Long-term Safety and Efficacy of CSL312 (Garadacimab) in the Prophylactic Treatment of Hereditary Angioedema Attacks

Study Overview
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Brief Summary
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This phase 3b study will evaluate long-term safety and efficacy of CSL312 (also known as garadacimab) when administered subcutaneously (SC)

Official Title
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An Open-label Study to Evaluate the Long-term Safety and Efficacy of CSL312 (Garadacimab) in the Prophylactic Treatment of Hereditary Angioedema

Conditions
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Hereditary Angioedema

Intervention / Treatment
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* Biological: CSL312


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females aged ≥ 12 years Diagnosed with clinically confirmed C1-INH HAE Experienced ≥ 3 HAE attacks during the 3 months before Screening Participated in the Run-in Period for at least 1 month (CSL312-naïve subjects only) Experienced at least an average of 1 HAE attack per month during the Run-in Period Exclusion Criteria: Concomitant diagnosis of another form of angioedema, such as idiopathic or acquired angioedema or recurrent angioedema associated with urticaria Use of C1-INH products, androgens, antifibrinolytics or other small molecule medications for routine prophylaxis against HAE attacks at least 2 weeks before the first day of the Run-in Period Use of monoclonal antibodies such as lanadelumab (Takhzyro®) 3 months before the first day of the Run-in Period. Female subjects use estrogen-containing oral contraceptives or hormone replacement therapy within 4 weeks prior to screening Female or male subjects who are fertile and sexually active not using or not willing to use an acceptable method of contraception to avoid pregnancy during the study and for 30 days after receipt of the last dose of CSL312 Pregnant, breastfeeding, or not willing to cease breastfeeding

Ages Eligible for Study
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Minimum Age: 12 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CSL312<br>Fully human immunoglobulin G subclass 4/lambda recombinant inhibitor monoclonal antibody administered subcutaneously | Biological: CSL312<br>* Fully human immunoglobulin G subclass 4/lambda recombinant inhibitor monoclonal antibody<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) |  | Up to 45 months | 
| Percentage of subjects with TEAEs |  | Up to 45 months | 
| TEAEs rates per injection |  | Up to 45 months | 
| TEAEs rates per subject year |  | Up to 45 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The time-normalized number (per month and year) of Hereditary Angioedema (HAE attacks) for the entire study |  | Up to 43 months | 
| The percentage reduction and 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 on Treatment compared to Run-in Period |  | Up to 43 months | 
| The time-normalized number (per month and year) of HAE attacks requiring on-demand treatment in subjects on treatment |  | Up to 43 months | 
| The time-normalized number (per month and year) of moderate and/or severe HAE attacks in subjects on treatment |  | Up to 43 months | 
| Number and percentage of subjects rating their response to therapy as good or excellent |  | Up to 43 months | 
| The number and percentage of subjects experiencing TEAEs |  | Up to 45 months | 
| The number and percentage of subjects experiencing adverse events of special interest (AESIs) |  | Up to 45 months | 
| The number and percentage of subjects experiencing serious adverse events (SAEs), including deaths |  | Up to 45 months | 
| The number and percentage of subjects experiencing CSL312 induced anti-CSL312 antibodies |  | Up to 45 months |