A Phase 3, Multicenter, Double-blind Maintenance Study to Assess Long-term Safety, Tolerability, and Efficacy of Rocatinlimab in Adult and Adolescent Subjects With Moderate-to-severe Atopic Dermatitis (AD) (ROCKET-ASCEND)

The primary objective of this study is to describe the long-term safety and tolerability of rocatinlimab in subjects with moderate-to-severe atopic dermatitis. This evaluation is clinically relevant for establishing the extended safety profile of rocatinlimab treatment in this patient population, which is essential for understanding the risk-benefit ratio during prolonged therapeutic exposure.

The secondary objective is to describe the maintenance of response of each rocatinlimab treatment group compared with placebo among responders to rocatinlimab in adult monotherapy studies. This assessment provides insight into the durability of therapeutic response and the comparative efficacy of continued rocatinlimab treatment versus placebo in maintaining clinical improvement achieved during initial therapy.

This long-term extension clinical trial enrolled a total of **1,585 participants** diagnosed with **atopic dermatitis**. The study population included both **male** and **female** subjects across multiple age categories, encompassing **adolescents**, **adults**, and **elderly** individuals. Participants were selected based on their completion of a parent rocatinlimab study, with those from parent study 20210263 required to demonstrate a specified improvement in **EASI score** by Week 52. The trial population was classified as a **patient population** and included **vulnerable populations**. The study aimed to evaluate the long-term safety and tolerability of rocatinlimab in subjects with **moderate-to-severe** atopic dermatitis. No additional information regarding lifestyle considerations, general health status, or other demographic characteristics was provided by the sponsor.

This is a Phase 3, multicenter, double-blind maintenance study designed to evaluate the long-term safety, tolerability, and efficacy of **rocatinlimab** in adult and adolescent subjects with moderate-to-severe **atopic dermatitis**. The trial employs a **randomized**, **double-blind**, **controlled** design comparing rocatinlimab with **placebo**. The investigational medicinal product rocatinlimab (AMG 451) is administered as a **solution for injection** via **subcutaneous use**, while the control group receives placebo for AMG 451. The estimated recruitment start date is October 2023, with the estimated end date in February 2027, indicating a total trial duration of approximately three and a half years.

The primary objective is to describe the long-term safety and tolerability of rocatinlimab in subjects with moderate-to-severe atopic dermatitis. The **primary endpoint** consists of **treatment-emergent adverse events**, including clinically significant changes in laboratory values and vital signs, as well as **serious adverse events**. Secondary endpoints focus on maintaining clinical response among subjects who achieved specific efficacy measures at day 1, including maintaining **vIGA-AD** 0/1 response, maintaining revised **IGA** (rIGA) 0/1 response, maintaining **EASI 75** response, maintaining combined vIGA-AD 0/1 and EASI 75 response, and maintaining reduction from parent study baseline in worst pruritus **NRS score**.

Eligible subjects must have completed an end of treatment duration visit in a rocatinlimab parent study. Subjects enrolled from parent study 20210263 are required to have achieved an improvement in EASI score by a specified amount at Week 52. The study includes a screening visit to assess eligibility criteria, followed by a series of scheduled follow-up visits throughout the maintenance period to monitor safety parameters and efficacy outcomes. An end-of-study visit will be conducted to complete all final assessments and evaluations. The expected length of participant involvement extends throughout the maintenance period, with the duration determined by the overall trial timeline and individual treatment response.

Conditions that may lead to early termination from the study include the occurrence of unacceptable adverse events, withdrawal of consent, protocol violations, investigator decision based on safety concerns, or other circumstances that preclude continued participation. Throughout the study, subjects will be monitored for adverse events and changes in clinical status to ensure participant safety and data integrity.

**Rocatinlimab** (sponsor product code **AMG 451**) is the experimental medication being evaluated in this clinical trial. Rocatinlimab is a protein-based therapeutic agent containing the **active substance** rocatinlimab. The product is manufactured by AMGEN INC and is supplied as a **solution for injection**. The **route of administration** is **subcutaneous use**. The formulation is not specifically designed as a paediatric formulation. The maximum daily dose amount is 9999 milligrams, and the maximum total dose amount is 9999 milligrams, with a maximum treatment period of 9999 days. The specific dosing frequency and detailed dosing schedules will be determined according to the study protocol for subjects with moderate-to-severe **atopic dermatitis**.

**Placebo for AMG 451** serves as the comparator treatment in this double-blind maintenance study. The placebo is formulated to match the experimental medication to maintain blinding throughout the trial. No active pharmaceutical ingredients are present in the placebo formulation. The pharmaceutical form, route of administration, and dosing schedule of the placebo will correspond to those of rocatinlimab to ensure consistency in treatment administration between study arms. The placebo is not a paediatric formulation.

The study is designed as a multicenter, double-blind trial, which requires that both investigators and subjects remain unaware of treatment assignment throughout the study duration. Participant compliance monitoring will be implemented according to standard clinical trial procedures to ensure adherence to the prescribed dosing regimen and to capture any deviations from the protocol. The long-term safety, tolerability, and efficacy of rocatinlimab will be assessed in adult and adolescent subjects throughout the maintenance phase of treatment.

The primary efficacy endpoint focuses on the assessment of treatment-emergent adverse events, including clinically significant changes in laboratory values and vital signs, as well as serious adverse events. Secondary efficacy endpoints evaluate the maintenance of clinical response among subjects who achieved specific thresholds at day 1. These include maintaining vIGA-AD 0/1 response among subjects achieving vIGA-AD 0/1 response at day 1, maintaining revised IGA (rIGA) 0/1 response among subjects achieving rIGA 0/1 response at day 1, and maintaining EASI 75 response among subjects achieving EASI 75 response at day 1. Additional secondary endpoints assess the maintenance of combined vIGA-AD 0/1 response and EASI 75 response among subjects who achieved both responses at day 1, as well as maintaining reduction from parent study baseline in worst pruritus NRS score among subjects who achieved such reduction at day 1.