Evaluation of Long-Term Safety and Efficacy of Litifilimab in Adults with Active Systemic Lupus Erythematosus: A Phase 3 Multicenter, Randomized, Dose-Blind Study

The primary objective of this study is to evaluate the long-term **safety** and tolerability of **litifilimab** in participants with active systemic lupus erythematosus (SLE). This is clinically relevant as it aims to ensure that the treatment is safe for prolonged use, which is crucial for managing a chronic condition like SLE.

Secondary objectives include:

• Evaluating the long-term effect of litifilimab on disease activity in participants with SLE.
• Assessing the ability of litifilimab to maintain low disease activity in SLE patients over time.
• Investigating the effect of litifilimab in preventing irreversible organ damage in participants with active 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 Questionnaire (HRQoL), symptoms, and impacts of SLE.
• Assessing the long-term effect of litifilimab on laboratory parameters.
• Evaluating the immunogenicity of litifilimab.

The clinical trial involves a total of **669 participants** diagnosed with **systemic lupus erythematosus** (SLE). The study population includes both male and female subjects, with an age range that spans from young adults to older adults. Participants were selected based on their completion of one of the 52-week double-blind placebo-controlled parent Phase 3 studies, specifically those who received either litifilimab or placebo and attended the final study assessment visit at Week 52. The trial does not focus on a vulnerable population, and participants are expected to have a general health status that allows them to understand the study's purpose and risks, provide informed consent, and comply with privacy regulations. Lifestyle considerations such as diet and physical activity are not specified, but women of childbearing potential are required to practice highly effective contraception during the study and for a specified period afterward. The trial does not include any vulnerable populations, ensuring a focus on individuals who can fully comprehend and consent to the study's requirements.

The clinical trial is designed to evaluate the long-term safety and tolerability of **litifilimab** in adult participants with active **systemic lupus erythematosus** (SLE). This is a multicenter, randomized, dose-blind, Phase 3 long-term extension study. The trial involves the administration of **BIIB059** via subcutaneous injection, with a placebo group receiving an identical formulation minus the active ingredient. The study is expected to run from July 2022 to March 2029, with a maximum treatment period of 156 weeks for each participant.

Participants eligible for inclusion are those who have completed one of the 52-week double-blind placebo-controlled parent Phase 3 studies and have attended the last study assessment visit. The primary endpoints include the incidence of treatment-emergent adverse events (TEAEs) and the number of serious adverse events (SAEs). Secondary endpoints focus on various clinical response measures, including the Systemic Lupus Erythematosus Responder Index (SRI-4), Joint-50 response, and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) responses, among others.

The trial consists of several key study visits. The initial inclusion visit serves as a screening to confirm eligibility based on the completion of prior studies and other criteria. Follow-up visits are scheduled to monitor safety, efficacy, and any adverse events, with assessments conducted at regular intervals. The end-of-study visit marks the conclusion of the participant's involvement, where final evaluations are performed. Participants are expected to remain in the study for the full duration unless conditions arise that necessitate early termination, such as significant adverse events or withdrawal of consent.

Participant involvement is expected to last up to 156 weeks, with conditions for early termination including the occurrence of severe adverse events or the participant's decision to withdraw consent. The study is conducted in accordance with ethical guidelines and regulatory requirements, ensuring the confidentiality and safety of all participants throughout the trial duration.

The clinical trial involves the administration of **BIIB059**, an experimental medication, to evaluate its long-term safety and efficacy in adult participants with active **Systemic Lupus Erythematosus (SLE)**. BIIB059, also known by its active substance name **litifilimab**, is a protein-based therapeutic agent. It is formulated as an injection for **subcutaneous use**. The dosing regimen for BIIB059 is determined by the study protocol, with a maximum treatment period of 156 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 in the study as a comparator. The placebo is a sterile liquid for injection, designed to mimic the formulation of BIIB059, excluding the active ingredient. This ensures that the placebo is indistinguishable from the active treatment in terms of appearance and administration. The placebo is administered via the same route as BIIB059, maintaining the study's blind design. The use of a placebo allows for the assessment of BIIB059's efficacy and safety by providing a control group for comparison. The study does not include any other non-experimental treatments or standard-of-care therapies as part of the trial protocol.

The efficacy of the investigational product, **litifilimab**, in the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints focus on safety, specifically the incidence of Treatment Emergent Adverse Events (TEAEs) and the number of Serious Adverse Events (SAEs). Secondary endpoints are designed to evaluate the therapeutic efficacy of litifilimab in participants with active Systemic Lupus Erythematosus (SLE). These include the proportion of participants achieving an SRI-4 response, Joint-50 response, and various CLASI responses by visit. Additionally, the study will assess the proportion of participants achieving a BICLA response by visit 4, the annualized severe SFI Flare Rate, and the percentage of time spent in LLDAS 5.

Further secondary endpoints include the proportion of participants with sustained LLDAS, the duration of sustained LLDAS, annual change from baseline in SDI score, and cumulative exposure to OCS over time. The study will also measure the proportion of participants with OCS ≤ 7.5 mg and ≤ 5 mg by visit. Participant-reported outcome measures will be collected using tools such as LupusQoL, SF-36 (Acute Version), EQ-5D-3L, FACIT-Fatigue, PHQ-9, WPAI:Lupus, and PtGA. Changes in standard laboratory parameters and ECG results will be monitored, along with the incidence of antibodies to litifilimab. These assessments will be conducted at specified visits throughout the trial to ensure comprehensive evaluation of the drug's efficacy and safety profile.