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

Study Overview
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Brief Summary
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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.

Official Title
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A Multicenter, Randomized, Placebo-controlled, Parallel-arm Study to Investigate the Efficacy, Pharmacokinetics, and Safety of CSL312 in Subjects With Hereditary Angioedema

Conditions
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Hereditary Angioedema

Intervention / Treatment
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* Biological: Factor XIIa antagonist monoclonal antibody
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 Known incurable malignancies

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects are assigned to 1 of 2 or more groups in parallel for the duration of the study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Subjects with C1-INH HAE receiving buffer only | Drug: Placebo<br>* Buffer without active ingredient<br>|
| Active Comparator: CSL312 (low)<br>Subjects with C1-INH HAE receiving low dose CSL312 | Biological: Factor XIIa antagonist monoclonal antibody<br>* Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use<br>* Other names: CSL312;|
| Active Comparator: CSL312 (med)<br>Subjects with C1-INH HAE receiving medium dose CSL312 | Biological: Factor XIIa antagonist monoclonal antibody<br>* Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use<br>* Other names: CSL312;|
| Active Comparator: CSL312 (high)<br>Subjects with C1-INH HAE receiving high dose CSL312 | Biological: Factor XIIa antagonist monoclonal antibody<br>* Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use<br>* Other names: CSL312;|
| Active Comparator: CSL312 (med/high)<br>Subjects with C1-INH HAE receiving medium/high dose CSL312 | Biological: Factor XIIa antagonist monoclonal antibody<br>* Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use<br>* Other names: CSL312;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 Outcome Measures

| Outcome Measure | 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 | 
| 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 |