Evaluation of Long-Term Safety and Efficacy of STAR-0215 in Adult Patients with Type 1 or Type 2 Hereditary Angioedema

The primary objective of this study is to assess the long-term **safety** and tolerability of STAR-0215 in participants with Type 1 or Type 2 **hereditary angioedema** (HAE). This is clinically relevant as it aims to ensure that the repeated dosing of STAR-0215 is safe for long-term use in managing HAE, a condition characterized by recurrent episodes of severe swelling.

Secondary objectives include:

• Assessing the long-term efficacy of STAR-0215 in participants with Type 1 or Type 2 HAE, which is crucial for determining the therapeutic benefits of the treatment over an extended period.
• Characterizing the pharmacokinetics (PK) of long-term STAR-0215 dosing, providing insights into the drug's absorption, distribution, metabolism, and excretion in the body.
• Characterizing the pharmacodynamics (PD) of long-term STAR-0215 dosing, which will help understand the drug's biological effects and mechanism of action.
• Assessing the immunogenicity of STAR-0215 when dosed long-term, which is important for evaluating the potential for immune responses that could affect the drug's safety and efficacy.

The clinical trial involves a total of **35 participants** diagnosed with **Hereditary Angioedema** (HAE), specifically Type 1 or Type 2. The study population includes both male and female subjects, aged 18 years and older, who are in general good health aside from their HAE condition. Participants were selected based on their previous involvement in the STAR-0215-201 trial or their documented diagnosis of HAE, with specific criteria regarding their clinical history and laboratory test results. The trial does not include a vulnerable population. Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria. The study aims to assess the long-term safety and tolerability of STAR-0215 in this population.

The clinical trial is designed to evaluate the long-term safety and tolerability of **STAR-0215**, a **sterile solution** administered via **subcutaneous use**, in adult patients diagnosed with **hereditary angioedema** (HAE). This is a Phase 2, open-label trial, which means that both the researchers and participants are aware of the treatment being administered. The trial is expected to commence recruitment in December 2024 and is estimated to conclude by March 2031. Participants will be involved in the study for a maximum treatment period of 60 months, during which they will receive repeat dosing of STAR-0215.

The trial will include several study visits, beginning with a screening visit to confirm eligibility based on specific inclusion criteria, such as age and documented diagnosis of HAE. Participants who have previously been involved in the STAR-0215-201 study or are STAR-0215-naïve will be considered for inclusion. The primary endpoint of the trial is the incidence of adverse events, while secondary endpoints include changes in the monthly HAE attack rate, severity, duration, and the number of attacks requiring on-demand therapy. The trial will also assess the concentration of STAR-0215, changes in plasma kallikrein activity, and the formation of anti-drug antibodies.

Follow-up visits will be scheduled to monitor the participants' response to the treatment and to collect data on the primary and secondary endpoints. The end-of-study visit will mark the conclusion of the participant's involvement in the trial, where final assessments will be conducted. Participants may be withdrawn from the study early if they experience significant adverse events or if they choose to discontinue participation for personal reasons. The trial aims to provide valuable insights into the long-term management of hereditary angioedema with STAR-0215, contributing to the understanding of its safety and efficacy profile.

The clinical trial involves the administration of **STAR-0215**, an investigational medication developed by Astria Therapeutics, Inc. **STAR-0215** is formulated as a **sterile solution** and is intended for **subcutaneous use**. The active substance in **STAR-0215** is a protein of other origin, specifically designed for the treatment of hereditary angioedema (HAE). The trial aims to assess the long-term safety and tolerability of **STAR-0215** in adult patients with Type 1 or Type 2 HAE. The dosing regimen involves repeat administration over a maximum treatment period of 60 days. The specific dosage and frequency of administration are determined by the study protocol, ensuring adherence to safety guidelines.

In this trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus remains solely on evaluating the effects of **STAR-0215**. Participant compliance with the dosing schedule is monitored throughout the study to ensure accurate assessment of the medication's safety and efficacy. The trial does not include any pediatric formulations, and **STAR-0215** is not classified as an orphan drug. The study is conducted under the authorization code DE_BW_01_MIA_2022_0034/DE_BW_01_Catalent Germany Schorndorf, adhering to regulatory standards for clinical research.

Efficacy in the clinical trial will be assessed using several secondary endpoints related to **hereditary angioedema (HAE)**. These include the change from baseline in the monthly HAE attack rate, the incidence of monthly HAE attack severity categorized as mild, moderate, and severe, and the duration of monthly HAE attacks, which will be classified as shorter than 12 hours, 12 to 24 hours, 24 to 48 hours, and longer than 48 hours. Additionally, the number of monthly HAE attacks requiring on-demand therapy, the time to the first HAE attack after each dose, and the number of HAE attack-free days will be evaluated. The proportion of HAE attack-free participants, defined as those having zero HAE attacks during the specified treatment period, will also be measured.

Further efficacy assessments will include the concentration of STAR-0215 and the derived pharmacokinetic (PK) parameters, the change in plasma kallikrein activity, and the formation of anti-drug (STAR-0215) antibodies. These parameters will be collected and analyzed at predetermined intervals throughout the trial to provide a comprehensive evaluation of the treatment's efficacy in managing HAE symptoms. The data collection and analysis will be conducted using validated methods to ensure accuracy and reliability in the assessment of STAR-0215's therapeutic effects.