Long-term Safety Evaluation of Depemokimab in Adults and Adolescents with Severe Eosinophilic Asthma: An Open-Label Extension Study

The primary objective of this study is to describe the long-term **safety** profile of GSK3511294 (Depemokimab) administered at a dose of 100 mg subcutaneously every 26 weeks in participants with severe asthma with an eosinophilic phenotype. This evaluation is conducted over a 12-month open-label extension phase, in conjunction with existing asthma therapy. Understanding the safety profile is clinically relevant as it informs healthcare providers about the potential risks associated with long-term use of this treatment in managing severe asthma, particularly in patients with an eosinophilic phenotype.

Secondary objectives include evaluating the effects of long-term dosing of GSK3511294 on a range of clinical markers of asthma control and additional efficacy assessments. These evaluations are conducted over the same 12-month open-label extension phase, providing insights into the therapeutic benefits and potential improvements in asthma management when added to existing therapy.

The clinical trial involves a total of **378 participants** diagnosed with **severe asthma with an eosinophilic phenotype**. The study population includes both male and female subjects, with an age range starting from 12 years and above, although in Germany and the UK, only adults aged 18 years and older are included. Participants were selected based on their completion of a prior double-blind study intervention treatment during Study 206713 or Study 213744. The trial includes individuals who are capable of providing informed consent and are compliant with the study's requirements. Participants are required to continue their existing asthma therapy throughout the study. The trial population is diverse, including both adolescents and adults, and considers vulnerable populations. Lifestyle factors such as diet and physical activity are not specified in the available data. The study ensures that female participants of childbearing potential adhere to strict contraceptive measures to prevent pregnancy during the trial period.

The clinical trial is designed to evaluate the long-term safety profile of **depemokimab** in participants with severe asthma with an eosinophilic phenotype. This study is an open-label extension, allowing participants who have completed previous double-blind studies (206713 or 213744) to continue receiving the investigational product. The trial is structured as a single-arm study, where all participants receive **depemokimab** administered subcutaneously at a dose of 100 mg every 26 weeks, in addition to their existing asthma therapy. The trial is expected to last for 12 months, with the primary focus on assessing the incidence of adverse events and immunogenicity over a 52-week period.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, completion of prior studies, and informed consent. Following the screening, participants will receive the first dose of the investigational product. Subsequent follow-up visits will be scheduled at regular intervals to monitor safety, collect data on adverse events, and assess secondary endpoints such as changes in asthma control and lung function. The end-of-study visit will occur at the conclusion of the 52-week treatment period, where final assessments will be conducted.

The expected duration of participant involvement is approximately 12 months, aligning with the trial's overall duration. Conditions that may lead to early termination from the study include the occurrence of serious adverse events, withdrawal of consent, or non-compliance with study procedures. The trial aims to provide comprehensive safety data on **depemokimab** in a real-world setting, contributing valuable insights into its long-term use in managing severe asthma with an eosinophilic phenotype.

The clinical trial involves the administration of **Depemokimab**, an experimental medication developed by GlaxoSmithKline. Depemokimab is a **solution for injection** and is classified as a **humanized immunoglobulin G1-kappa monoclonal antibody** targeting interleukin 5. The pharmaceutical form of Depemokimab is a solution intended for **subcutaneous use**. The dosing regimen for this trial specifies a maximum daily dose of 100 mg, with a total maximum dose of 200 mg over the course of the study. The treatment period extends up to 52 weeks, with the medication administered every 26 weeks. The drug is delivered using a drug-device combination product, which includes a prefilled syringe assembled in a safety syringe device.

Participants in the trial will continue their existing asthma therapy as part of the study's design. This non-experimental treatment serves as the standard-of-care therapy for individuals with severe asthma with an eosinophilic phenotype. The trial aims to evaluate the long-term safety profile of Depemokimab when used in conjunction with these standard treatments. Compliance with the dosing schedule and administration will be monitored throughout the study to ensure adherence to the protocol.

Efficacy in this clinical trial will be assessed using both primary and secondary endpoints. The primary endpoints include the incidence of adverse events (AEs) and serious adverse events (SAEs) over a 52-week period, as well as the incidence of immunogenicity, measured by the presence of anti-drug antibody (ADA) and neutralizing antibody (Nab) to **GSK3511294** over the same duration. These parameters will provide insights into the safety and immunogenic response associated with the treatment.

Secondary endpoints will focus on the clinical efficacy of the treatment. These include the annualized rate of clinically significant exacerbations over 52 weeks, changes from baseline in the Asthma Control Questionnaire-5 (ACQ-5) score at discrete timepoints during the 52-week period, changes from baseline in the St. George's Respiratory Questionnaire (SGRQ) total score at Week 26 and Week 52, and changes from baseline in prebronchodilator FEV1 at Week 26 and Week 52. These measures will be collected and analyzed to evaluate the impact of the treatment on asthma control and respiratory function.