Efficacy and Safety Evaluation of Litifilimab in Active Subacute and Chronic Cutaneous Lupus Erythematosus Refractory to Antimalarial Therapy

The primary objective of this study is to evaluate the **efficacy** of BIIB059 compared with placebo in reducing skin disease activity in participants with active Subacute Cutaneous Lupus Erythematosus (SCLE) and/or Chronic Cutaneous Lupus Erythematosus (CCLE), with or without systemic manifestations, who are refractory and/or intolerant to antimalarials. This is measured by the Cutaneous Lupus Activity of Physician's Global Assessment-Revised (CLA-IGA-R) score in Parts A and B (US) and the Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) score in Part B (ROW). The clinical relevance of this objective lies in addressing the unmet need for effective treatments in patients who do not respond to or cannot tolerate standard antimalarial therapy.

The secondary objectives of the study are to evaluate the efficacy of BIIB059 in reducing SCLE and/or CCLE disease activity by CLA-IGA-R and CLASI-A; to assess additional efficacy parameters of BIIB059 in reducing SCLE and/or CCLE disease activity; and to evaluate the safety, tolerability, and immunogenicity of BIIB059 in Parts A and B of the study. These objectives aim to provide a comprehensive understanding of the therapeutic potential and safety profile of BIIB059 in this patient population.

The clinical trial involves a total of **170 participants** diagnosed with **Subacute Cutaneous Lupus Erythematosus** or **Chronic Cutaneous Lupus Erythematosus**. The study population includes both male and female subjects, with an age range encompassing adults and adolescents. Participants were selected based on specific criteria, including a histologically confirmed diagnosis of cutaneous lupus erythematosus (CLE) with or without systemic manifestations, and the presence of active cutaneous manifestations that meet the study's criteria. The trial does not include a vulnerable population. Participants are required to have a Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) score of 10 or higher and must exhibit active CLE lesions despite an adequate trial of antimalarial treatment. Lifestyle considerations such as diet, physical activity, and habits are not specified in the available data.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy and safety of BIIB059 in participants with active **Subacute Cutaneous Lupus Erythematosus** and/or **Chronic Cutaneous Lupus Erythematosus**. The trial is structured in two parts: Part A (Phase 2) and Part B (Phase 3), and it is conducted across multiple centers. The study aims to assess the reduction in skin disease activity using the Cutaneous Lupus Activity of Physician's Global Assessment-Revised (CLA-IGA-R) score and the Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) score. The trial is expected to last until December 2027, with participant recruitment having commenced in February 2022.

Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on criteria such as a histologically confirmed diagnosis of cutaneous lupus erythematosus and active cutaneous manifestations. The inclusion criteria also require a CLASI-A score of 10 or higher and an active lesion despite antimalarial treatment. Following the screening, participants will be randomized to receive either BIIB059 or a placebo, administered via subcutaneous injection. The study includes multiple follow-up visits to monitor efficacy and safety, with primary endpoints assessed at Week 16 and Week 24, and secondary endpoints evaluated up to Week 52. The end-of-study visit will conclude the participant's involvement, which is anticipated to last up to 76 weeks, depending on the treatment phase and response.

Participants may be withdrawn from the study early if they experience significant adverse events, fail to adhere to the study protocol, or if the investigator deems it necessary for their safety. The trial's primary endpoints include the percentage of participants achieving a CLA-IGA-R erythema score of 0 or 1 and a CLASI-70 response, defined as a 70% decrease in CLASI-A score from baseline. Secondary endpoints involve various measures of improvement in skin disease activity and quality of life assessments. The study is not classified as low intervention, emphasizing its focus on investigating the safety and efficacy of BIIB059 as a potential therapy for cutaneous lupus erythematosus.

The clinical trial involves the administration of **BIIB059**, an experimental medication, which is a sterile liquid formulated for **injection**. The active substance in BIIB059 is **litifilimab**, a protein-based compound. The medication is administered via the **subcutaneous** route. The dosing schedule is designed to ensure participant safety and compliance, with a maximum treatment period of 52 weeks. The specific dosage in milligrams is not detailed in the provided data. Participant compliance will be monitored throughout the study to ensure adherence to the dosing regimen.

In addition to the experimental treatment, a **placebo** is utilized as a comparator in this double-blind study. The placebo is also a sterile liquid for injection, with a formulation composition identical to that of BIIB059, minus the active ingredient. This ensures that any observed effects can be attributed to the active substance, litifilimab, rather than the injection process or formulation components. The placebo is administered via the same subcutaneous route as BIIB059, maintaining consistency in administration methods across study groups.

The efficacy of BIIB059 in the treatment of active Subacute Cutaneous Lupus Erythematosus (SCLE) and/or Chronic Cutaneous Lupus Erythematosus (CCLE) will be assessed through a series of primary and secondary endpoints. The primary endpoints include the percentage of participants achieving a Cutaneous Lupus Activity of Physician's Global Assessment-Revised (CLA-IGA-R) erythema score of 0 or 1 at Week 16 for Parts A and B (US), and a Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-70) response, defined as a ≥70% decrease in CLASI-A score from baseline to Week 24 for Part B (ROW).

Secondary endpoints will evaluate additional measures of efficacy, such as the percentage of participants achieving a CLASI-50 response, defined as a ≥50% decrease in CLASI-A score from baseline at Weeks 16 and 24, and changes from baseline in the Cutaneous Lupus Erythematosus Disease Area and Severity Index Damage (CLASI-D) score up to Week 52. Other secondary measures include changes in the Cutaneous Lupus Erythematosus-Quality of Life (CLE-QoL) score and the Dermatology Life Quality Index (DLQI) score at specified time points. Efficacy assessments will be conducted using validated scales and scores, with data collection scheduled at various timepoints throughout the study, including Weeks 16, 24, and 52.