A multicenter, randomized, double-blind, placebo-controlled, Phase II platform study to assess the efficacy and safety of investigational compound(s) in patients with moderate to severe atopic dermatitis

The primary objective of this study is to establish and characterize the dose-response relationship of the investigational intervention and estimate the treatment effect of targeted dose(s) versus placebo with respect to the percentage change from baseline in Eczema Area and Severity Index (EASI) score at Week 16 in participants with moderate to severe atopic dermatitis. This endpoint is clinically relevant as EASI score reduction represents a validated measure of disease activity and treatment efficacy in atopic dermatitis, providing quantitative assessment of both extent and severity of cutaneous involvement.

The secondary objectives include:

• To establish and characterize the dose-response relationship of the intervention and estimate the targeted dose(s) treatment effect versus placebo with respect to achievement of Investigator's Global Assessment (IGA) response and EASI-75 response at Week 16 in participants with moderate to severe atopic dermatitis. These categorical endpoints provide clinically meaningful thresholds for treatment success, with EASI-75 representing at least 75% improvement from baseline and IGA response indicating clear or almost clear skin status.

• To evaluate the safety and tolerability of the investigational intervention, which is essential for determining the therapeutic index and identifying potential adverse events associated with different dose levels in this patient population.

The clinical trial enrolled a total of **124 participants** diagnosed with **moderate to severe atopic dermatitis**. Both **male** and **female** subjects were included in the study population. The trial recruited **adults** and **elderly** individuals. Participants were required to have a confirmed diagnosis of atopic dermatitis with disease onset of at least one year prior to enrollment. The selection process focused on patients who had demonstrated inadequate response to treatment with **topical medications** or for whom topical treatments were considered medically inadvisable based on investigator judgment. All participants were required to be able and willing to provide informed consent. The study population included **vulnerable populations**. The sponsor did not provide information regarding specific lifestyle considerations such as diet, physical activity, or habits of the participants.

This is a multicenter, randomized, double-blind, placebo-controlled, Phase II platform study evaluating investigational compound(s) in patients with moderate to severe atopic dermatitis. The trial employs a platform design to assess the efficacy and safety of the investigational treatment compared to placebo. Participants will be randomly assigned to receive either the test product **GHZ339**, administered as a **solution for injection** via the **subcutaneous** route, or **placebo to GHZ339**. The study also permits the use of auxiliary medicinal products including **topical corticosteroids** (weak, moderately potent, and potent groups), **tacrolimus**, and **pimecrolimus** as background therapy. The maximum treatment period with GHZ339 is 48 weeks, while auxiliary topical treatments may be used for up to 88 or 100 weeks depending on the specific product.

The primary objective is to establish and characterize the dose-response relationship of the respective intervention and estimate the targeted dose treatment effect versus placebo with respect to the percentage change from baseline on **EASI score** at Week 16 in participants with moderate to severe **atopic dermatitis**. The primary endpoint is the percentage change from baseline in the EASI score at Week 16. Secondary endpoints include **IGA response** at Week 16, defined as an IGA score of 0 (clear) or 1 (almost clear) with at least a 2-point reduction from baseline, **EASI-75 response** at Week 16, defined as a 75% or greater reduction from baseline in EASI score, and safety assessments including treatment emergent **adverse events**, **vital signs**, **ECG**, and laboratory assessments.

Eligible participants must be able and willing to sign the informed consent and have a diagnosis of atopic dermatitis with disease onset for at least 1 year. Participants must present with moderate to severe atopic dermatitis and have a history of inadequate response to treatment with topical medications or for whom topical treatments are medically inadvisable as per investigator judgement. The study is expected to commence recruitment in September 2025 and is estimated to conclude in November 2028, representing an overall trial duration of approximately 3 years.

Participant involvement includes a series of study visits beginning with a screening visit to assess eligibility criteria. Following enrollment, participants will attend scheduled follow-up visits throughout the treatment period to monitor efficacy and safety parameters. The primary efficacy assessment occurs at Week 16, with continued monitoring extending up to 48 weeks for participants receiving GHZ339. An end-of-study visit will be conducted to perform final safety and efficacy evaluations. Early termination from the study may occur under conditions such as withdrawal of consent, significant protocol violations, safety concerns as determined by the investigator, or if continuation is deemed not in the best interest of the participant.

The experimental medication GHZ339 is administered as a solution for injection via the subcutaneous route. GHZ339 contains a protein-derived active substance and is supplied by Novartis Pharma AG. The maximum treatment period for GHZ339 is 48 weeks. The investigational product is designed to assess efficacy and safety in participants with moderate to severe atopic dermatitis.

A matching placebo to GHZ339 is utilized in this double-blind study to maintain blinding and allow for comparison with the active investigational treatment. The placebo is administered in the same manner as the experimental medication to ensure consistency in the study design.

Participants may receive topical corticosteroids as auxiliary therapy during the trial. Weak corticosteroids (Group I) with ATC code D07AA are available for topical application, with a maximum treatment period of 100 weeks. Moderately potent corticosteroids (Group II) with ATC code D07AB are also permitted for topical use, with a maximum treatment period of 100 weeks. Potent corticosteroids (Group III) with ATC code D07AC may be administered topically for up to 88 weeks. These topical corticosteroid treatments serve as standard-of-care therapy options and may be relabeled in selected countries.

Tacrolimus is available as an auxiliary medication for topical administration. This chemical substance with ATC code D11AH01 may be used for a maximum treatment period of 88 weeks. The product may undergo relabeling in selected countries to comply with local regulatory requirements.

Pimecrolimus is provided as an auxiliary treatment option for topical application. This chemical substance with ATC code D11AH02 has a maximum treatment period of 100 weeks. Similar to other auxiliary medications in the study, pimecrolimus may be relabeled in selected countries as needed.

The primary efficacy endpoint is the percentage change from baseline in the Eczema Area and Severity Index (EASI) score at Week 16. Secondary efficacy endpoints include Investigator's Global Assessment (IGA) response at Week 16, defined as an IGA score of 0 (clear) or 1 (almost clear) with at least a 2-point reduction from baseline. Additionally, EASI-75 response at Week 16 will be assessed, which is defined as at least 75% reduction from baseline in EASI score. The study will also evaluate treatment emergent adverse events, vital signs, electrocardiogram findings, and laboratory assessments as part of the overall safety and efficacy evaluation throughout the treatment period.