CSL312_3003 Safety and Pharmacokinetic Study in Subjects 2 to 11 Years of Age With Hereditary Angioedema

Study Overview
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Brief Summary
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The purpose of this study is to investigate the safety, PK / PD, and efficacy of SC CSL312 for prophylactic treatment of pediatric subjects with HAE.

Official Title
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A Phase 3 Open-label Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of CSL312 (Garadacimab) in the Prophylactic Treatment of Hereditary Angioedema in Pediatric Subjects 2 to 11 Years of Age

Conditions
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Hereditary Angioedema (HAE)

Intervention / Treatment
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* Biological: CSL312


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female Aged 2 to 11 years, inclusive, with body weight ≥ 10th percentile based on age Diagnosed with clinically confirmed C1-INH HAE Experienced ≥ 2 HAE attacks during the 6 months before Screening Exclusion Criteria: Concomitant diagnosis of another form of angioedema, such as idiopathic or acquired angioedema, recurrent angioedema associated with urticaria, or HAE type III Any preplanned major surgeries or procedures during the clinical study Use of C1-INH products, androgens, antifibrinolytics, approved or future approved medications, or other small molecule medications for routine prophylaxis against HAE attacks Participation in another interventional clinical study

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 11 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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CSL312<br>Ages 2-5 years and 6-11 years will have specific subcutaneous dosing schedules | Biological: CSL312<br>* Fully human immunoglobulin G subclass 4/lambda recombinant inhibitor monoclonal antibody administered subcutaneously (SC)<br>* Other names: Garadacimab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with treatment emergent adverse events (TEAEs) |  | At least 14 months | 
| Percent of subjects with TEAEs |  | At lease 14 months | 
| Number of TEAEs |  | At least 14 months | 
| TEAE rates per injection |  | At least 14 months | 
| TEAE rates per subject year |  | At least 14 months | 
| Maximum concentration (Cmax) of CSL312 at steady-state |  | At least 12 months | 
| Trough concentration (Ctrough) of CSL312 at steady-state |  | At least 12 months | 
| Time to maximum concentration (Tmax) of CSL312 at steady-state |  | At least 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-normalized number of HAE attacks per month and per year |  | At least 12 months | 
| Time-normalized number of HAE attacks treated with on-demand treatment per month and per year |  | At least 12 months | 
| Time-normalized number of moderate and / or severe HAE attacks per month and per year |  | At least 12 months | 
| Percentage reduction in the time-normalized number of HAE attacks |  | At least 12 months | 
| The number of subjects experiencing at least ≥ 50%, ≥ 70%, ≥ 90%, or equal to 100% (attack-free) reduction in the time-normalized number of HAE attacks |  | At least 12 months | 
| Number of subjects with serious adverse events (SAEs) |  | At least 14 months | 
| Percent of subjects with SAEs |  | At least 14 months | 
| Number of subjects experiencing death |  | At least 14 months | 
| Percent of subjects experiencing death |  | At least 14 months | 
| Number of subjects with related TEAEs |  | At least 14 months | 
| Percent of subjects with related TEAEs |  | At least 14 months | 
| Number of subjects with TEAEs leading to study discontinuation |  | At least 14 months | 
| Percent of subjects with TEAEs leading to study discontinuation |  | At least 14 months | 
| Number of subjects with TEAEs by severity |  | At least 14 months | 
| Percent of subjects with TEAEs by severity |  | At least 14 months | 
| Number of subjects with Anti-CSL312 antibodies |  | At least 14 months | 
| Percent of subjects with Anti-CSL312 antibodies |  | At least 14 months | 
| Number of subjects with adverse events of special interest (AESIs) |  | At least 14 months | 
| Percent of subjects with AESIs |  | At least 14 months | 
| FXIIa-mediated kallikrein activity | Blood samples will be collected on the same day as CSL312 administration for assessment of FXIIa-mediated kallikrein activity | At least 12 months |