A Multicenter, Randomized, Double-Blind, Placebo-Controlled, 2-Stage Trial to Evaluate Efficacy and Safety of Telitacicept Compared to Placebo in Patients with Moderately to Severely Active Systemic Lupus Erythematosus (REMESLE-1)

The primary objective of this study is to evaluate the **efficacy**, safety, pharmacokinetics (PK), and pharmacodynamics (PD) of telitacicept at doses of 160 mg and 240 mg, administered as a subcutaneous injection via prefilled syringes weekly for 52 weeks in adult patients with moderately to severely active Systemic Lupus Erythematosus (SLE) who are receiving standard of care (SoC) treatment. This is clinically relevant as it aims to determine the potential of telitacicept to improve disease management in patients with SLE, a chronic autoimmune condition characterized by systemic inflammation and multi-organ involvement.

Secondary objectives include:

• Stage 1: To evaluate the efficacy of telitacicept (160 mg and 240 mg) compared to placebo over 24 weeks in patients with an inadequate response to SoC SLE treatment.
• Stage 2: To assess the efficacy of telitacicept at Week 24 in patients with an inadequate response to SoC therapy.
• Stage 2: To evaluate the glucocorticoid (GC) sparing effect of telitacicept when added to SoC therapy.
• Stage 2: To assess the efficacy of telitacicept in reducing SLE flares when added to SoC therapy.
• Stage 2: To evaluate the GC sparing effect and improvement in disease activity when telitacicept is added to SoC therapy.
• Stage 2: To assess the efficacy of telitacicept measured by at least partial improvement in all organ systems active at baseline when added to SoC therapy.

The clinical trial involves a total of **298 participants** diagnosed with **Moderately to Severely Active Systemic Lupus Erythematosus**. The study population includes both male and female adults, with an age range that encompasses individuals from young adulthood to middle age. Participants were selected based on their diagnosis of systemic lupus erythematosus (SLE) for at least six months prior to the screening visit, and they must have a clinical SLEDAI score of 4 or higher at Day 0 prior to randomization. Additionally, participants are required to have at least one positive serologic parameter within the screening period and must be currently receiving at least one standard of care (SoC) SLE therapy, such as oral glucocorticoids, antimalarial, and/or immunosuppressive agents. The trial includes a vulnerable population, indicating that special considerations are in place to ensure the safety and ethical treatment of all participants. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the **efficacy** and safety of **telitacicept** in patients with moderately to severely active systemic lupus erythematosus. This is a multicenter, randomized, double-blind, placebo-controlled, two-stage trial. The trial will involve the administration of telitacicept at doses of 160 mg and 240 mg via subcutaneous injection using pre-filled syringes. The trial is expected to last for 52 weeks, with the estimated end date in April 2026.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a diagnosis of systemic lupus erythematosus for at least six months and a clinical SLEDAI score of ≥ 4. Following randomization, participants will receive either telitacicept or a placebo. The primary endpoint for Stage 1 is the proportion of patients achieving a response in an SLE Responder Index (SRI-4) at Week 52, while Stage 2 focuses on the efficacy of telitacicept at Week 52 in subjects with an inadequate response to standard of care therapy.

Follow-up visits will occur regularly throughout the trial to monitor safety, tolerability, and pharmacokinetics/pharmacodynamics of the treatment. The end-of-study visit will assess the final outcomes and any long-term effects of the treatment. Participant involvement is expected to last the full 52 weeks unless early termination is warranted due to adverse events, withdrawal of consent, or non-compliance with the study protocol.

The clinical trial involves the administration of **Telitacicept**, a protein-based experimental medication, formulated as a **solution for injection in pre-filled syringe**. The active substance, **telitacicept**, is produced by REMEGEN CO. LTD. and is classified under the origin category "Protein - Other". The medication is administered via **subcutaneous injection**. Participants receive either 160 mg or 240 mg of telitacicept weekly, with a maximum daily dose of 240 mg and a cumulative dose not exceeding 12,480 mg over the course of the 52-week treatment period. The pre-filled syringe is designed as a single-use device, ensuring the integrity and sterility of the medication for each administration.

The trial also includes a **placebo** group, where participants receive a placebo designed to match the telitacicept injection in appearance and administration method. The placebo is used to maintain the double-blind nature of the study, ensuring that neither the participants nor the investigators are aware of the treatment assignments. This placebo is administered in the same manner as the telitacicept, via subcutaneous injection, to provide a consistent experience across all study groups.

Throughout the trial, participants continue to receive standard-of-care (SOC) therapy for **Systemic Lupus Erythematosus (SLE)**, which is not specified in the trial data but is assumed to be consistent with current medical guidelines for the management of SLE. Compliance with the dosing schedule is monitored to ensure adherence to the treatment protocol, and any deviations are documented for further analysis. The trial aims to evaluate the efficacy and safety of telitacicept in comparison to the placebo, with a focus on patients with moderately to severely active SLE who have shown an inadequate response to SOC therapy.

The efficacy of Telitacicept in the treatment of **Systemic Lupus Erythematosus (SLE)** will be assessed through a multicenter, randomized, double-blind, placebo-controlled, 2-stage clinical trial. The primary endpoint for Stage 1 is the proportion of patients achieving a response in the SLE Responder Index (SRI-4) at Week 52. For Stage 2, the primary endpoint is also the proportion of subjects achieving an SRI-4 response at Week 52. Secondary endpoints include the proportion of adult patients achieving an SRI-4 response at Week 24 in Stage 1, and in Stage 2, the proportion of subjects achieving a BILAG-based Combined Lupus Assessment (BICLA) response at Week 52, among others.

Measurements will be collected at specified timepoints, including Week 24, Week 40, and Week 52, using validated scales such as the SLE Responder Index and BILAG-based Combined Lupus Assessment. The trial will also evaluate the time to flare assessed by the SFI from baseline through Week 52. The efficacy assessments will be conducted in adult patients with moderately to severely active SLE who have an inadequate response to standard of care (SoC) therapy. The trial will involve the administration of Telitacicept 160 mg and 240 mg as a subcutaneous injection via prefilled syringes weekly for 52 weeks.