A Phase 2, Multicenter, Multinational, Randomized, Double-blind, Placebo-controlled Study to Assess the Safety, Efficacy, and Pharmacokinetics of Multiple Dose Levels of ESK-001 in Adult Patients with Systemic Lupus Erythematosus

The primary objective of this study is to evaluate the effect of **ESK-001** on disease activity in patients with **systemic lupus erythematosus**. This is measured by the proportion of patients achieving a response based on the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) at week 48, comparing different doses of ESK-001 to placebo. This objective is clinically relevant as it aims to determine the efficacy of ESK-001 in reducing disease activity, which is crucial for improving patient outcomes in systemic lupus erythematosus.

Secondary objectives include assessing the safety and tolerability of multiple dose levels of ESK-001. These evaluations are essential to ensure that the treatment is not only effective but also safe for long-term use in patients.

The clinical trial involves a total of **273 participants** diagnosed with **systemic lupus erythematosus**. The study population includes both male and female subjects, aged between 18 to 70 years, with a body mass index ranging from 18 to 40 kg/m² and a total body weight exceeding 40 kg. Participants were selected based on their ability and willingness to provide informed consent and comply with the study protocol. The trial includes individuals with adequate peripheral venous access and a clinical SLEDAI-2K score of at least 4 points, indicating skin involvement. Participants are required to be on a stable dose of oral corticosteroids, antimalarial treatment, or no more than one conventional DMARD. The study population is characterized by a diverse range of lifestyle factors, including the use of specific medications as part of their treatment regimen. The trial does not exclude vulnerable populations, ensuring a comprehensive assessment of the investigational product's safety and efficacy across a broad demographic.

The clinical trial is a **Phase 2**, multicenter, multinational, randomized, double-blind, placebo-controlled study designed to evaluate the safety, efficacy, and pharmacokinetics of multiple dose levels of ESK-001 in adult patients diagnosed with **systemic lupus erythematosus**. The trial is structured into two parts: Part A aims to compare the effect on disease activity, measured by the proportion of patients achieving a BILAG-based Composite Lupus Assessment (BICLA) response at week 48 between doses of ESK-001 and placebo. Part B focuses on assessing the safety and tolerability of ESK-001 at a single dose. The trial is expected to conclude by March 31, 2027, with recruitment starting on September 30, 2023.

Participants will be involved in the study for a maximum treatment period of 48 weeks. The study visits are sequenced as follows: an initial inclusion (screening) visit to confirm eligibility based on criteria such as age, body mass index, and a confirmed diagnosis of systemic lupus erythematosus. This is followed by regular follow-up visits to monitor safety, efficacy, and pharmacokinetics, and an end-of-study visit to assess the final outcomes. The primary endpoint is defined by meeting all criteria as described in the study protocol, while secondary endpoints include the incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), along with assessments of vital signs, physical examinations, 12-lead ECGs, and clinical laboratory tests.

Participants are expected to comply with all study requirements, and conditions that may lead to early termination from the study include non-compliance with the protocol, withdrawal of consent, or any adverse event that poses a risk to the participant's health. The study involves the administration of ESK-001 and a placebo, both in tablet form, with the route of administration being oral. The trial is not classified as a low-intervention study, and it does not involve a pediatric formulation. The study is conducted under the sponsorship of ALUMIS INC., with the investigational product being ESK-001, a chemical substance.

The clinical trial involves the administration of **ESK-001**, an investigational medication, in the form of a tablet. The active substance, also named ESK-001, is of chemical origin and is provided by ALUMIS INC. The pharmaceutical form of ESK-001 is a tablet, intended for **oral use**. The trial is designed to evaluate multiple dose levels of ESK-001, with a maximum treatment period of 48 weeks. The specific dosage and frequency of administration are not detailed in the provided data. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the protocol.

In addition to the experimental treatment, a **placebo** is utilized as a comparator in this double-blind, placebo-controlled study. The placebo is also administered in tablet form, though specific details regarding its composition and administration are not provided. The use of a placebo is critical in assessing the efficacy and safety of ESK-001 by providing a baseline for comparison. The trial aims to measure the effect of ESK-001 on disease activity in patients with **Systemic Lupus Erythematosus** by comparing outcomes between the active treatment and placebo groups.

Efficacy in this clinical trial will be assessed by evaluating the effect of ESK-001 on disease activity in adult patients with **Systemic Lupus Erythematosus**. The primary efficacy endpoint is the proportion of patients achieving a response based on the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) at week 48. This endpoint will be measured by comparing the response rates between different doses of ESK-001 and placebo. The assessment will be conducted at the end of the 48-week treatment period.