A Phase 3, Randomized, 24-week, Placebo-controlled, Double-blind Study to Assess the Efficacy, Safety, and Tolerability of Rocatinlimab (AMG 451) in Combination With Topical Corticosteroids and/or Topical Calcineurin Inhibitors in Adult Subjects With Moderate-to-severe Atopic Dermatitis (AD) (ROCKET-SHUTTLE)

The primary objective of this phase 3 study is to evaluate the efficacy of rocatinlimab in combination with topical corticosteroids and/or topical calcineurin inhibitors compared to placebo combined with these topical therapies in adult subjects with moderate-to-severe atopic dermatitis. Clinical efficacy is primarily assessed at week 24 using the Validated Investigator’s Global Assessment for Atopic Dermatitis (vIGA-AD) and the Eczema Area and Severity Index (EASI). 5

Secondary objectives include:

• Evaluation of efficacy at week 16 using EASI and vIGA-AD.
• Assessment of patient-reported outcomes (PRO) regarding pruritus at weeks 16 and 24.
• Evaluation of patient-reported skin pain at week 24.
• Assessment of efficacy in specific anatomical regions, including facial atopic dermatitis and hand atopic dermatitis at week 24.
• Evaluation of efficacy at week 24 using EASI.

This clinical trial involves a total of 408 patients diagnosed with atopic dermatitis. The study population includes both males and females within the specified age ranges. Eligible participants must have a history of the condition for at least 12 months and have demonstrated an inadequate response to medium or higher potency topical corticosteroids. Inclusion requires the presence of moderate-to-severe disease, defined by an Eczema Area and Severity Index score of $\ge$ 16, a validated Investigator’s Global Assessment for Atopic Dermatitis score of $\ge$ 3, and involvement of at least 10% body surface area. Additionally, a patient-reported pruritus numeric rating scale score of $\ge$ 4 is required at screening. The primary objectives are:

• To evaluate the efficacy of rocatinlimab in combination with topical corticosteroid and/or topical calcineurin inhibitor compared with placebo in combination with those agents at week 24.
• To assess efficacy using the specified clinical indices at week 24.

This Phase 3, randomized, double-blind, placebo-controlled study is designed to evaluate the efficacy, safety, and tolerability of rocatinlimab in combination with topical corticosteroids and/or topical calcineurin inhibitors in adults with moderate-to-severe atopic dermatitis. The investigation compares rocatinlimab administered via subcutaneous injection against a placebo, both used alongside background topical therapies. The study duration is 24 weeks. The clinical sequence begins with a screening visit to assess eligibility based on criteria such as a history of inadequate response to medium or higher potency corticosteroids, a minimum EASI score of 16, a vIGA-AD score of 3 or higher, and at least 10% body surface area involvement. Following a prerandomization visit, subjects receive the study interventions. Primary efficacy endpoints assessed at week 24 include the proportion of subjects achieving clear or almost clear skin via vIGA-AD and a 75% improvement in eczema via EASI. Secondary endpoints include assessments of pruritus, skin pain, and facial or hand involvement. Participant involvement is expected to last for the 24-week treatment period.

Rocatinlimab is an experimental medication administered as a solution for injection. The drug is delivered via subcutaneous route at a dosage of 9999 mg.

The control group receives a placebo for AMG 451.

Background therapy includes the use of topical corticosteroids at a dose of 1 unit and topical calcineurin inhibitors, classified as immunosuppressive agents, at a dose of 2 units. These are administered via a topical route.

Efficacy is assessed in subjects with atopic dermatitis through several primary endpoints at week 24. The primary evaluation includes the proportion of subjects achieving clear or almost clear skin as determined by the validated Investigator’s Global Assessment for Atopic Dermatitis (vIGA-AD). Additionally, the proportion of subjects achieving a 75% improvement in the Eczema Area and Severity Index (EASI) from baseline is measured at week 24.

Secondary efficacy parameters include:

• Achievement of EASI 75 or vIGA-AD 0/1 at week 16.
• Changes from baseline in the weekly average of the daily worst pruritus numeric rating scale (NRS) score at week 16 and week 24.
• Achievement of EASI 90 at week 24.
• Change from baseline in the weekly average of the daily AD skin pain NRS score at week 24.
• Achievement of a vIGA-AD response with only barely perceptible erythema or a vIGA-AD 0 response at week 24.
• Achievement of a clear Facial AD Severity Score at week 24 for subjects with facial involvement at baseline.
• Achievement of a clear Hand AD Severity Score at week 24 for subjects with hand involvement at baseline.