Evaluation of Safety in Hereditary Angioedema Patients Aged ≥12 Years Transitioning to Garadacimab from Current Prophylactic Treatment

The primary objective of this phase 4 open-label study is to evaluate the **safety** of switching to **garadacimab** from a marketed KK inhibitor or pdC1INH prophylactic treatment in subjects aged 12 years and older with **Hereditary Angioedema (HAE)**. This evaluation is clinically relevant as it aims to ensure that transitioning to garadacimab, a solution for injection, does not compromise patient safety, which is crucial for maintaining effective management of HAE symptoms.

The clinical trial involves a total of **27 participants** diagnosed with **Hereditary Angioedema (HAE)**. The study population includes both male and female subjects aged **12 years and older**. Participants were selected based on their history of response to on-demand HAE treatment for acute attacks and a documented laboratory diagnosis of HAE-C1INH type 1 or type 2, or HAE-nC1INH, as evidenced by specific genetic mutations or laboratory findings. All subjects have been using lanadelumab, berotralstat, or pdC1INH for prophylactic treatment and have maintained a stable medication regimen for at least three months prior to screening. The trial includes a vulnerable population, ensuring careful consideration of ethical standards in the selection and management of participants. The study aims to evaluate the safety of switching to garadacimab from a marketed KK inhibitor or pdC1INH prophylactic treatment in this specific cohort.

The clinical trial is designed to evaluate the safety of **garadacimab** in subjects aged 12 years and older with **Hereditary Angioedema (HAE)** who are switching from their current prophylactic treatment. This is a phase IV, open-label study, which means that both the researchers and participants know which treatment is being administered. The trial aims to assess the safety profile of garadacimab when used as a substitute for existing prophylactic treatments such as lanadelumab, berotralstat, or pdC1INH. The primary endpoints include the number and percentage of participants experiencing treatment-emergent adverse events (TEAEs), as well as the rate of TEAEs per injection and per participant year. Secondary endpoints focus on serious adverse events (SAEs), deaths, and the presence of anti-garadacimab antibodies, among others.

The trial is expected to commence recruitment on August 1, 2025, and conclude by June 15, 2026. Participants will be involved in the study for a maximum treatment period of three months. The study visits are structured to include an initial screening visit to confirm eligibility based on criteria such as age, history of response to on-demand HAE treatment, and documented laboratory diagnosis of HAE-C1INH type 1 or type 2. Follow-up visits will be scheduled to monitor the safety and efficacy of the treatment, with the end-of-study visit marking the conclusion of the participant's involvement. Conditions that may lead to early termination from the study include the occurrence of severe adverse events or the participant's decision to withdraw consent. The study will be conducted under strict adherence to ethical guidelines and regulatory requirements to ensure the safety and well-being of all participants.

The clinical trial involves the administration of **garadacimab**, an experimental medication, to evaluate its safety in subjects with hereditary angioedema (HAE) aged 12 years and older. Garadacimab is provided in the form of a **solution for injection** and is administered via the **subcutaneous route**. The maximum daily dose of garadacimab is 400 mg, with a total maximum dose of 800 mg over the course of the treatment period. The treatment period is limited to a maximum of 3 months. Garadacimab is a protein-based therapeutic agent, specifically classified under the category of "Protein - Other." The product is developed and supplied by CSL Behring LLC, and it is identified by the sponsor product code CSL312.

In this study, participants will transition from their current prophylactic HAE treatment, which may include a marketed KK inhibitor or plasma-derived C1 inhibitor (pdC1INH), to garadacimab. The trial does not involve the use of a placebo or any additional comparator treatments. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the prescribed regimen. The trial is designed to assess the safety profile of garadacimab when used as a replacement for existing prophylactic therapies in the specified patient population.

The efficacy of the clinical trial involving **garadacimab** will be assessed through a series of primary and secondary endpoints. The primary endpoints focus on the safety profile of the treatment, specifically evaluating the number and percentage of participants experiencing Treatment Emergent Adverse Events (TEAEs), as well as the rate of TEAEs per injection and per participant year. These parameters will provide insight into the immediate and long-term safety of switching to garadacimab from current prophylactic treatments for Hereditary Angioedema (HAE).

Secondary endpoints will further explore the safety and immunogenicity of garadacimab. These include the number and percentage of participants with Serious Adverse Events (SAEs), deaths, and TEAEs that are related to treatment, lead to study discontinuation, or vary in severity. Additionally, the presence of anti-garadacimab antibodies will be measured, alongside plasma concentrations of garadacimab. The study will also assess participant preference for garadacimab, providing a comprehensive evaluation of both the safety and acceptability of the treatment.