Efficacy and Safety Evaluation of GSK1070806 in Adults with Moderate to Severe Atopic Dermatitis: A Randomized, Double-Blind, Placebo-Controlled Phase 2b Study

Trial ID: 2023-505414-15-00
Protocol: 219538
Sponsor: Glaxosmithkline Research & Development Limited

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Diseases & Conditions

Dermatitis atopic

Objectives

The primary objective of this Phase 2b, randomized, double-blind, parallel group, placebo-controlled, dose-finding study is to evaluate the **efficacy** of GSK1070806, a humanized IgG1 kappa monoclonal antibody against interleukin 18, compared to placebo in adult participants with moderate to severe **atopic dermatitis**. This objective is clinically relevant as it aims to determine the potential therapeutic benefit of GSK1070806 in reducing the severity of symptoms associated with this chronic inflammatory skin condition, which can significantly impact patients' quality of life.

Participants

The clinical trial involves a total of **103 participants** diagnosed with **atopic dermatitis** (AtD), specifically targeting adults aged 18 to 75 years. The study population includes both male and female subjects, with no vulnerable populations selected. Participants were chosen based on specific criteria, including a **Body Mass Index (BMI)** within the range of 18 to 39.9 kg/m². The trial focuses on individuals with moderate to severe AtD, as defined by the American Academy of Dermatology Consensus Criteria. Participants must have had a diagnosis of AtD for at least one year, with an Investigator's Global Assessment (IGA) score of 3 or higher, and an Eczema Area and Severity Index (EASI) score of 16 or more at both screening and baseline visits. Additionally, participants are required to have a baseline pruritus numerical rating scale average score for maximum intensity of at least 3. Lifestyle considerations include the application of a stable dose of non-medicated topical moisturizer at least twice daily for seven days prior to the baseline visit. The trial includes both biologic-experienced and biologic-naive participants, with specific conditions for each group regarding previous treatments and responses. Participants are required to complete electronic diary entries for the pruritus numerical rating scale for a minimum of four out of seven days preceding randomization.

Plans and Procedures

The clinical trial is a **Phase 2b**, randomized, double-blind, parallel-group, placebo-controlled study designed to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of GSK1070806 subcutaneous injection in adult participants with moderate to severe **atopic dermatitis**. The trial will involve a comparison between the investigational product, a humanized IgG1 kappa monoclonal antibody against interleukin 18, and a placebo, which is locally sourced 0.9% sodium chloride. The study is expected to last for approximately 16 weeks, with participant involvement beginning from the screening visit and concluding at the end-of-study visit.

Participants will undergo a series of study visits, starting with an inclusion (screening) visit to assess eligibility based on criteria such as age, body mass index, and disease characteristics. Eligible participants will be randomized to receive either the investigational product or placebo. The primary endpoint is the percent change from baseline in the Eczema Area and Severity Index (EASI) at week 16. Follow-up visits will be conducted to monitor the participants' response to treatment, collect safety data, and assess pharmacokinetic and pharmacodynamic parameters. The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be conducted.

Participants are expected to be involved in the study for the entire 16-week duration unless conditions arise that necessitate early termination. Such conditions may include adverse events, non-compliance with study procedures, or withdrawal of consent. The trial aims to provide valuable insights into the potential benefits and risks associated with the investigational product in treating moderate to severe atopic dermatitis.

Treatment

The clinical trial involves the administration of an **experimental medication** known as GSK1070806, which is a **humanised IgG1 kappa monoclonal antibody against interleukin 18**. This medication is provided in the form of a 100 mg/ml solution for injection. The pharmaceutical form is an injection, and the route of administration is subcutaneous. The dosing schedule is designed to be flexible, with a maximum treatment period of 16 weeks. The medication is developed by GlaxoSmithKline and is not a paediatric formulation. The trial aims to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of this experimental treatment in adult participants with moderate to severe atopic dermatitis.

In addition to the experimental treatment, the study utilizes a **placebo** control, which is locally sourced 0.9% sodium chloride. This placebo is used to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators know who is receiving the experimental treatment versus the placebo. The placebo is administered in a manner consistent with the experimental treatment to ensure comparability between the groups. The use of a placebo is critical in assessing the true efficacy and safety profile of GSK1070806 by providing a baseline for comparison.

Efficacy

The efficacy of the investigational product, GSK1070806, will be assessed in a Phase 2b clinical trial involving adult participants with moderate to severe **Atopic Dermatitis**. The primary endpoint for evaluating efficacy is the percent change from baseline in the Eczema Area and Severity Index (EASI) at Week 16. This endpoint will provide a quantitative measure of the improvement in the severity and extent of eczema over the course of the treatment period.

Participants will receive GSK1070806 via subcutaneous injection, and the efficacy assessments will be conducted at specified intervals throughout the trial. The EASI scores will be collected and analyzed to determine the treatment's impact on the disease. The trial is designed as a randomized, double-blind, placebo-controlled, dose-finding study, ensuring that the efficacy results are robust and reliable. The study will follow a parallel group design to compare the effects of the investigational product against a placebo, providing a clear understanding of its therapeutic potential in the target population.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Participant and/or their LAR must sign and date an informed consent.
Adult participants 18 years to 75 years of age • Country specific requirement: Participants from South Korea are required to be aged at least 19 years or greater in the study. Participants from Thailand are required to be aged at least 20 years or greater in the study.
BMI within the range 18 - 39.9 kg/m2 (inclusive).
Disease Characteristics • AtD defined by the AAD Consensus Criteria [Eichenfield, 2014] (see Appendix 8). • Diagnosis of AtD ≥1 year • An IGA score ≥3 at both the Screening and Baseline visits • AtD involvement of ≥10% BSA at both the Screening and Baseline visits • EASI score ≥16 at both the Screening and Baseline visits • Baseline pruritus numerical rating scale average score for maximum intensity of at least 3, based on the average of daily pruritus numerical rating scale scores for maximum itch intensity reported during the 7 days prior to randomization.
AtD Medications: Biologic experienced participants: may have had exposure to 1 biologic therapy for atopic dermatitis such as, dupilumab, tralokinumab or lebrikizumab. Such participants must meet at least 1 of the following conditions: - Participants who stopped treatment due to non-response, partial response, loss of efficacy. - Participants who stopped treatment due to intolerance or AEs. Participants who have had prior exposure to a biologic therapy could have received it in either a marketed setting, or a research setting with documentation of the participants treatment allocation confirming prior exposure to active biologic therapy and not placebo OR • Biologic naive participants: who in addition to an inadequate response to optimization of non-pharmacological measures such as moisturizers, must meet at least 1 of the following conditions: • Participant with a recent history (≤6 months prior to the Screening visit) of inadequate response to a stable regimen of prescription topical medication • Participants for whom prescription topical medications are not tolerated • Participants where there is a concern for potential side effects, such as skin thinning or increased risk of hypothalamic-pituitary-adrenal suppression. Note: Inadequate response to a stable regimen of prescription topical medication (such as medium to high potency TCS or TCI) is defined as failure to achieve and maintain remission or low disease activity state (equivalent to an IGA score =0 [clear] to 2 [mild]) despite treatment for the recommended duration as per label or for the maximum duration recommended for the participant’s treatment, whichever is shorter.
Apply a stable dose of non-medicated topical moisturizer at least twice daily for ≥7 days prior to the baseline visit.
Completed electronic diary entries for PP-NRS for a minimum of 4 of 7 days preceding randomization.

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Exclusion Criteria

History of anaphylaxis as defined by the Sampson Criteria (Sampson, 2006)
History of significant allergies to monoclonal antibodies
Clinically significant multiple or severe drug allergies, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear IgA, dermatosis, toxic epidermal necrolysis or Stevens-Johnson syndrome, and exfoliative dermatitis).
Other types of eczema such as allergic contact dermatitis
Any other concomitant skin disorder (e.g., generalized erythroderma such as Netherton’s Syndrome, or psoriasis), pigmentation, or extensive scarring that in the opinion of the investigator may interfere with the evaluation of AtD lesions or compromise participant safety.
Chronic or acute infection requiring treatment with oral or IV antibiotics, antivirals, anti-protozoal, or antifungals within 4 weeks before the Screening visit or anytime between the Screening and Baseline visits.
Superficial skin infections within 1 week before the Screening visit or active infections (including localized infections), or history of recurrent infections (excluding recurrent fungal infections of the nail bed)
Known, pre-existing or suspected parasitic infection within 6 months before the Screening visit.
Symptomatic herpes zoster within 3 months prior to screening
Uncontrolled hypertension.
Medication or Treatment and Timeframe prior to baseline visit Use of medicated moisturizers (prescribed or over-the-counter) that are likely to impact participant’s AtD - 1 week Herbal or traditional treatments likely to impact participants AtD - 1 week TCS or TCI or topical JAKi - 1 week Systemic corticosteroids, cyclosporine, mycophenolate-mofetil, IFN-γ, azathioprine, methotrexate, or any immunosuppressive therapy - 4 weeks Any biologic treatment for AtD, including but not limited to, dupilumab, tralokinumab, lebrikizumab or nemolizumab - 13 weeks for Dupilumab 15 weeks for Tralokinumab 18 weeks for Lebrikizumab 12 weeks for Nemolizumab For other biologics: 5 half-lives (if known) or 16 weeks, whichever is longer. Specific dermatological treatments include phototherapy, treatment with phototherapy (narrow band ultraviolet B [NBUVB], ultraviolet B [UVB], ultraviolet A1 [UVA1], psoralen + ultraviolet A [PUVA]) - 4 weeks Regular use (more than 2 visits per week) of a tanning booth/parlor - 4 weeks Any investigational drug - 8 weeks or within 5 half-lives (if known), whichever is longer Treatment with a live or live attenuated vaccine - 30 days of the baseline visit or planned to receive such vaccines during the study Any other biologic treatment including but not limited to TNF inhibitors (e.g., etanercept, adalimumab), IL inhibitors (e.g., tocilizumab, anakinra) or T-cell inhibitors (e.g., abatacept) Please note that inclusion of any prior biologic other than those mentioned in Inclusion Criteria #5 should be discussed with the Medical Monitor prior to enrollment - 5 half-lives (if known) or 16 weeks, whichever is longer B Cell-Depleting biologics, including rituximab - 6 months
Uncontrolled chronic disease that might require bursts of oral corticosteroids, e.g., co-morbid severe uncontrolled asthma (defined by an ACQ-5 score ≥1.5 or a history of ≥ 2 asthma exacerbations within the last 12 months requiring systemic [oral and/or parenteral] corticosteroid treatment or hospitalization for > 24 hours).

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Bulgaria	Not Recruiting	07 Feb 2024	7
Czechia	Not Recruiting	07 Feb 2024	6
France	Not Recruiting	07 Feb 2024	8
Germany	Not Recruiting	07 Feb 2024	12
Greece	Not Recruiting	07 Feb 2024	3
Italy	Not Recruiting	07 Feb 2024	13
Poland	Not Recruiting	07 Feb 2024	10
Spain	Not Recruiting	07 Feb 2024	13