Phase 3 Randomized, Double-Blind, Placebo-Controlled Study of Ianalumab in Systemic Lupus Erythematosus Patients on Standard-of-Care Therapy

The primary objective of this study is to demonstrate the superiority of subcutaneous **ianalumab** 300 mg administered monthly, compared to placebo, in achieving the Systemic Lupus Erythematosus Responder Index (SRI-4) at Week 60. This is clinically relevant as achieving SRI-4 is indicative of a significant reduction in disease activity in patients with **Systemic Lupus Erythematosus**, thereby potentially improving patient outcomes and quality of life.

Secondary objectives include:

• Demonstrating the superiority of ianalumab in reducing moderate or severe British Isles Lupus Assessment Group (BILAG) flares up to Week 60.
• Maintaining corticosteroid dose ≤5 mg/day or ≤baseline dose, whichever is lower, between Week 36 and Week 60.
• Achieving BILAG-based Composite Lupus Assessment (BICLA) at Week 60.
• Achieving Lupus Low Disease Activity State (LLDAS) at Week 60.
• Evaluating the time to first occurrence of SRI-4 from baseline up to Week 60.
• Achieving SRI-4 at Week 60 while maintaining a reduced corticosteroid dose ≤5 mg/day or ≤baseline dose, whichever is lower, between Week 36 and Week 60.
• Achieving SRI-6 at Week 60.
• Achieving Short Form 36 (SF-36) Bodily Pain response at Week 60.
• Evaluating the safety and tolerability of ianalumab 300 mg s.c. monthly.
• Evaluating the immunogenicity of ianalumab 300 mg s.c. monthly.
• Characterizing the pharmacokinetics (PK) of ianalumab 300 mg s.c. monthly.

The clinical trial involves a total of **213 participants** diagnosed with **Systemic Lupus Erythematosus** (SLE). The study population includes both male and female subjects, aged 12 years or older, with a specific age restriction of 18 years or older in certain regions. Participants were selected based on their diagnosis of SLE, confirmed by meeting the EULAR/ACR SLE classification criteria at least six months prior to screening. The trial includes individuals with elevated serum titers of Antinuclear Antibodies and those currently receiving corticosteroids, anti-malarial treatment, or other Disease-modifying antirheumatic drugs. Participants must weigh at least 35 kg and have a SLEDAI-2K score of 6 or more, excluding certain symptoms. The trial population is characterized by a diverse age range and includes a vulnerable population, ensuring a comprehensive assessment of the treatment's efficacy across different demographics.

The clinical trial is a **randomized, double-blind, placebo-controlled** Phase 3 study designed to evaluate the efficacy, safety, and tolerability of **ianalumab** in patients with **Systemic Lupus Erythematosus**. The trial aims to demonstrate the superiority of subcutaneous ianalumab 300 mg monthly compared to placebo in achieving the Systemic Lupus Erythematosus Responder Index (SRI-4) at Week 60. The study is expected to run until January 23, 2029, with recruitment having commenced on May 17, 2023. Participants will be involved in the study for a maximum treatment period of 60 weeks.

Study visits are structured to ensure comprehensive monitoring and data collection. The inclusion visit, or screening, will confirm eligibility based on criteria such as age, diagnosis of systemic lupus erythematosus, elevated serum titers of antinuclear antibodies, and current treatment regimens. Follow-up visits will occur regularly to assess the primary endpoint, which is the proportion of participants achieving SRI-4 at Week 60, and secondary endpoints, including the maintenance of reduced corticosteroid doses and the incidence of adverse events. The end-of-study visit will conclude the participant's involvement, ensuring all data is collected and any necessary follow-up care is arranged.

Participants are expected to adhere to the study protocol, with conditions for early termination including non-compliance, withdrawal of consent, or adverse events that compromise safety. The trial will utilize a placebo to VAY736 as a control, with ianalumab administered as a solution for injection in a pre-filled syringe. The study will maintain a rigorous methodology to ensure the reliability and validity of the results, contributing valuable insights into the treatment of systemic lupus erythematosus.

The clinical trial involves the administration of **VAY736**, a solution for injection in a pre-filled syringe, containing the active substance **ianalumab**. This investigational medication is administered subcutaneously at a dosage of 300 mg once monthly. The maximum treatment period is 60 weeks, with a total maximum dose of 4500 mg. The pharmaceutical form is specifically designed for ease of administration, ensuring precise dosing. The active substance, ianalumab, is a protein-based therapeutic agent, classified as a human monoclonal antibody targeting the cytokine receptor BAFF-R. The investigational product is developed and supplied by Novartis Pharma AG.

In addition to the experimental treatment, a **placebo** is utilized as a comparator in this double-blind, placebo-controlled study. The placebo is designed to match the investigational product in appearance and administration route, ensuring blinding integrity. It is administered subcutaneously in the same manner and frequency as VAY736, maintaining consistency in the treatment regimen. The use of placebo allows for the assessment of the efficacy and safety of ianalumab by providing a baseline for comparison. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol and to accurately evaluate the outcomes of the investigational treatment.

The efficacy of the investigational product, **ianalumab**, will be assessed in a randomized, double-blind, placebo-controlled multicenter Phase 3 clinical trial involving patients with Systemic Lupus Erythematosus (SLE). The primary endpoint for evaluating efficacy is the proportion of participants achieving the Systemic Lupus Erythematosus Responder Index (SRI-4) at Week 60. Secondary endpoints include the proportion of participants with no moderate or severe British Isles Lupus Assessment Group flare up to Week 60, maintaining a reduced corticosteroid dose between Week 36 and Week 60, achieving British Isles Lupus Assessment Group-based Composite Lupus Assessment at Week 60, and achieving Lupus Low Disease Activity State at Week 60. Additional secondary endpoints involve the time to first occurrence of SRI-4 from baseline to Week 60, achieving SRI-4 while maintaining a reduced corticosteroid dose, achieving SRI-6, and SF-36 Bodily Pain response at Week 60.

Data collection will occur at specified timepoints, with efficacy parameters measured using validated scales and laboratory tests. The trial will also monitor the incidence and titer of anti-ianalumab antibodies in serum over time, as well as ianalumab concentration in serum during the treatment and follow-up period. The trial aims to demonstrate the superiority of subcutaneous ianalumab 300 mg monthly compared to placebo in achieving the primary endpoint. The study is designed to ensure rigorous assessment of efficacy through comprehensive data collection and analysis, adhering to the highest standards of clinical research.