israel		0	2	2	1	2	2	9
Germany		3	2	4	3	2	3	17

Outcome Measures

1. Primary Outcome

Title	The Mean Time Normalized Number of HAE Attacks Per Month in Subjects With C1-INH HAE During Treatment Period 1
Description	The time-normalized number of HAE attacks per month during Treatment Period 1 for a subject was calculated as the (number of HAE attacks / length of subject's evaluation period in days) * 30.4375
Time Frame	13 weeks

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat (ITT) population consisted of all subjects who provided informed consent, underwent any study screening procedure, and who were assigned to treatment in Treatment Period 1 or to treatment in Treatment Period 2, regardless of whether they received investigational product.

Arm/Group Title	Placebo	CSL312 (Low)	CSL312 (Med)	CSL312 (High)	CSL312 (Med/High)
Arm/Group Description:	Subjects with C1-INH HAE receiving buffer only Placebo: Buffer without active ingredient	Subjects with C1-INH HAE receiving low dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium/high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
Overall Number of Participants Analyzed	8	9	8	7	6
Mean (Standard Deviation); Unit of Measure: Number of HAE attacks per month
	4.24 (1.801)	0.48 (1.057)	0.05 (0.127)	0.35 (0.407)	0.14 (0.222)

2. Secondary Outcome

Title	The Number of Responder Subjects With C1-INH HAE During Treatment Period 1
Description	Response is defined as a ≥ 50% relative reduction in the time-normalized number of HAE attacks (per month) during Treatment Period 1 compared to each subject's time-normalized number of HAE attacks (per month) during the Run-in Period
Time Frame	13 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Placebo	CSL312 (Low)	CSL312 (Med)	CSL312 (High)	CSL312 (Med/High)
Arm/Group Description:	Subjects with C1-INH HAE receiving buffer only Placebo: Buffer without active ingredient	Subjects with C1-INH HAE receiving low dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium/high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
Overall Number of Participants Analyzed	8	9	8	7	6
Measure Type: Number; Unit of Measure: Number of participants
	0	9	8	6	6

3. Secondary Outcome

Title	The Percentage of Responder Subjects With C1-INH HAE During Treatment Period 1
Description	Response is defined as a ≥ 50% relative reduction in the time-normalized number of HAE attacks (per month) during Treatment Period 1 compared to each subject's time-normalized number of HAE attacks (per month) during the Run-in Period.
Time Frame	13 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Placebo	CSL312 (Low)	CSL312 (Med)	CSL312 (High)	CSL312 (Med/High)
Arm/Group Description:	Subjects with C1-INH HAE receiving buffer only Placebo: Buffer without active ingredient	Subjects with C1-INH HAE receiving low dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium/high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
Overall Number of Participants Analyzed	8	9	8	7	6
Measure Type: Number; Unit of Measure: percentage of participants
	0	100.0	100.0	85.7	100.0

4. Secondary Outcome

Title	The Number of HAE Attack-free Subjects With C1-INH HAE During Treatment Period 1
Description	[Not Specified]
Time Frame	13 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Placebo	CSL312 (Low)	CSL312 (Med)	CSL312 (High)	CSL312 (Med/High)
Arm/Group Description:	Subjects with C1-INH HAE receiving buffer only Placebo: Buffer without active ingredient	Subjects with C1-INH HAE receiving low dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium/high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
Overall Number of Participants Analyzed	8	9	8	7	6
Measure Type: Number; Unit of Measure: Number of participants
	0	5	7	3	4

5. Secondary Outcome

Title	The Percentage of HAE Attack-free Subjects With C1-INH HAE During Treatment Period 1
Description	[Not Specified]
Time Frame	13 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Placebo	CSL312 (Low)	CSL312 (Med)	CSL312 (High)	CSL312 (Med/High)
Arm/Group Description:	Subjects with C1-INH HAE receiving buffer only Placebo: Buffer without active ingredient	Subjects with C1-INH HAE receiving low dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium/high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
Overall Number of Participants Analyzed	8	9	8	7	6
Measure Type: Number; Unit of Measure: percentage of participants
	0	55.6	87.5	42.9	66.7

6. Secondary Outcome

Title	The Number of Mild, Moderate or Severe HAE Attacks in Subjects With C1-INH HAE During Treatment Period 1
Description	[Not Specified]
Time Frame	13 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Placebo	CSL312 (Low)	CSL312 (Med)	CSL312 (High)	CSL312 (Med/High)
Arm/Group Description:	Subjects with C1-INH HAE receiving buffer only Placebo: Buffer without active ingredient	Subjects with C1-INH HAE receiving low dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium/high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
Overall Number of Participants Analyzed	8	9	8	7	6
Overall Number of Units Analyzed; Type of Units Analyzed: Total Number of HAE Attacks	95	12	1	7	2
Measure Type: Number; Unit of Measure: Number of HAE attacks
Mild	32	3	0	2	2
Moderate	43	9	1	4	0
Severe	20	0	0	1	0

7. Secondary Outcome

Title	The Percentage of Mild, Moderate or Severe HAE Attacks in Subjects With C1-INH HAE During Treatment Period 1
Description	[Not Specified]
Time Frame	13 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Placebo	CSL312 (Low)	CSL312 (Med)	CSL312 (High)	CSL312 (Med/High)
Arm/Group Description:	Subjects with C1-INH HAE receiving buffer only Placebo: Buffer without active ingredient	Subjects with C1-INH HAE receiving low dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium/high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
Overall Number of Participants Analyzed	8	9	8	7	6
Overall Number of Units Analyzed; Type of Units Analyzed: Total Number of HAE Attacks	95	12	1	7	2
Measure Type: Number; Unit of Measure: percentage of HAE attacks
Mild	33.7	25.0	0	28.6	100.0
Moderate	45.3	75.0	100.0	57.1	0
Severe	21.1	0	0	14.3	0

8. Secondary Outcome

Title	The Mean Time-normalized Number of Mild, Moderate or Severe HAE Attacks Per Month in Subjects With C1-INH HAE During Treatment Period 1
Description	The time-normalized number of HAE attacks per month during Treatment Period 1 for a subject was calculated as the (number of HAE attacks / length of subject's evaluation period in days) * 30.4375
Time Frame	13 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Placebo	CSL312 (Low)	CSL312 (Med)	CSL312 (High)	CSL312 (Med/High)
Arm/Group Description:	Subjects with C1-INH HAE receiving buffer only Placebo: Buffer without active ingredient	Subjects with C1-INH HAE receiving low dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium/high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
Overall Number of Participants Analyzed	8	9	8	7	6
Overall Number of Units Analyzed; Type of Units Analyzed: Total number of HAE attacks	95	12	1	7	2
Mean (Standard Deviation); Unit of Measure: Number of HAE attacks per month
Mild	1.42 (1.395)	0.12 (0.177)	0.0 (0.000)	0.10 (0.168)	0.14 (0.222)
Moderate	1.93 (1.403)	0.36 (1.087)	0.05 (0.127)	0.20 (0.347)	0.0 (0.000)
Severe	0.89 (1.365)	0.0 (0.000)	0.0 (0.000)	0.05 (0.136)	0.0 (0.000)

9. Secondary Outcome

Title	The Number of Subjects With at Least One (1) HAE Attack Treated With On-demand HAE Medication, in Subjects With C1-INH HAE During Treatment Period 1
Description	[Not Specified]
Time Frame	13 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Placebo	CSL312 (Low)	CSL312 (Med)	CSL312 (High)	CSL312 (Med/High)
Arm/Group Description:	Subjects with C1-INH HAE receiving buffer only Placebo: Buffer without active ingredient	Subjects with C1-INH HAE receiving low dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium/high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
Overall Number of Participants Analyzed	8	9	8	7	6
Measure Type: Number; Unit of Measure: Number of participants
	8	3	1	2	0

10. Secondary Outcome

Title	The Percentage of Subjects With at Least One (1) HAE Attack Treated With On-demand HAE Medication, in Subjects With C1-INH HAE During Treatment Period 1
Description	[Not Specified]
Time Frame	13 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Placebo	CSL312 (Low)	CSL312 (Med)	CSL312 (High)	CSL312 (Med/High)
Arm/Group Description:	Subjects with C1-INH HAE receiving buffer only Placebo: Buffer without active ingredient	Subjects with C1-INH HAE receiving low dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium/high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
Overall Number of Participants Analyzed	8	9	8	7	6
Measure Type: Number; Unit of Measure: percentage of participants
	100.0	33.3	12.5	28.6	0

11. Secondary Outcome

Title	Maximum Concentration (Cmax) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
Description	[Not Specified]
Time Frame	13 weeks

Outcome Measure Data

Analysis Population Description

The pharmacokinetic (PK) population consisted of all subjects in the Safety population for whom at least 1 measurable concentration of CSL312 was reported.

Arm/Group Title	Placebo	CSL312 (Low)	CSL312 (Med)	CSL312 (High)	CSL312 (Med/High)
Arm/Group Description:	Subjects with C1-INH HAE receiving buffer only Placebo: Buffer without active ingredient	Subjects with C1-INH HAE receiving low dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium/high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
Overall Number of Participants Analyzed	0	9	8	7	0
Mean (Standard Deviation); Unit of Measure: ug/mL
		10.6 (6.09)	15.9 (5.22)	56.4 (15.9)

12. Secondary Outcome

Title	Area Under the Concentration-time Curve in 1 Dosing Interval (AUC0-tau) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
Description	[Not Specified]
Time Frame	13 weeks

Outcome Measure Data

Analysis Population Description

PK

Arm/Group Title	Placebo	CSL312 (Low)	CSL312 (Med)	CSL312 (High)	CSL312 (Med/High)
Arm/Group Description:	Subjects with C1-INH HAE receiving buffer only Placebo: Buffer without active ingredient	Subjects with C1-INH HAE receiving low dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium/high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
Overall Number of Participants Analyzed	0	9	8	7	0
Mean (Standard Deviation); Unit of Measure: h*μg/mL
		4507 (2424)	7166 (2410)	26514 (8151)

13. Secondary Outcome

Title	Time of Maximum Concentration (Tmax) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
Description	[Not Specified]
Time Frame	13 weeks

Outcome Measure Data

Analysis Population Description

PK

Arm/Group Title	Placebo	CSL312 (Low)	CSL312 (Med)	CSL312 (High)	CSL312 (Med/High)
Arm/Group Description:	Subjects with C1-INH HAE receiving buffer only Placebo: Buffer without active ingredient	Subjects with C1-INH HAE receiving low dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium/high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
Overall Number of Participants Analyzed	0	9	8	7	0
Median (Full Range); Unit of Measure: hours
		143.38; (45.4 to 196)	165.51; (116 to 218)	165.63; (72.4 to 188)

14. Secondary Outcome

Title	Terminal Elimination Half-life (T1/2) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
Description	[Not Specified]
Time Frame	13 weeks

Outcome Measure Data

Analysis Population Description

PK

Arm/Group Title	Placebo	CSL312 (Low)	CSL312 (Med)	CSL312 (High)	CSL312 (Med/High)
Arm/Group Description:	Subjects with C1-INH HAE receiving buffer only Placebo: Buffer without active ingredient	Subjects with C1-INH HAE receiving low dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium/high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
Overall Number of Participants Analyzed	0	7	7	5	0
Mean (Standard Deviation); Unit of Measure: hours
		411.7 (96.97)	394.0 (85.64)	443.5 (44.00)

15. Secondary Outcome

Title	Clearance (CL/F) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
Description	[Not Specified]
Time Frame	13 weeks

Outcome Measure Data

Analysis Population Description

PK

Arm/Group Title	Placebo	CSL312 (Low)	CSL312 (Med)	CSL312 (High)	CSL312 (Med/High)
Arm/Group Description:	Subjects with C1-INH HAE receiving buffer only Placebo: Buffer without active ingredient	Subjects with C1-INH HAE receiving low dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium/high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
Overall Number of Participants Analyzed	0	9	8	7	0
Mean (Standard Deviation); Unit of Measure: L/hour
		0.0198 (0.0079)	0.0303 (0.0084)	0.0246 (0.0079)

16. Secondary Outcome

Title	Volume of Distribution During the Elimination Phase (Vz/F) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
Description	[Not Specified]
Time Frame	13 weeks

Outcome Measure Data

Analysis Population Description

PK

Arm/Group Title	Placebo	CSL312 (Low)	CSL312 (Med)	CSL312 (High)	CSL312 (Med/High)
Arm/Group Description:	Subjects with C1-INH HAE receiving buffer only Placebo: Buffer without active ingredient	Subjects with C1-INH HAE receiving low dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium/high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
Overall Number of Participants Analyzed	0	7	7	5	0
Mean (Standard Deviation); Unit of Measure: Liters
		10.6 (5.10)	17.0 (4.78)	17.1 (6.67)

17. Secondary Outcome

Title	The Number of Subjects With C1-INH HAE With Adverse Events (AEs), Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESI), Injection Site Reactions (ISRs), Binding Antibodies to CSL312 During Treatment Period 1
Description	Adverse events of special interest is defined as anaphylaxis, thromboembolic events, and bleeding events.
Time Frame	13 weeks

Outcome Measure Data

Analysis Population Description

The Safety population (SP) consisted of all subjects who provided informed consent, were assigned to treatment in Treatment Period 1 or to treatment in Treatment Period 2 and received at least 1 dose or partial dose of investigational product and was based on the actual treatment received.

Arm/Group Title	Placebo	CSL312 (Low)	CSL312 (Med)	CSL312 (High)	CSL312 (Med/High)
Arm/Group Description:	Subjects with C1-INH HAE receiving buffer only Placebo: Buffer without active ingredient	Subjects with C1-INH HAE receiving low dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use	Subjects with C1-INH HAE receiving medium/high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
Overall Number of Participants Analyzed	8	9	8	7	6
Measure Type: Number; Unit of Measure: Number of participants
AEs	7	7	7	7	4
SAEs	0	0	0	0	0
AESI	1	0	0	0	0
ISRs	2	1	1	4	2
Binding Antibodies to CSL312	1	0	0	0	0

Adverse Events

Time Frame	Approximately 129 weeks per participant
Adverse Event Reporting Description	Adverse events were collected for both Treatment Periods 1 (up to 13 weeks) and 2 (up to 44 weeks + up to 13 weeks follow-up). Adverse events will be reported by Treatment Period.
Arm/Group Title	Placebo		CSL312 (Low)		CSL312 (Med)		CSL312 (High)		CSL312 (Med/High)		CSL312 (Med-Period 2)		CSL312 (Med/High-Period 2)		CSL312 (High-Period 2)		CSL312 (FXII/PLG HAE-Period 1)		CSL312 (FXII/PLG HAE-Period 2)
Arm/Group Description	Subjects with C1-INH HAE receiving buffer only Placebo: Buffer without active ingredient		Subjects with C1-INH HAE receiving low dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use		Subjects with C1-INH HAE receiving medium dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use		Subjects with C1-INH HAE receiving high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use		Subjects with C1-INH HAE receiving medium/high dose CSL312 Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use		Subjects with C1-INH HAE receiving medium dose CSL312		Subjects with C1-INH HAE receiving medium/high dose CSL312		Subjects with C1-INH HAE receiving high dose CSL312		Subjects with FXII/PLG HAE (Hereditary Angioedema with Normal C1-esterase Inhibitor and Factor XII or Plasminogen Gene Mutation) receiving high dose CSL312		Subjects with FXII/PLG HAE (Hereditary Angioedema with Normal C1-esterase Inhibitor and Factor XII or Plasminogen Gene Mutation) receiving high dose CSL312
All-Cause Mortality
	Placebo		CSL312 (Low)		CSL312 (Med)		CSL312 (High)		CSL312 (Med/High)		CSL312 (Med-Period 2)		CSL312 (Med/High-Period 2)		CSL312 (High-Period 2)		CSL312 (FXII/PLG HAE-Period 1)		CSL312 (FXII/PLG HAE-Period 2)
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/8 (0.00%)		0/9 (0.00%)		0/8 (0.00%)		0/7 (0.00%)		0/6 (0.00%)		0/36 (0.00%)		0/3 (0.00%)		0/18 (0.00%)		0/6 (0.00%)		0/2 (0.00%)
Serious Adverse Events
	Placebo		CSL312 (Low)		CSL312 (Med)		CSL312 (High)		CSL312 (Med/High)		CSL312 (Med-Period 2)		CSL312 (Med/High-Period 2)		CSL312 (High-Period 2)		CSL312 (FXII/PLG HAE-Period 1)		CSL312 (FXII/PLG HAE-Period 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0.00%)		0/9 (0.00%)		0/8 (0.00%)		0/7 (0.00%)		0/6 (0.00%)		1/36 (2.78%)		0/3 (0.00%)		1/18 (5.56%)		1/6 (16.67%)		0/2 (0.00%)
Congenital, familial and genetic disorders
Hereditary angioedema †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	1/6 (16.67%)	1	0/2 (0.00%)	0
Gastrointestinal disorders
Diverticular perforation †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/36 (2.78%)	1	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Asthma †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo		CSL312 (Low)		CSL312 (Med)		CSL312 (High)		CSL312 (Med/High)		CSL312 (Med-Period 2)		CSL312 (Med/High-Period 2)		CSL312 (High-Period 2)		CSL312 (FXII/PLG HAE-Period 1)		CSL312 (FXII/PLG HAE-Period 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/8 (87.50%)		7/9 (77.78%)		7/8 (87.50%)		7/7 (100.00%)		4/6 (66.67%)		25/36 (69.44%)		2/3 (66.67%)		17/18 (94.44%)		1/6 (16.67%)		2/2 (100.00%)
Blood and lymphatic system disorders
Lymphopenia †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Cardiac disorders
Palpitations †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Ear and labyrinth disorders
Vestibular disorder †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Eye disorders
Photopsia †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Gastrointestinal disorders
Nausea †	2/8 (25.00%)	2	0/9 (0.00%)	0	0/8 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	1/36 (2.78%)	3	0/3 (0.00%)	0	2/18 (11.11%)	3	1/6 (16.67%)	1	0/2 (0.00%)	0
Abdominal pain †	0/8 (0.00%)	0	1/9 (11.11%)	1	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	5/36 (13.89%)	7	1/3 (33.33%)	1	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Abdominal pain upper †	0/8 (0.00%)	0	0/9 (0.00%)	0	1/8 (12.50%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	2/36 (5.56%)	2	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Gastritis †	0/8 (0.00%)	0	0/9 (0.00%)	0	1/8 (12.50%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	2/18 (11.11%)	2	0/6 (0.00%)	0	0/2 (0.00%)	0
Gastrooesophageal reflux disease †	0/8 (0.00%)	0	0/9 (0.00%)	0	1/8 (12.50%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Toothache †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	2/36 (5.56%)	2	0/3 (0.00%)	0	2/18 (11.11%)	2	0/6 (0.00%)	0	0/2 (0.00%)	0
Dyspepsia †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	2/36 (5.56%)	2	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	1/2 (50.00%)	1
Inguinal hernia †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	2/36 (5.56%)	2	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Dental caries †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
General disorders
Injection site erythema †	2/8 (25.00%)	2	0/9 (0.00%)	0	1/8 (12.50%)	1	1/7 (14.29%)	2	0/6 (0.00%)	0	1/36 (2.78%)	1	0/3 (0.00%)	0	3/18 (16.67%)	6	0/6 (0.00%)	0	0/2 (0.00%)	0
Injection site pain †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	3/7 (42.86%)	3	1/6 (16.67%)	4	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	2	0/6 (0.00%)	0	0/2 (0.00%)	0
Chest discomfort †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	2/7 (28.57%)	2	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	2	0/6 (0.00%)	0	0/2 (0.00%)	0
Injection site pruritus †	1/8 (12.50%)	1	0/9 (0.00%)	0	1/8 (12.50%)	2	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Pyrexia †	0/8 (0.00%)	0	0/9 (0.00%)	0	1/8 (12.50%)	1	1/7 (14.29%)	1	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	1/2 (50.00%)	1
Fatigue †	0/8 (0.00%)	0	0/9 (0.00%)	0	1/8 (12.50%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	1/36 (2.78%)	1	0/3 (0.00%)	0	2/18 (11.11%)	4	0/6 (0.00%)	0	0/2 (0.00%)	0
Injection site reaction †	0/8 (0.00%)	0	1/9 (11.11%)	1	0/8 (0.00%)	0	0/7 (0.00%)	0	1/6 (16.67%)	1	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	1/6 (16.67%)	1	0/2 (0.00%)	0
Injection site swelling †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Injection site urticaria †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	1/6 (16.67%)	2	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Chest pain †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Chills †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Facial pain †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Malaise †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	1/2 (50.00%)	1
Immune system disorders
Food allergy †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Infections and infestations
Upper respiratory tract infection †	2/8 (25.00%)	2	2/9 (22.22%)	2	3/8 (37.50%)	3	0/7 (0.00%)	0	0/6 (0.00%)	0	4/36 (11.11%)	4	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Nasopharyngitis †	0/8 (0.00%)	0	0/9 (0.00%)	0	2/8 (25.00%)	2	1/7 (14.29%)	2	0/6 (0.00%)	0	3/36 (8.33%)	6	0/3 (0.00%)	0	3/18 (16.67%)	4	0/6 (0.00%)	0	0/2 (0.00%)	0
Abscess limb †	0/8 (0.00%)	0	1/9 (11.11%)	1	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Cellulitis †	1/8 (12.50%)	1	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Gastroenteritis †	0/8 (0.00%)	0	1/9 (11.11%)	1	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Gingivitis †	1/8 (12.50%)	1	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Nasal herpes †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Oral herpes †	0/8 (0.00%)	0	0/9 (0.00%)	0	1/8 (12.50%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	1/36 (2.78%)	5	0/3 (0.00%)	0	1/18 (5.56%)	4	0/6 (0.00%)	0	0/2 (0.00%)	0
Pharyngitis †	0/8 (0.00%)	0	1/9 (11.11%)	1	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Tonsillitis †	0/8 (0.00%)	0	0/9 (0.00%)	0	1/8 (12.50%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Urinary tract infection †	1/8 (12.50%)	1	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	2/36 (5.56%)	4	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	1/2 (50.00%)	2
Sinusitis †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	2/36 (5.56%)	2	0/3 (0.00%)	0	2/18 (11.11%)	2	0/6 (0.00%)	0	0/2 (0.00%)	0
Cystitis †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/36 (2.78%)	1	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Hordeolum †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	2/36 (5.56%)	2	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Pneumonia †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/36 (2.78%)	1	1/3 (33.33%)	1	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Vulvovaginal mycotic infection †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/36 (2.78%)	1	1/3 (33.33%)	1	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Bronchitis †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
COVID-19 †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	2/2 (100.00%)	5
Herpes zoster †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	1/2 (50.00%)	1
Influenza †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	1/2 (50.00%)	1
Injury, poisoning and procedural complications
Contusion †	0/8 (0.00%)	0	1/9 (11.11%)	1	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	2/36 (5.56%)	3	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Muscle strain †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Vascular access site bruising †	1/8 (12.50%)	1	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Ligament sprain †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/36 (2.78%)	2	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Limb injury †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Skin laceration †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Investigations
SARS-CoV-2 test positive †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/36 (2.78%)	1	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Glycosylated haemoglobin increased †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Musculoskeletal and connective tissue disorders
Back pain †	1/8 (12.50%)	1	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	2/36 (5.56%)	3	0/3 (0.00%)	0	2/18 (11.11%)	2	0/6 (0.00%)	0	0/2 (0.00%)	0
Myalgia †	1/8 (12.50%)	1	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	1/2 (50.00%)	1
Patellofemoral pain syndrome †	0/8 (0.00%)	0	1/9 (11.11%)	1	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Plantar fascial fibromatosis †	0/8 (0.00%)	0	1/9 (11.11%)	1	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Arthralgia †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	1/6 (16.67%)	1	3/36 (8.33%)	3	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Muscular weakness †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	1/6 (16.67%)	1	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Pain in extremity †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/36 (2.78%)	1	0/3 (0.00%)	0	4/18 (22.22%)	4	0/6 (0.00%)	0	0/2 (0.00%)	0
Rotator cuff syndrome †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	3/36 (8.33%)	4	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Torticollis †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	2/36 (5.56%)	2	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Bone swelling †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Intervertebral disc protrusion †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Limb discomfort †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Nervous system disorders
Headache †	1/8 (12.50%)	1	0/9 (0.00%)	0	1/8 (12.50%)	1	2/7 (28.57%)	3	2/6 (33.33%)	5	6/36 (16.67%)	12	0/3 (0.00%)	0	4/18 (22.22%)	4	0/6 (0.00%)	0	1/2 (50.00%)	1
Dizziness †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	1/7 (14.29%)	2	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	1/2 (50.00%)	1
Nerve compression †	1/8 (12.50%)	1	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Sciatica †	0/8 (0.00%)	0	0/9 (0.00%)	0	1/8 (12.50%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Paraesthesia †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/36 (2.78%)	1	0/3 (0.00%)	0	1/18 (5.56%)	3	0/6 (0.00%)	0	0/2 (0.00%)	0
Anosmia †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Pregnancy, puerperium and perinatal conditions
Pregnancy †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/36 (2.78%)	1	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Psychiatric disorders
Initial insomnia †	0/8 (0.00%)	0	0/9 (0.00%)	0	1/8 (12.50%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Insomnia †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Anxiety †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	2/18 (11.11%)	4	0/6 (0.00%)	0	0/2 (0.00%)	0
Renal and urinary disorders
Renal pain †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Nephrolithiasis †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Ureterolithiasis †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Dysuria †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	1/2 (50.00%)	1
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain †	0/8 (0.00%)	0	0/9 (0.00%)	0	1/8 (12.50%)	1	1/7 (14.29%)	2	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Throat tightness †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Cough †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	1/6 (16.67%)	1	2/36 (5.56%)	2	0/3 (0.00%)	0	3/18 (16.67%)	3	0/6 (0.00%)	0	0/2 (0.00%)	0
Dyspnoea †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Dyspnoea at rest †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Epistaxis †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Hyperventilation †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Productive cough †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Pulmonary congestion †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Rhinorrhoea †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Skin and subcutaneous tissue disorders
Rash †	0/8 (0.00%)	0	0/9 (0.00%)	0	1/8 (12.50%)	2	2/7 (28.57%)	2	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Urticaria †	0/8 (0.00%)	0	1/9 (11.11%)	2	0/8 (0.00%)	0	1/7 (14.29%)	2	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Dermatitis †	0/8 (0.00%)	0	1/9 (11.11%)	1	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Ingrowing nail †	0/8 (0.00%)	0	0/9 (0.00%)	0	1/8 (12.50%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Polymorphic light eruption †	1/8 (12.50%)	1	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Erythema †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/36 (2.78%)	1	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Psoriasis †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Eczema †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	1/2 (50.00%)	1
Social circumstances
Pregnancy of partner †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	2/36 (5.56%)	2	0/3 (0.00%)	0	0/18 (0.00%)	0	0/6 (0.00%)	0	0/2 (0.00%)	0
Vascular disorders
Hot flush †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
Hypertension †	0/8 (0.00%)	0	0/9 (0.00%)	0	0/8 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/36 (0.00%)	0	0/3 (0.00%)	0	1/18 (5.56%)	1	0/6 (0.00%)	0	0/2 (0.00%)	0
† 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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Beard N, Frese M, Smertina E, Mere P, Katelaris C, Mills K. Interventions for the long-term prevention of hereditary angioedema attacks. Cochrane Database Syst Rev. 2022 Nov 3;11(11):CD013403. doi: 10.1002/14651858.CD013403.pub2.

Craig T, Magerl M, Levy DS, Reshef A, Lumry WR, Martinez-Saguer I, Jacobs JS, Yang WH, Ritchie B, Aygoren-Pursun E, Keith PK, Busse P, Feuersenger H, Pawaskar D, Jacobs I, Pragst I, Doyle MK. Prophylactic use of an anti-activated factor XII monoclonal antibody, garadacimab, for patients with C1-esterase inhibitor-deficient hereditary angioedema: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. 2022 Mar 5;399(10328):945-955. doi: 10.1016/S0140-6736(21)02225-X. Epub 2022 Feb 24.

• Responsible Party: CSL Behring
• ClinicalTrials.gov Identifier: NCT03712228
• Other Study ID Numbers: CSL312_2001; 2018-000605-24 ( EudraCT Number )
• First Submitted: October 17, 2018
• First Posted: October 19, 2018
• Results First Submitted: October 13, 2022
• Results First Posted: November 8, 2022
• Last Update Posted: November 8, 2022