Efficacy and Safety Evaluation of Depemokimab in Adults with Hypereosinophilic Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of this study is to evaluate the **efficacy** of depemokimab administered subcutaneously compared to placebo in participants with uncontrolled **Hypereosinophilic Syndrome (HES)** who are receiving standard of care. This is clinically relevant as it aims to determine the potential of depemokimab to improve clinical outcomes in a population with limited treatment options, thereby addressing an unmet medical need.

Secondary objectives include assessing supportive evidence of the efficacy of depemokimab SC versus placebo on multiple clinical outcomes in participants with uncontrolled HES receiving standard of care. This will provide additional insights into the therapeutic benefits and potential broader impacts of depemokimab on patient health and quality of life.

The clinical trial involves a total of **82 participants** diagnosed with **Hypereosinophilic Syndrome (HES)**. The study population includes both male and female adults aged 18 years and older, with a minimum weight of 40 kg. Participants were selected based on a documented diagnosis of HES, characterized by blood eosinophilia of more than 1,500 eosinophils/μL on at least two occasions at a minimum one-month interval, without a discernible non-hematological secondary cause, and signs or symptoms of organ involvement or dysfunction directly related to eosinophilia. The trial includes individuals with a history of two or more HES flares within the past 12 months. Both genders are represented, and the study considers vulnerable populations. Participants are required to comply with contraceptive measures if applicable, and all have provided informed consent. The trial aims to evaluate the efficacy of depemokimab subcutaneous versus placebo in participants with uncontrolled HES receiving standard care.

The clinical trial is designed as a **randomized, double-blind, placebo-controlled** study to evaluate the efficacy and safety of **depemokimab** in adults diagnosed with **Hypereosinophilic Syndrome (HES)**. The trial will span a total duration of 52 weeks, during which participants will receive either depemokimab or a placebo. The primary objective is to assess the frequency of HES flares during the study period, with secondary endpoints including the time to the first HES flare and changes in fatigue levels as measured by the Brief Fatigue Inventory.

Participants will be involved in the study for the entire 52-week period unless early termination is warranted. Conditions that may lead to early termination include non-compliance with the study protocol, adverse events, or withdrawal of consent. The study will commence with an inclusion (screening) visit to confirm eligibility based on criteria such as age, weight, and documented diagnosis of HES. Following the screening, participants will be randomized to receive either the active treatment or placebo.

Study visits will be scheduled at regular intervals to monitor the participants' health status, adherence to the treatment regimen, and any potential side effects. These visits will also include assessments of HES flare frequency and severity, as well as evaluations of overall health and quality of life. The end-of-study visit will occur at the conclusion of the 52-week period, where final assessments will be conducted to gather comprehensive data on the efficacy and safety of the treatment.

The trial will involve the administration of depemokimab via **subcutaneous injection** and the use of **prednisolone** tablets as part of the standard of care. The study is not categorized as low intervention and is classified as a Phase III trial, indicating its advanced stage in the clinical research process. Participants are expected to comply with all study requirements, including the use of effective contraception for women of childbearing potential, to ensure the integrity and reliability of the trial outcomes.

The clinical trial involves the administration of **Depemokimab**, an experimental medication developed by GlaxoSmithKline. Depemokimab is a **solution for injection** and is administered via **subcutaneous use**. The active substance is a humanized immunoglobulin G1-kappa monoclonal antibody targeting interleukin 5. The medication is provided in a pre-filled syringe, designed for single-use, ensuring precise delivery of the drug product. The dosing schedule and frequency of administration are determined by the study protocol, with a maximum treatment period of 52 weeks. Participant compliance is monitored throughout the trial to ensure adherence to the dosing regimen.

In addition to the experimental treatment, the study includes the administration of **Prednisolone**, a standard-of-care therapy. Prednisolone is provided in **tablet** form and is administered **orally**. The maximum daily dose is 40 mg, with a total maximum dose of 7520 mg over the course of the study. Prednisolone tablets are overcapsulated for study purposes to maintain blinding. The treatment period for Prednisolone is also up to 52 weeks, and participant compliance is closely monitored to ensure accurate dosing.

The trial also incorporates the use of placebos to maintain the double-blind design. A **placebo for Prednisolone** is included, which mimics the appearance of the active Prednisolone tablets but contains no active substance. Similarly, a **placebo for Depemokimab Injection** is used, which is designed to resemble the Depemokimab solution for injection but lacks the active ingredient. These placebos are critical for maintaining the integrity of the study by ensuring that neither the participants nor the investigators know which treatment is being administered, thus reducing bias in the assessment of the treatment's efficacy and safety.

The efficacy of **Depemokimab** in the treatment of Hypereosinophilic Syndrome (HES) will be assessed through a randomized, double-blind, placebo-controlled clinical trial. The primary endpoint for evaluating efficacy is the frequency of HES flares during the 52-week study intervention period. Secondary endpoints include the time to the first HES flare, the occurrence of at least one HES flare during the study period, and the change from baseline to week 52 in the weekly average score of Brief Fatigue Inventory (BFI) item 3.

Measurements will be collected at specified intervals throughout the trial, with the primary and secondary endpoints being analyzed to determine the efficacy of the treatment. The trial will involve the administration of Depemokimab via subcutaneous injection, with the use of a pre-filled syringe designed for single-use, disposable delivery. The study will compare the effects of Depemokimab against a placebo, with all participants receiving standard of care treatment for HES. The data collected will be analyzed to assess the impact of Depemokimab on the frequency and severity of HES flares, as well as its effect on patient-reported outcomes related to fatigue.