Long-Term Safety and Efficacy Evaluation of Litifilimab (BIIB059) in Adults with Active Subacute or Chronic Cutaneous Lupus Erythematosus

The primary objective of this study is to evaluate the long-term **safety** and **tolerability** of BIIB059 (litifilimab) in participants who have completed the parent study 230LE301 (NCT05531565). These participants have active subacute cutaneous lupus erythematosus (CLE) and/or chronic CLE, with or without systemic manifestations, and are refractory and/or intolerant to antimalarial therapy. This objective is clinically relevant as it aims to ensure the continued safety of litifilimab, a critical consideration for patients with CLE who have limited treatment options due to intolerance or resistance to standard therapies.

Secondary objectives include:

• Evaluating the long-term effect of litifilimab on disease activity in participants with active subacute CLE and/or chronic CLE.
• Assessing the effect of litifilimab in preventing disease damage in these participants.
• Evaluating the long-term effect of litifilimab on preventing lupus flare in participants with CLE with systemic lupus erythematosus (SLE).
• Assessing the long-term use of oral corticosteroids in participants receiving litifilimab treatment.
• Evaluating the impact of litifilimab on participant-reported health-related quality of life (HRQoL).
• Assessing the long-term effect of litifilimab on laboratory parameters.
• Evaluating the immunogenicity of litifilimab.
• Assessing the pharmacokinetics (PK) of litifilimab.

The clinical trial involves a total of **118 participants** who have completed the parent study 230LE301. The study population includes both **male and female** subjects, with an age range that encompasses adults and older adults. Participants are individuals with active **subacute cutaneous lupus erythematosus (CLE)** and/or chronic CLE, with or without systemic manifestations, who are refractory and/or intolerant to antimalarial therapy. The trial population was selected based on their completion of the parent study, ensuring they received treatment through Week 48 and attended the final assessment at Week 52. The study includes a vulnerable population, indicating that special considerations are in place to protect these participants. Lifestyle factors such as diet, physical activity, and habits are not specified in the available data. The trial aims to evaluate the long-term safety and tolerability of BIIB059 (litifilimab) in this specific cohort.

The clinical trial is designed as a **long-term extension study** to evaluate the continuous safety and efficacy of **litifilimab** (BIIB059) in adult participants with active subacute cutaneous lupus erythematosus and/or chronic cutaneous lupus erythematosus, with or without systemic manifestations, who are refractory and/or intolerant to antimalarial therapy. This study is a single-arm, open-label, Phase 3 trial, which follows participants who have completed the parent study 230LE301. The primary objective is to assess the long-term safety and tolerability of BIIB059, with secondary endpoints focusing on various efficacy measures, including improvements in disease activity scores and quality of life assessments.

The trial is expected to last up to 128 weeks, with participant involvement beginning from the completion of the parent study and continuing through the end of the extension study. Participants will receive **subcutaneous injections** of BIIB059, with the maximum treatment period set at 104 weeks. The study will include several key visits: an initial inclusion (screening) visit to confirm eligibility, regular follow-up visits to monitor safety and efficacy, and an end-of-study visit to assess final outcomes. The inclusion criteria require participants to have completed the parent study on treatment and to provide informed consent. There are no specific exclusion criteria listed.

Participants may be withdrawn from the study early if they experience significant adverse events or if they choose to withdraw consent. The primary endpoint is the number of participants with treatment-emergent adverse events and serious adverse events, while secondary endpoints include various measures of disease activity improvement and quality of life changes. The study aims to provide comprehensive data on the long-term use of BIIB059 in this patient population, contributing valuable insights into its safety and efficacy profile.

The clinical trial involves the administration of **BIIB059**, an experimental medication developed by Biogen Idec Research Limited. The active substance in BIIB059 is **litifilimab**, a protein-based compound. The pharmaceutical form of BIIB059 is an **injection**, specifically designed for subcutaneous administration. The trial is structured as a long-term extension study, with a maximum treatment period of 104 weeks. The dosing regimen for BIIB059 is not explicitly detailed in terms of milligrams per day or total dose, as the maximum daily and total dose amounts are indicated as zero, suggesting that the dosing schedule may be determined based on individual participant needs or other study-specific criteria.

In this study, BIIB059 is the sole investigational product, and no additional non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are utilized. The trial focuses on participants with active subacute cutaneous lupus erythematosus (CLE) and/or chronic CLE, with or without systemic manifestations, who are refractory and/or intolerant to antimalarial therapy. Participant compliance with the treatment regimen is monitored throughout the study, although specific compliance monitoring methods are not detailed in the provided data. The study aims to evaluate the long-term safety and tolerability of BIIB059 in the specified patient population.

The efficacy of BIIB059 (litifilimab) in the clinical trial will be assessed using several parameters. The primary endpoint focuses on the number of participants experiencing treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) over a time frame of up to 128 weeks. Secondary endpoints include the percentage of participants achieving various levels of improvement in the Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity Score (CLASI-A) from the baseline value of the parent study. These improvements are categorized as CLASI-70, CLASI-50, and CLASI-90 responses, indicating 70%, 50%, and 90% improvements, respectively. Additionally, the Cutaneous Lupus Activity of Physician's Global Assessment-Revised (CLA-IGA-R) scores for erythema and other morphologic characteristics will be evaluated, with scores of 0 or 1 indicating significant improvement.

The cumulative duration of sustained responses, defined by the number of weeks with specified improvements in CLASI-A and CLA-IGA-R scores, will also be measured. The trial will assess changes in quality of life using validated instruments such as the Cutaneous Lupus Erythematosus – Quality of Life (CLE-QoL) and the European Quality of Life – 5-Dimensions Questionnaire, 3-Level Version (EQ-5D-3L) at specified time points, including baseline, week 52, and week 104. Additional assessments include changes in the 36-Item Short Form Survey (SF-36), Work Productivity and Activity Impairment (WPAI): Lupus, and Patient Health Questionnaire-9 (PHQ-9) at the same intervals.

Serum concentration of **litifilimab** and the presence of anti-BIIB059 antibodies in serum will be monitored up to 128 weeks. The trial will also track changes in standard laboratory parameters and ECG results to identify any clinically relevant changes from baseline. These efficacy assessments will be conducted at various time points throughout the study, ensuring a comprehensive evaluation of the long-term efficacy of BIIB059 in participants with active subacute or chronic cutaneous lupus erythematosus.