Long-term Safety and Efficacy of Abrocitinib in Moderate to Severe Atopic Dermatitis: A Phase 3 Multicenter Extension Study

The primary objective of this study is to estimate the long-term **safety** of 100 mg and 200 mg once daily (QD) of **abrocitinib**, with or without topical treatments, in adult and adolescent subjects who previously participated in qualifying abrocitinib atopic dermatitis trials. This is clinically relevant as it aims to ensure the continued safety of abrocitinib, a JAK1 inhibitor, for patients with moderate to severe atopic dermatitis, a chronic inflammatory skin condition that significantly impacts quality of life.

Secondary objectives include:

• Estimating the long-term efficacy of abrocitinib, which is crucial for understanding the sustained therapeutic benefits of the drug in managing atopic dermatitis symptoms over an extended period.
• Evaluating the potential effect of abrocitinib on adolescent growth, which is important to assess any impact on developmental parameters in younger patients receiving the treatment.

The clinical trial involves a total of **1945 participants** who are being studied to assess the long-term safety of abrocitinib in individuals with **moderate to severe atopic dermatitis**. The study population includes both male and female subjects aged 12 years and older, with a specific focus on those who have previously participated in qualifying abrocitinib trials. Participants are required to have completed the full treatment or rescue treatment period of a qualifying parent study. The trial includes adolescents, but only if approved by the relevant regulatory authorities. The participants are expected to comply with scheduled visits, treatment plans, and laboratory tests. Lifestyle considerations include avoiding prolonged sun exposure and the use of tanning booths or ultraviolet light sources. The trial population was selected based on their previous involvement in related studies and their ability to adhere to the study's requirements. The study does not specify any particular dietary or physical activity requirements for participants.

The clinical trial is a **Phase III** multicenter, long-term extension study designed to evaluate the efficacy and safety of **abrocitinib** in subjects aged 12 years and older with moderate to severe **atopic dermatitis**. The trial employs a randomized, double-blind, controlled design to ensure the reliability and validity of the results. Participants will be administered either 100 mg or 200 mg of abrocitinib once daily, with or without topical treatments, over a maximum treatment period of 92 days. The trial is expected to conclude by January 31, 2026, with recruitment having commenced on March 5, 2018.

The study involves a sequence of visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, previous participation in qualifying abrocitinib trials, and the ability to comply with study procedures. Follow-up visits will be scheduled to monitor the incidence of treatment-emergent adverse events, serious adverse events, and any clinical abnormalities. These visits will also assess changes from baseline in clinical laboratory values, electrocardiogram measurements, and vital signs. The end-of-study visit will evaluate the overall safety and efficacy outcomes, including the Investigator's Global Assessment score and improvements in the Eczema Area and Severity Index.

Participant involvement is expected to last for the duration of the treatment period, with conditions for early termination including the occurrence of serious adverse events or non-compliance with study protocols. The study aims to provide comprehensive data on the long-term safety and efficacy of abrocitinib, contributing valuable insights into its use for treating moderate to severe atopic dermatitis.

The clinical trial involves the administration of **Cibinqo 100 mg film-coated tablets**, which contain the active substance **abrocitinib**. Abrocitinib is a **JAK1 inhibitor** and is chemically derived. The pharmaceutical form of the medication is a film-coated tablet, designed for **oral use**. The tablets are administered once daily, with a maximum daily dose of 200 mg. The treatment period extends up to 92 days. The clinical tablets differ in appearance from the commercial product, being round and white, as opposed to the commercial version which is round, pink, and debossed with "ABR 100" on one side and "PFE" on the other. Participant compliance with the dosing schedule is monitored throughout the study.

The study also includes a **placebo** group, where participants receive a placebo designed to match the **Cibinqo 100 mg tablet** in appearance. The placebo is administered in the same manner as the active treatment, ensuring blinding of the study. The placebo is used to assess the efficacy and safety of abrocitinib by providing a comparator for the active treatment group. The placebo tablets are also administered orally once daily, with the same treatment duration of up to 92 days. Compliance with the placebo administration is similarly monitored to ensure adherence to the study protocol.

Efficacy in this clinical trial will be assessed using a range of primary and secondary endpoints. The primary endpoints focus on safety, including the incidence of treatment-emergent adverse events, serious adverse events, and adverse events leading to discontinuation, as well as clinical abnormalities and changes from baseline in clinical laboratory values, electrocardiogram (ECG) measurements, and vital signs.

Secondary efficacy endpoints will evaluate the therapeutic impact of **abrocitinib** in subjects with moderate to severe atopic dermatitis. These include achieving an Investigator's Global Assessment (IGA) score of clear (0) or almost clear (1) with a reduction from baseline of ≥ 2 points, and improvements in the Eczema Area and Severity Index (EASI) scores (EASI-50, EASI-75, EASI-90, and EASI-100). Additional measures include a ≥ 4-point improvement in the severity of pruritus NRS, changes in the frequency of itching, Patient Global Assessment (PtGA), percentage Body Surface Area (BSA) affected, Dermatology Life Quality Index (DLQI) or Children's DLQI (CDLQI), Patient Oriented Eczema Measure (POEM), Hospital Anxiety and Depression Scale (HADS), and EuroQol Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) or Youth Scale (EQ-5D-Y). The trial will also assess steroid-free days, serum hsCRP levels, changes in height standard deviation score, and the proportion of abnormal bone findings in knee MRI in adolescent subjects exposed to abrocitinib.

These efficacy parameters will be measured at all scheduled time points throughout the trial, with baseline defined as pre-dose Day 1 in the relevant qualifying Parent study. The assessments will utilize validated scales and instruments to ensure accurate and reliable data collection and analysis.