Evaluation of Long-Term Safety and Efficacy of GSK1070806 in Moderate to Severe Atopic Dermatitis: A Humanised IgG1 Kappa Monoclonal Antibody Against Interleukin 18 Study

The primary objective of this study is to describe the long-term **safety** of various doses and dosing regimens of GSK1070806 in participants with moderate to severe **atopic dermatitis**. This is clinically relevant as it aims to ensure that the treatment is safe for prolonged use in managing a chronic condition, which is crucial for patient compliance and overall treatment success.

Secondary objectives include evaluating the long-term **efficacy** of a range of doses and dosing regimens of GSK1070806 in the same patient population. This will provide insights into the effectiveness of the treatment over an extended period, which is essential for determining its potential as a sustainable therapeutic option for atopic dermatitis.

The clinical trial involves a total of **92 participants** diagnosed with moderate to severe **atopic dermatitis**. The study population includes both male and female subjects, aged 18 years and older, who have previously completed qualifying Phase 2 parent studies related to atopic dermatitis. Participants were selected based on their potential to benefit from the investigational treatment, GSK1070806, as assessed by the investigator. The trial includes individuals from a vulnerable population, ensuring comprehensive safety data across diverse demographics. Participants are required to adhere to local contraceptive regulations, reflecting the study's commitment to ethical standards. The trial does not specify particular lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the long-term safety and efficacy of **GSK1070806**, a **humanised IgG1 kappa monoclonal antibody against interleukin 18**, in participants with moderate to severe atopic dermatitis. This is a phase 4, randomized, double-blind, controlled trial. The trial will involve the administration of GSK1070806 via subcutaneous injection, with a comparator of locally sourced 0.9% sodium chloride. The trial is expected to commence recruitment on August 22, 2024, and conclude by November 7, 2029, with a maximum treatment period of 60 months.

Participants eligible for inclusion are those who have completed the qualifying phase 2 parent GSK atopic dermatitis studies and are 18 years or older. The primary endpoint is the incidence of adverse events, serious adverse events, and adverse events of special interest. Secondary endpoints include achieving and maintaining a response at specified intervals, measured by the Investigator's Global Assessment (IGA) score and Eczema Area and Severity Index (EASI) reduction.

The sequence of study visits begins with a screening visit to confirm eligibility, followed by regular follow-up visits at weeks 16, 32, 48, and every 48 weeks thereafter. These visits are designed to monitor safety and efficacy outcomes. The end-of-study visit will occur at the conclusion of the participant's involvement in the trial. The expected length of participant involvement is up to 60 months, contingent upon the participant's response to treatment and absence of adverse events. Conditions that may lead to early termination from the study include the occurrence of serious adverse events or if the participant no longer meets the inclusion criteria.

The clinical trial involves the administration of an **experimental medication** known as GSK1070806, a **humanised IgG1 kappa monoclonal antibody against interleukin 18**. This medication is provided as a 100 mg/ml solution for **injection**. The pharmaceutical form is specifically designed for **subcutaneous use**. The trial aims to evaluate the long-term safety and efficacy of GSK1070806 in participants with moderate to severe **atopic dermatitis**. The dosing regimen and frequency of administration are determined based on the study protocol, with a maximum treatment period of 60 days. The medication is manufactured by GlaxoSmithKline and is not a paediatric formulation. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol.

In addition to the experimental medication, the study utilizes a **non-experimental treatment** in the form of a placebo, which is locally sourced 0.9% sodium chloride. This placebo is used to maintain the study's integrity by providing a comparator treatment against which the effects of GSK1070806 can be measured. The sodium chloride solution is administered in a manner consistent with the experimental medication to ensure blinding and consistency in the trial's methodology. The placebo does not have a specific pharmaceutical form or active substance designation, as it serves solely as a control within the study framework.

The efficacy of GSK1070806 in participants with moderate to severe **Atopic Dermatitis** will be assessed through several secondary endpoints. These include achieving a response at specified timepoints, such as Weeks 16, 32, 48, and every 48 weeks thereafter. The response criteria are defined as an Investigator's Global Assessment (IGA) score of 0 or 1, a reduction of at least 75% from baseline in the Eczema Area and Severity Index (EASI), and a reduction of 4 points or more in the Peak Pruritus Numerical Rating Scale (PP-NRS). Additionally, the maintenance of these responses will be evaluated for at least 16, 32, 48 weeks, and every 48 weeks thereafter following the initial response. The continuous endpoint of percentage change from baseline (PCFB) in the EASI will also be measured at the same intervals.