Efficacy and Safety Evaluation of Belzupacap Sarotalocan in Primary Indeterminate Lesions or Small Choroidal Melanoma: A Phase 3 Randomized Controlled Trial

The primary objective of this Phase 3 randomized, masked, controlled trial is to determine the **efficacy** and **safety** of belzupacap sarotalocan (AU-011) compared to sham control in the treatment of primary indeterminate lesions and small choroidal melanoma. This is clinically relevant as it aims to provide a therapeutic option for these ocular conditions, potentially improving patient outcomes by offering a targeted treatment approach.

Secondary objectives include assessing the systemic **pharmacokinetics** (PK) and **immunogenicity** of bel-sar when administered via the suprachoroidal route. These evaluations are crucial for understanding the drug's behavior in the body and its potential to elicit an immune response, which are important factors in the overall assessment of the treatment's safety and effectiveness.

The clinical trial involves a total of **125 participants** diagnosed with **primary indeterminate lesions or small choroidal melanoma**. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on specific criteria, including a clinical diagnosis of primary indeterminate lesion or small choroidal melanoma with documented early growth, and no evidence of metastatic disease confirmed by imaging. Additionally, participants must be treatment-naïve for their condition, although those who received photodynamic therapy more than 12 months prior to enrollment may be considered. The trial includes a vulnerable population, indicating that special considerations are in place to ensure their safety and ethical treatment. Lifestyle factors such as diet, physical activity, and habits are not specified in the available data.

The clinical trial is a **Phase 3 randomized, masked, controlled** study designed to evaluate the efficacy and safety of **belzupacap sarotalocan** compared to a sham control in subjects with primary indeterminate lesions or small choroidal melanoma. The trial aims to determine the time to tumor progression and assess the composite endpoint of tumor progression or visual acuity failure at the Week 65 analysis. The study is expected to commence recruitment on April 1, 2024, and conclude by January 1, 2027.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a clinical diagnosis of primary indeterminate lesions or small choroidal melanoma with documented early growth, absence of metastatic disease, and being treatment-naïve for their condition. Following the screening, eligible participants will be randomized to receive either the investigational product, belzupacap sarotalocan, or a placebo via a sham injection. The investigational product will be administered using the Clearside SCS Microinjector to deliver the solution into the suprachoroidal space.

Throughout the trial, participants will attend regular follow-up visits to monitor safety and efficacy outcomes. These visits will include assessments of tumor progression and visual acuity. The trial will conclude with an end-of-study visit, where final evaluations will be conducted. The expected duration of participant involvement is up to 65 weeks, with the possibility of early termination if significant adverse events occur or if the participant withdraws consent. The trial is not categorized as low intervention, and it is essential to adhere to the protocol to ensure the integrity and validity of the study results.

The clinical trial involves the administration of **Belzupacap Sarotalocan**, an experimental medication formulated as a **solution for injection**. This investigational drug is developed by Aura Biosciences, Inc. and is designated as an orphan drug under the identifier EU/3/22/2599. The active substance, Belzupacap Sarotalocan, is classified as a structurally diverse substance. The medication is administered via the **suprachoroidal** route using the proprietary Clearside SCS Microinjector, which is equipped with a 900 μm needle and a safety cap. The dosing regimen allows for a maximum daily dose of 80 μg and a total dose of 240 μg over a treatment period of up to 3 weeks.

The trial also includes a **placebo** group, which receives a sham injection designed to mimic the administration of Belzupacap Sarotalocan. The placebo is a solution for sham injection with a concentration of 0.0 mg/mL, serving as a control to evaluate the efficacy and safety of the experimental treatment. The placebo does not contain any active substance and is used to maintain the study's masked and controlled design.

The efficacy of **Belzupacap Sarotalocan** in the treatment of primary indeterminate lesions or small choroidal melanoma will be assessed in a Phase 3 randomized, masked, controlled trial. The primary endpoint for evaluating efficacy is the time to reach tumor progression, which will be analyzed at the Week 65 timepoint. Secondary endpoints include the time to reach a composite endpoint, which encompasses tumor progression or visual acuity failure, also assessed at Week 65.

Data collection will involve the use of the Clearside SCS Microinjector for the administration of Belzupacap Sarotalocan into the suprachoroidal space. The trial will compare the efficacy of the active treatment against a sham control. The trial is designed to ensure rigorous assessment of the treatment's impact on disease progression and visual outcomes in the specified patient population. The study is expected to conclude by January 2027, with recruitment starting in April 2024.