A Phase 3, 24-week, Randomized, Placebo-controlled, Double-blind Study to Assess the Efficacy, Safety and Tolerability of Rocatinlimab (AMG 451) Monotherapy in Adult Subjects With Moderate-to-severe Atopic Dermatitis (AD) (ROCKET-Ignite)

The primary objective of this study is to evaluate the **efficacy** of rocatinlimab compared with placebo at week 24 in adult subjects with moderate-to-severe **atopic dermatitis**. This assessment will be conducted using the Validated Investigator’s Global Assessment for Atopic Dermatitis (vIGA-AD™) and the Eczema Area and Severity Index (EASI). The clinical relevance of this objective lies in determining the potential of rocatinlimab as a therapeutic option for managing atopic dermatitis, a condition characterized by chronic inflammation and significant impact on quality of life.

Secondary objectives include:

• Evaluating the efficacy of rocatinlimab compared with placebo at week 16, assessed using EASI and vIGA-AD.
• Assessing the efficacy of rocatinlimab at week 16 and week 24 on the patient-reported outcome (PRO) measure of pruritus.
• Evaluating the efficacy at week 24 using vIGA-AD with an additional assessment of morphology.
• Assessing the efficacy at week 24 on the PRO measure of atopic dermatitis skin pain.
• Evaluating the efficacy on facial and hand atopic dermatitis at week 24.

These secondary objectives aim to provide a comprehensive understanding of rocatinlimab's impact on various aspects of atopic dermatitis, including symptom severity, patient-reported outcomes, and specific anatomical sites, thereby contributing to a holistic evaluation of its therapeutic potential.

The clinical trial involves a total of **458 participants** diagnosed with **Atopic Dermatitis**. The study population includes both male and female subjects aged 18 years and older, or the legal adult age within the participant's country, whichever is older. Participants were selected based on a history of inadequate response to topical treatments or when such treatments are medically inadvisable due to significant side effects or safety concerns. The trial specifically targets individuals with moderate-to-severe atopic dermatitis, as defined by an Eczema Area and Severity Index (EASI) score of 16 or higher, a Validated Investigator’s Global Assessment for Atopic Dermatitis (vIGA-AD) score of 3 or higher, and at least 10% body surface area involvement. Additionally, participants must report a worst pruritus Numerical Rating Scale (NRS) score of 4 or higher. The trial includes a vulnerable population, ensuring comprehensive representation of the affected demographic. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is a **Phase 3**, 24-week, randomized, placebo-controlled, double-blind study designed to assess the efficacy, safety, and tolerability of **rocatinlimab** monotherapy in adult subjects with moderate-to-severe **atopic dermatitis**. The trial aims to evaluate the efficacy of rocatinlimab compared with placebo at week 24, using the Validated Investigator’s Global Assessment for Atopic Dermatitis (vIGA-AD™) and the Eczema Area and Severity Index (EASI). The primary endpoints include achieving a vIGA-AD score of 0 (clear) or 1 (almost clear) with a ≥ 2-point reduction from baseline at week 24, and achieving a ≥ 75% reduction from baseline in EASI score at week 24. Secondary endpoints involve achieving EASI 75 and vIGA-AD 0/1 at week 16, among other measures.

The trial will involve a sequence of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis of atopic dermatitis, and history of inadequate response to topical treatments. Participants must have moderate-to-severe atopic dermatitis at both the initial screening and day 1 pre-randomization visit, defined by specific EASI and vIGA-AD scores, and a minimum body surface area involvement. Following the screening, participants will be randomized to receive either rocatinlimab or placebo, administered via subcutaneous injection. Follow-up visits will occur at regular intervals to monitor efficacy and safety, with assessments conducted at weeks 16 and 24. The end-of-study visit will conclude the trial, with final evaluations of the primary and secondary endpoints.

The expected length of participant involvement is approximately 24 weeks, aligning with the trial's duration. Conditions that may lead to early termination from the study include adverse events, withdrawal of consent, or any situation where continued participation is deemed medically inadvisable. The trial is not categorized as low intervention and is scheduled to conclude by March 31, 2025, with recruitment having commenced on April 21, 2023.

The clinical trial involves the administration of **Rocatinlimab**, a solution for injection, as the experimental medication. Rocatinlimab, also known by its sponsor product code AMG 451, is a protein-based therapeutic agent developed by Amgen Inc. The pharmaceutical form of Rocatinlimab is a solution intended for subcutaneous use. The dosing regimen allows for a maximum daily dose of 9999 mg, with a total treatment period extending up to 24 weeks. The administration schedule and specific dosing intervals are determined by the study protocol, ensuring adherence to the trial's objectives. Participant compliance with the dosing schedule is monitored throughout the study to ensure accurate assessment of the drug's efficacy and safety.

The study also includes a **placebo** control, which is presented in identical containers and stored in the same manner as Rocatinlimab to maintain blinding. The placebo is administered via the same subcutaneous route as the experimental drug. This placebo control is crucial for evaluating the true efficacy of Rocatinlimab by providing a baseline for comparison. The placebo does not contain any active pharmaceutical ingredients and is used to ensure that any observed effects can be attributed to the experimental treatment rather than psychological or other non-specific factors. Compliance with placebo administration is similarly monitored to maintain the integrity of the trial results.

The efficacy of rocatinlimab in the treatment of moderate-to-severe **Atopic Dermatitis** will be assessed in a Phase 3, 24-week, randomized, placebo-controlled, double-blind clinical trial. The primary endpoints for evaluating efficacy include achieving a Validated Investigator’s Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0 (clear) or 1 (almost clear) with a ≥ 2-point reduction from baseline at week 24, and achieving a ≥ 75% reduction from baseline in the Eczema Area and Severity Index (EASI 75) score at week 24.

Secondary endpoints will include achieving EASI 75 and vIGA-AD 0/1 at week 16, achieving a ≥ 90% reduction from baseline in EASI score (EASI 90) at week 24, and improvements in patient-reported outcomes such as the weekly average of daily worst pruritus numeric rating scale (NRS) score and AD skin pain NRS score at week 24. Additionally, achieving clear skin at week 24 for subjects with hand AD at baseline and achieving a vIGA-AD 1 response with only barely perceptible erythema or vIGA-AD 0 response at week 24 will be evaluated.

The efficacy assessments will be conducted using validated scales such as the vIGA-AD and EASI, with measurements taken at specified timepoints, including weeks 16 and 24. Patient-reported outcomes will be collected to assess pruritus and skin pain, providing a comprehensive evaluation of the treatment's impact on the disease and patient quality of life.