Evaluation of Long-term Safety and Efficacy of Enpatoran in Subacute Cutaneous, Discoid, and Systemic Lupus Erythematosus Post-WILLOW Study Completion

The primary objective of this study is to evaluate the **long-term safety** and tolerability of **enpatoran** in participants with Subacute Cutaneous Lupus Erythematosus (SCLE), Discoid Lupus Erythematosus (DLE), and/or Systemic Lupus Erythematosus (SLE). This is clinically relevant as it aims to ensure that enpatoran, a potential therapeutic agent, can be safely administered over an extended period, which is crucial for chronic conditions such as lupus erythematosus.

Secondary objectives include:

• To further assess the long-term safety and tolerability of enpatoran in participants with SCLE, DLE, and/or SLE.

The clinical trial involves a total of **202 participants** diagnosed with **systemic lupus erythematosus (SLE)** and **cutaneous lupus erythematosus (CLE)**. The study population includes both male and female subjects, aged between 18 and 76 years. Participants were selected based on their completion of the 24-week Treatment of the Willow Study, with active SCLE, DLE, and/or SLE. The trial does not include a vulnerable population. Participants are required to have a Body Mass Index (BMI) of 40 kg/m² or higher at screening. The selection process ensures that individuals who have successfully completed Week 48 of Part 1 are eligible for participation in the long-term extension (LTE) Part 2, with some exceptions based on sponsor review. The trial does not specify any particular lifestyle considerations such as diet or physical activity.

The clinical trial is a **Phase 2**, double-blind, dose-ranging, parallel, long-term extension study designed to evaluate the safety and efficacy of **Enpatoran** in participants with **systemic lupus erythematosus (SLE)** and **cutaneous lupus erythematosus (CLE)**. The trial is structured to include two parts, with the primary objective of assessing the long-term safety and tolerability of Enpatoran. The study employs a randomized, double-blind, controlled design, ensuring that neither the participants nor the investigators are aware of the treatment assignments, which include Enpatoran and a placebo. The trial is expected to span from January 2023 to August 2028, with participant involvement potentially lasting up to 48 weeks.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, completion of a prior study, and body mass index. Following successful screening, participants will be randomized to receive either Enpatoran or placebo. Regular follow-up visits will be scheduled to monitor safety, collect data on treatment-emergent adverse events, and assess laboratory parameters. The end-of-study visit will conclude the participant's involvement, during which final assessments will be conducted to evaluate the overall safety profile.

Participant involvement is expected to last up to 48 weeks, with the possibility of early termination if adverse events occur or if the participant withdraws consent. The study will also consider early termination for participants who do not adhere to the protocol or if the sponsor deems it necessary for safety reasons. The trial's primary endpoints focus on the incidence of treatment-emergent adverse events, serious adverse events, and adverse events of special interest, while secondary endpoints include the number of participants with laboratory abnormalities and QT interval corrections. The trial is not classified as low intervention and is conducted under the sponsorship of Merck Healthcare KGaA.

The clinical trial involves the administration of **Enpatoran**, an experimental medication, to evaluate its safety and efficacy in participants with Subacute Cutaneous Lupus Erythematosus, Discoid Lupus Erythematosus, and/or Systemic Lupus Erythematosus. **Enpatoran** is provided in the form of a **film-coated tablet** and is intended for **oral use**. The active substance, **Enpatoran**, is of chemical origin. The trial is designed to assess the long-term safety and tolerability of the medication over a maximum treatment period of 48 weeks. The specific dosage and frequency of administration are not detailed in the provided data.

In addition to the experimental treatment, the study includes the use of a **placebo** as a comparator. The **Enpatoran Placebo** is utilized to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments. The placebo is designed to mimic the appearance of the **Enpatoran** film-coated tablet but does not contain the active substance. The administration route and form of the placebo are not specified in the data provided.

The efficacy of **Enpatoran** in the clinical trial will be assessed through a series of predefined endpoints. The primary endpoints focus on the safety profile, evaluated by the incidence of Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs) in both Part 1 and Part 2 of the study. Secondary endpoints include the number of participants with abnormalities in laboratory parameters and QT interval corrected. These assessments will be conducted throughout the trial to ensure comprehensive monitoring of the participants' responses to the treatment.