Efficacy and Safety Evaluation of Anifrolumab in Refractory Chronic and Subacute Cutaneous Lupus Erythematosus: A Phase III Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to evaluate the **efficacy** of anifrolumab compared with placebo on skin manifestations in participants with **Cutaneous Lupus Erythematosus (CLE)** at Week 24. This is clinically relevant as it aims to provide evidence for anifrolumab's potential to improve skin symptoms in CLE, a condition often resistant to standard treatments.

Secondary objectives include:

• Stage 1: Assessing the efficacy of anifrolumab compared with placebo on the early clinical response of skin manifestations at Week 12.
• Stage 1: Evaluating the impact of anifrolumab on skin-related, health-related quality of life at Week 24.
• Stage 1: Evaluating the pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of subcutaneously administered anifrolumab.
• Stage 1: Assessing the safety and tolerability of anifrolumab compared with placebo.
• Stage 2: Demonstrating the superiority of anifrolumab to placebo on skin manifestations at Week 24.
• Stage 2: Demonstrating the superiority of anifrolumab to placebo on the early clinical response of skin manifestations at Week 12.
• Stage 2: Assessing the efficacy of anifrolumab compared with placebo on skin-related, health-related quality of life at Week 24.
• Stage 2: Describing maintained response in disease activity through Week 52.
• Stage 2: Evaluating the PK, PD, and immunogenicity of subcutaneously administered anifrolumab.
• Stage 2: Evaluating the safety and tolerability of anifrolumab compared with placebo.

The clinical trial involves a total of **570 participants** diagnosed with **Cutaneous Lupus Erythematosus** (CLE). The study population includes both male and female subjects, aged between 18 to 70 years. Participants were selected based on a confirmed diagnosis of CLE, with specific clinical and histological criteria, including a CLASI-A total score of at least 10 points. The trial population is characterized by individuals who have shown an inadequate response or intolerance to antimalarial therapy, or have tried other medications for CLE. Participants must have no history of active or latent tuberculosis and must test negative for COVID-19 as per local guidelines. The study includes individuals who are part of a vulnerable population, and contraceptive use is required in accordance with local regulations. The trial does not specify any particular lifestyle considerations such as diet or physical activity.

The clinical trial is a **randomized**, **double-blind**, **placebo-controlled**, Phase III study designed to evaluate the efficacy and safety of **anifrolumab** in adults with **cutaneous lupus erythematosus** (CLE) who are refractory and/or intolerant to antimalarial therapy. The trial is structured in two stages, with the primary objective of assessing the efficacy of anifrolumab compared to placebo on skin manifestations at Week 24. The study is expected to commence recruitment on September 19, 2024, and conclude by December 20, 2027, with a maximum treatment period of 52 weeks.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, confirmed diagnosis of CLE, and prior treatment history. The screening will also include assessments for tuberculosis and COVID-19, as well as documentation of cervical cancer screening for eligible females. Following randomization, participants will receive either anifrolumab or a matching placebo solution via **subcutaneous injection**. Study visits will occur at regular intervals to monitor safety, efficacy, and pharmacokinetic and pharmacodynamic parameters, with primary and secondary endpoints evaluated at Weeks 12 and 24.

The end-of-study visit will mark the conclusion of participant involvement, which is anticipated to last up to 52 weeks. Conditions that may lead to early termination from the study include adverse events, non-compliance with study procedures, or withdrawal of consent. The trial will ensure that all data collected is analyzed to determine the superiority of anifrolumab over placebo in improving skin manifestations in participants with CLE.

The clinical trial involves the administration of **Anifrolumab**, an experimental medication, to evaluate its efficacy and safety in adults with chronic and/or subacute cutaneous lupus erythematosus who are refractory and/or intolerant to antimalarial therapy. **Anifrolumab** is provided as a **solution for injection** and is administered via **subcutaneous injection**. The pharmaceutical form is a pre-filled syringe with a needle safety guard and extended finger flange, ensuring ease of use and safety during administration. The dosing schedule is designed to be consistent, with a maximum treatment period of 52 weeks. The specific dosage in milligrams is not detailed, but the administration is intended to be regular and monitored for compliance throughout the study duration.

In addition to the experimental treatment, a **matching placebo solution for injection** is utilized as a comparator in this double-blind, placebo-controlled study. The placebo is also provided in a pre-filled syringe with a fill volume of 0.8 mL, ensuring that the administration process is identical to that of the active treatment. This placebo is crucial for maintaining the study's integrity by allowing for a direct comparison of the effects of **Anifrolumab** against a non-active substance, thereby enabling the assessment of the drug's true efficacy and safety profile.

The efficacy of **Anifrolumab** in the treatment of Chronic and/or Subacute Cutaneous Lupus Erythematosus (CLE) will be assessed in a multicenter, randomized, double-blind, placebo-controlled, Phase III clinical trial. The primary endpoints for evaluating efficacy include the number of participants achieving a CLA-IGA-R erythema response and a CLASI-70 response at Week 24. These endpoints will be measured to determine the effectiveness of Anifrolumab compared to placebo in improving skin manifestations associated with CLE.

Secondary endpoints will further evaluate efficacy by assessing the number of participants with CLA-IGA-R OMC response, complete response, and follicular activity response at Week 24. Additional assessments include the percent change from baseline in total erythema and scale/hypertrophy scores, as well as changes in Skindex-29+3 domain scores. These parameters will be measured at various timepoints, including Week 12 and Week 24, to provide a comprehensive evaluation of the treatment's impact over time.

Pharmacokinetic (PK) and pharmacodynamic (PD) assessments will be conducted to understand the drug's behavior in the body, and the immunogenicity of subcutaneously administered Anifrolumab will be evaluated. The trial will also monitor the number of participants experiencing adverse events to ensure safety alongside efficacy assessments. The study is designed to demonstrate the superiority of Anifrolumab over placebo in participants who are refractory and/or intolerant to antimalarial therapy, with a maximum treatment period of 52 weeks.