A Study to Investigate CSL312 in Subjects With Hereditary... | NCT03712228 | Trialant
NCT03712228
Sponsor
CSL Behring
Status
Completed
Last Update Posted
Nov 8, 2022Actual
Enrollment
44Actual
Phase
Phase 2
Conditions
Hereditary Angioedema
Interventions
Factor XIIa antagonist monoclonal antibody
Placebo
Countries
United States
Australia
Canada
Germany
Israel
Protocol Section
Identification Module
NCT ID
NCT03712228
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
CSL312_2001
Secondary IDs
ID
Type
Description
Link
2018-000605-24
EudraCT Number
Brief Title
A Study to Investigate CSL312 in Subjects With Hereditary Angioedema (HAE)
Official Title
A Multicenter, Randomized, Placebo-controlled, Parallel-arm Study to Investigate the Efficacy, Pharmacokinetics, and Safety of CSL312 in Subjects With Hereditary Angioedema
Acronym
Not provided
Organization
CSL BehringINDUSTRY
Status Module
Record Verification Date
Oct 2022
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Oct 29, 2018Actual
Primary Completion Date
Oct 15, 2021Actual
Completion Date
Oct 15, 2021Actual
First Submitted Date
Oct 17, 2018
First Submission Date that Met QC Criteria
Oct 17, 2018
First Posted Date
Oct 19, 2018Actual
Results Waived
Not provided
Results First Submitted Date
Oct 13, 2022
Results First Submitted that Met QC Criteria
Oct 13, 2022
Results First Posted Date
Nov 8, 2022Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Oct 13, 2022
Last Update Posted Date
Nov 8, 2022Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
CSL BehringINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This is a multicenter, randomized, placebo-controlled, parallel-arm, phase 2 study to investigate the clinical efficacy, pharmacokinetics, and safety of CSL312 as prophylaxis to prevent attacks in subjects with HAE.
Detailed Description
Not provided
Conditions Module
Conditions
Hereditary Angioedema
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
44Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Placebo
Placebo Comparator
Subjects with C1-INH HAE receiving buffer only
Drug: Placebo
CSL312 (low)
Active Comparator
Subjects with C1-INH HAE receiving low dose CSL312
Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
CSL312 (high)
CSL312 (low)
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
The Mean Time Normalized Number of HAE Attacks Per Month in Subjects With C1-INH HAE During Treatment Period 1
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
13 weeks
Secondary Outcomes
Measure
Description
Time Frame
The Number of Responder Subjects With C1-INH HAE During Treatment Period 1
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
13 weeks
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Male or female
Aged ≥ 18 to ≤ 65 years
A diagnosis of C1-INH HAE or FXII/PLG HAE;
For subjects with C1-INH HAE: ≥ 4 HAE attacks over a consecutive 2-month period during the 3 months before Screening, as documented in the subject's medical record.
Exclusion Criteria:
History of clinically significant arterial or venous thrombosis, or current clinically significant prothrombotic risk
History of an uncontrolled, abnormal bleeding event due to a coagulopathy, or a current clinically significant coagulopathy or clinically significant risks for bleeding events
Craig TJ, Guilarte M, Li HH, Anderson J, Martinez Saguer I, Jacobs JS, Tachdjian R, Farkas H, Yang WH, Ohsawa I, Hakl R, Pollen M, Pragst I, Lawo JP, Shetty H, Nenci C, Magerl M. Long-Term Integrated Safety and Efficacy of Garadacimab for Hereditary Angioedema Prophylaxis. Adv Ther. 2026 Jun 10. doi: 10.1007/s12325-026-03628-x. Online ahead of print.
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.
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Placebo
Subjects with C1-INH HAE (Hereditary angioedema with C1-esterase inhibitor deficiency) receiving buffer only
Placebo: Buffer without active ingredient
FG001
CSL312 (Low)
Periods
Title
Milestones
Reasons Not Completed
Treatment Period 1
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Mar 20, 2020
Oct 13, 2022
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
No data available
No data is available for this block.
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Subjects are assigned to 1 of 2 or more groups in parallel for the duration of the study
The Percentage of Responder Subjects With C1-INH HAE During Treatment Period 1
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.
13 weeks
The Number of HAE Attack-free Subjects With C1-INH HAE During Treatment Period 1
13 weeks
The Percentage of HAE Attack-free Subjects With C1-INH HAE During Treatment Period 1
13 weeks
The Number of Mild, Moderate or Severe HAE Attacks in Subjects With C1-INH HAE During Treatment Period 1
13 weeks
The Percentage of Mild, Moderate or Severe HAE Attacks in Subjects With C1-INH HAE During Treatment Period 1
13 weeks
The Mean Time-normalized Number of Mild, Moderate or Severe HAE Attacks Per Month in Subjects With C1-INH HAE During Treatment Period 1
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
13 weeks
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
13 weeks
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
13 weeks
Maximum Concentration (Cmax) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
13 weeks
Area Under the Concentration-time Curve in 1 Dosing Interval (AUC0-tau) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
13 weeks
Time of Maximum Concentration (Tmax) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
13 weeks
Terminal Elimination Half-life (T1/2) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
13 weeks
Clearance (CL/F) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
13 weeks
Volume of Distribution During the Elimination Phase (Vz/F) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
13 weeks
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
Adverse events of special interest is defined as anaphylaxis, thromboembolic events, and bleeding events.
13 weeks
Walnut Creek
California
94598
United States
Immunoe Health Centers
Centennial
Colorado
80112
United States
Institute for Asthma and Allergy
Chevy Chase
Maryland
20815
United States
The Mount Sinai Hospital
New York
New York
10029
United States
Pennsylvania State University
Hershey
Pennsylvania
17033
United States
AARA Research Center
Dallas
Texas
75231
United States
Campbelltown Hospital
Campbelltown
New South Wales
2560
Australia
University of Alberta
Edmonton
Alberta
T6G 2B7
Canada
Allergy and Clinical Immunology McMaster University
Hamilton
Ontario
L8S 4K1
Canada
Ottawa Allergy Research Corp
Ottawa
Ontario
K1G 6C6
Canada
Charité Universitätsmedizin Berlin
Berlin
10117
Germany
Universitätsklinikum Frankfurt Goethe-Universität
Frankfurt
60590
Germany
Hautklinik und Poliklinik der Universitätsklinik Mainz
Mainz
55131
Germany
HZRM Hämophilie Zentrum Rhein Main GmbH
Mörfelden-Walldorf
64546
Germany
Barzilai University Medical Center
Ashkelon
7830604
Israel
Derived
Craig TJ, Levy DS, Reshef A, Lumry WR, Martinez-Saguer I, Jacobs JS, Yang WH, Ritchie B, Aygoren-Pursun E, Keith PK, Busse P, Feuersenger H, Alexandru Bica M, Jacobs I, Pragst I, Magerl M. Garadacimab for hereditary angioedema attack prevention: long-term efficacy, quality of life, and safety data from a phase 2, randomised, open-label extension study. Lancet Haematol. 2024 Jun;11(6):e436-e447. doi: 10.1016/S2352-3026(24)00081-4. Epub 2024 May 3.
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.
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
FG002
CSL312 (Med)
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
FG003
CSL312 (High)
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
FG004
CSL312 (Med/High)
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
FG005
CSL312 (FXII/PLG HAE)
Subjects with FXII/PLG HAE (Hereditary Angioedema with Normal C1-esterase Inhibitor and Factor XII or Plasminogen Gene Mutation) receiving high dose CSL312
FG0008 subjects
FG0019 subjects
FG0028 subjects
FG0037 subjects
FG0046 subjects
FG0056 subjects
COMPLETED
FG0008 subjects
FG0019 subjects
FG0028 subjects
FG0037 subjects
FG0046 subjects
FG0055 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0051 subjects
Type
Comment
Reasons
Lack of Efficacy
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0051 subjects
Treatment Period 2
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG00220 subjects
FG00318 subjects
FG0040 subjects
FG0052 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG00220 subjects
FG00316 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0032 subjects
FG004
Type
Comment
Reasons
Pregnancy
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
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.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Placebo
Subjects with C1-INH HAE (Hereditary angioedema with C1-esterase inhibitor deficiency) receiving buffer only
Placebo: Buffer without active ingredient
BG001
CSL312 (Low)
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
BG002
CSL312 (Med)
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
BG003
CSL312 (High)
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
BG004
CSL312 (Med/High)
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
BG005
CSL312 (FXII/PLG HAE)
Subjects with FXII/PLG HAE (Hereditary Angioedema with Normal C1-esterase Inhibitor and Factor XII or Plasminogen Gene Mutation) receiving high dose CSL312
BG006
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0008
BG0019
BG0028
BG0037
BG0046
BG0056
BG00644
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Categorical
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
<=18 years
BG0000
BG0010
BG0020
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0004
BG0017
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0001
BG0010
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Region of Enrollment
Number
participants
Title
Denominators
Categories
Canada
Title
Measurements
BG0001
BG0013
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
The Mean Time Normalized Number of HAE Attacks Per Month in Subjects With C1-INH HAE During Treatment Period 1
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
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.
Posted
Mean
Standard Deviation
Number of HAE attacks per month
13 weeks
ID
Title
Description
OG000
Placebo
Subjects with C1-INH HAE receiving buffer only
Placebo: Buffer without active ingredient
OG001
CSL312 (Low)
Subjects with C1-INH HAE receiving low dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG002
CSL312 (Med)
Subjects with C1-INH HAE receiving medium dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG003
CSL312 (High)
Subjects with C1-INH HAE receiving high dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG004
CSL312 (Med/High)
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
Units
Counts
Participants
OG0008
OG0019
OG0028
OG003
Title
Denominators
Categories
Title
Measurements
OG0004.24± 1.801
OG0010.48± 1.057
OG0020.05± 0.127
OG003
Secondary
The Number of Responder Subjects With C1-INH HAE During Treatment Period 1
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
ITT
Posted
Number
Number of participants
13 weeks
ID
Title
Description
OG000
Placebo
Subjects with C1-INH HAE receiving buffer only
Placebo: Buffer without active ingredient
OG001
CSL312 (Low)
Subjects with C1-INH HAE receiving low dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG002
CSL312 (Med)
Subjects with C1-INH HAE receiving medium dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG003
CSL312 (High)
Subjects with C1-INH HAE receiving high dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
Secondary
The Percentage of Responder Subjects With C1-INH HAE During Treatment Period 1
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.
ITT
Posted
Number
percentage of participants
13 weeks
ID
Title
Description
OG000
Placebo
Subjects with C1-INH HAE receiving buffer only
Placebo: Buffer without active ingredient
OG001
CSL312 (Low)
Subjects with C1-INH HAE receiving low dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG002
CSL312 (Med)
Subjects with C1-INH HAE receiving medium dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG003
CSL312 (High)
Subjects with C1-INH HAE receiving high dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
Secondary
The Number of HAE Attack-free Subjects With C1-INH HAE During Treatment Period 1
ITT
Posted
Number
Number of participants
13 weeks
ID
Title
Description
OG000
Placebo
Subjects with C1-INH HAE receiving buffer only
Placebo: Buffer without active ingredient
OG001
CSL312 (Low)
Subjects with C1-INH HAE receiving low dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG002
CSL312 (Med)
Subjects with C1-INH HAE receiving medium dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG003
CSL312 (High)
Subjects with C1-INH HAE receiving high dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG004
Secondary
The Percentage of HAE Attack-free Subjects With C1-INH HAE During Treatment Period 1
ITT
Posted
Number
percentage of participants
13 weeks
ID
Title
Description
OG000
Placebo
Subjects with C1-INH HAE receiving buffer only
Placebo: Buffer without active ingredient
OG001
CSL312 (Low)
Subjects with C1-INH HAE receiving low dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG002
CSL312 (Med)
Subjects with C1-INH HAE receiving medium dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG003
CSL312 (High)
Subjects with C1-INH HAE receiving high dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG004
Secondary
The Number of Mild, Moderate or Severe HAE Attacks in Subjects With C1-INH HAE During Treatment Period 1
ITT
Posted
Number
Number of HAE attacks
13 weeks
Total Number of HAE Attacks
Total Number of HAE Attacks
ID
Title
Description
OG000
Placebo
Subjects with C1-INH HAE receiving buffer only
Placebo: Buffer without active ingredient
OG001
CSL312 (Low)
Subjects with C1-INH HAE receiving low dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG002
CSL312 (Med)
Subjects with C1-INH HAE receiving medium dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG003
CSL312 (High)
Subjects with C1-INH HAE receiving high dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
Secondary
The Percentage of Mild, Moderate or Severe HAE Attacks in Subjects With C1-INH HAE During Treatment Period 1
ITT
Posted
Number
percentage of HAE attacks
13 weeks
Total Number of HAE Attacks
Total Number of HAE Attacks
ID
Title
Description
OG000
Placebo
Subjects with C1-INH HAE receiving buffer only
Placebo: Buffer without active ingredient
OG001
CSL312 (Low)
Subjects with C1-INH HAE receiving low dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG002
CSL312 (Med)
Subjects with C1-INH HAE receiving medium dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG003
CSL312 (High)
Subjects with C1-INH HAE receiving high dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
Secondary
The Mean Time-normalized Number of Mild, Moderate or Severe HAE Attacks Per Month in Subjects With C1-INH HAE During Treatment Period 1
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
ITT
Posted
Mean
Standard Deviation
Number of HAE attacks per month
13 weeks
Total number of HAE attacks
Total number of HAE attacks
ID
Title
Description
OG000
Placebo
Subjects with C1-INH HAE receiving buffer only
Placebo: Buffer without active ingredient
OG001
CSL312 (Low)
Subjects with C1-INH HAE receiving low dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG002
CSL312 (Med)
Subjects with C1-INH HAE receiving medium dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG003
CSL312 (High)
Secondary
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
ITT
Posted
Number
Number of participants
13 weeks
ID
Title
Description
OG000
Placebo
Subjects with C1-INH HAE receiving buffer only
Placebo: Buffer without active ingredient
OG001
CSL312 (Low)
Subjects with C1-INH HAE receiving low dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG002
CSL312 (Med)
Subjects with C1-INH HAE receiving medium dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG003
CSL312 (High)
Subjects with C1-INH HAE receiving high dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
Secondary
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
ITT
Posted
Number
percentage of participants
13 weeks
ID
Title
Description
OG000
Placebo
Subjects with C1-INH HAE receiving buffer only
Placebo: Buffer without active ingredient
OG001
CSL312 (Low)
Subjects with C1-INH HAE receiving low dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG002
CSL312 (Med)
Subjects with C1-INH HAE receiving medium dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG003
CSL312 (High)
Subjects with C1-INH HAE receiving high dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
Secondary
Maximum Concentration (Cmax) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
The pharmacokinetic (PK) population consisted of all subjects in the Safety population for whom at least 1 measurable concentration of CSL312 was reported.
Posted
Mean
Standard Deviation
ug/mL
13 weeks
ID
Title
Description
OG000
Placebo
Subjects with C1-INH HAE receiving buffer only
Placebo: Buffer without active ingredient
OG001
CSL312 (Low)
Subjects with C1-INH HAE receiving low dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG002
CSL312 (Med)
Subjects with C1-INH HAE receiving medium dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG003
CSL312 (High)
Subjects with C1-INH HAE receiving high dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
Secondary
Area Under the Concentration-time Curve in 1 Dosing Interval (AUC0-tau) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
PK
Posted
Mean
Standard Deviation
h*μg/mL
13 weeks
ID
Title
Description
OG000
Placebo
Subjects with C1-INH HAE receiving buffer only
Placebo: Buffer without active ingredient
OG001
CSL312 (Low)
Subjects with C1-INH HAE receiving low dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG002
CSL312 (Med)
Subjects with C1-INH HAE receiving medium dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG003
CSL312 (High)
Subjects with C1-INH HAE receiving high dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
Secondary
Time of Maximum Concentration (Tmax) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
PK
Posted
Median
Full Range
hours
13 weeks
ID
Title
Description
OG000
Placebo
Subjects with C1-INH HAE receiving buffer only
Placebo: Buffer without active ingredient
OG001
CSL312 (Low)
Subjects with C1-INH HAE receiving low dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG002
CSL312 (Med)
Subjects with C1-INH HAE receiving medium dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG003
CSL312 (High)
Subjects with C1-INH HAE receiving high dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG004
Secondary
Terminal Elimination Half-life (T1/2) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
PK
Posted
Mean
Standard Deviation
hours
13 weeks
ID
Title
Description
OG000
Placebo
Subjects with C1-INH HAE receiving buffer only
Placebo: Buffer without active ingredient
OG001
CSL312 (Low)
Subjects with C1-INH HAE receiving low dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG002
CSL312 (Med)
Subjects with C1-INH HAE receiving medium dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG003
CSL312 (High)
Subjects with C1-INH HAE receiving high dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG004
Secondary
Clearance (CL/F) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
PK
Posted
Mean
Standard Deviation
L/hour
13 weeks
ID
Title
Description
OG000
Placebo
Subjects with C1-INH HAE receiving buffer only
Placebo: Buffer without active ingredient
OG001
CSL312 (Low)
Subjects with C1-INH HAE receiving low dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG002
CSL312 (Med)
Subjects with C1-INH HAE receiving medium dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG003
CSL312 (High)
Subjects with C1-INH HAE receiving high dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG004
Secondary
Volume of Distribution During the Elimination Phase (Vz/F) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
PK
Posted
Mean
Standard Deviation
Liters
13 weeks
ID
Title
Description
OG000
Placebo
Subjects with C1-INH HAE receiving buffer only
Placebo: Buffer without active ingredient
OG001
CSL312 (Low)
Subjects with C1-INH HAE receiving low dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG002
CSL312 (Med)
Subjects with C1-INH HAE receiving medium dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG003
CSL312 (High)
Subjects with C1-INH HAE receiving high dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
Secondary
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
Adverse events of special interest is defined as anaphylaxis, thromboembolic events, and bleeding events.
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.
Posted
Number
Number of participants
13 weeks
ID
Title
Description
OG000
Placebo
Subjects with C1-INH HAE receiving buffer only
Placebo: Buffer without active ingredient
OG001
CSL312 (Low)
Subjects with C1-INH HAE receiving low dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
OG002
CSL312 (Med)
Subjects with C1-INH HAE receiving medium dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
Time Frame
Approximately 129 weeks per participant
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.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Placebo
Subjects with C1-INH HAE receiving buffer only
Placebo: Buffer without active ingredient
0
8
0
8
7
8
EG001
CSL312 (Low)
Subjects with C1-INH HAE receiving low dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
0
9
0
9
7
9
EG002
CSL312 (Med)
Subjects with C1-INH HAE receiving medium dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
0
8
0
8
7
8
EG003
CSL312 (High)
Subjects with C1-INH HAE receiving high dose CSL312
Factor XIIa antagonist monoclonal antibody: Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use
0
7
0
7
7
7
EG004
CSL312 (Med/High)
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
0
6
0
6
4
6
EG005
CSL312 (Med-Period 2)
Subjects with C1-INH HAE receiving medium dose CSL312
0
36
1
36
25
36
EG006
CSL312 (Med/High-Period 2)
Subjects with C1-INH HAE receiving medium/high dose CSL312
0
3
0
3
2
3
EG007
CSL312 (High-Period 2)
Subjects with C1-INH HAE receiving high dose CSL312
0
18
1
18
17
18
EG008
CSL312 (FXII/PLG HAE-Period 1)
Subjects with FXII/PLG HAE (Hereditary Angioedema with Normal C1-esterase Inhibitor and Factor XII or Plasminogen Gene Mutation) receiving high dose CSL312
0
6
1
6
1
6
EG009
CSL312 (FXII/PLG HAE-Period 2)
Subjects with FXII/PLG HAE (Hereditary Angioedema with Normal C1-esterase Inhibitor and Factor XII or Plasminogen Gene Mutation) receiving high dose CSL312