Long-term Safety and Tolerability Assessment of Ianalumab in Systemic Lupus Erythematosus: A Randomized, Double-blind, Placebo-controlled Extension Study

The primary objective of this study is to evaluate the long-term **safety** and tolerability of ianalumab 300 mg administered subcutaneously (s.c.) either monthly or quarterly in participants with active **Systemic Lupus Erythematosus** (SLE). This is clinically relevant as it aims to ensure that the treatment regimen is safe for long-term use in managing this chronic autoimmune disease, which can significantly impact patients' quality of life.

Secondary objectives include:

• Evaluating the long-term efficacy of ianalumab 300 mg administered s.c. monthly or quarterly.
• Assessing the effect of ianalumab 300 mg on the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index.
• Evaluating the impact of ianalumab 300 mg on corticosteroids intake.
• Assessing the effect of ianalumab 300 mg on British Isles Assessment Group (BILAG) flares.

These secondary objectives are crucial for understanding the broader therapeutic benefits of ianalumab, including its potential to reduce disease damage, decrease reliance on corticosteroids, and manage disease flares, thereby improving overall patient outcomes in SLE management.

The clinical trial involves a total of **452 participants** diagnosed with **Systemic Lupus Erythematosus** (SLE). The study population includes both male and female subjects, with an age range that encompasses both adults and adolescents. Participants were selected based on their prior involvement in one of the two SIRIUS-SLE core studies and their completion of the treatment period through Week 60 without discontinuation. The trial does not specifically target a vulnerable population. Participants are expected to have a general health status that allows them to benefit clinically from continued study treatment. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data. The selection criteria ensure that participants have provided informed consent, with additional consent required for those reaching the age of consent during the study.

The clinical trial is designed as a **randomized, double-blind, placebo-controlled** extension study to evaluate the long-term safety and tolerability of **ianalumab** in patients with **systemic lupus erythematosus**. The trial will involve the administration of ianalumab at a dose of 300 mg, delivered subcutaneously either monthly or quarterly. The study is expected to span a duration of approximately 7 years, with an estimated end date in December 2031. Participants will be involved in the study for a maximum treatment period of 36 months.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility is confirmed based on criteria such as prior participation in the SIRIUS-SLE core studies and completion of the treatment period through Week 60 without discontinuation. Following the screening, participants will undergo regular follow-up visits to monitor the incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), as well as to assess secondary endpoints such as the proportion of participants achieving SRI-4 response and changes in the SLICC/ACR Damage Index. The end-of-study visit will conclude the participant's involvement, ensuring all safety and efficacy data are collected.

Participants may be subject to early termination from the study if they experience significant adverse events or if, in the judgment of the investigator, they no longer clinically benefit from continued study treatment. The trial's primary objective is to ensure the long-term safety and tolerability of ianalumab, with secondary objectives focusing on efficacy measures and the impact on disease activity and damage indices. The study will adhere to rigorous methodological standards to ensure the reliability and validity of the findings.

The clinical trial involves the administration of **ianalumab**, marketed under the product name VAY736, which is provided as a **solution for injection in a pre-filled syringe**. This experimental medication is administered via the **subcutaneous** route. The dosage is set at 300 mg, with the administration frequency being either monthly or quarterly, depending on the study arm. The maximum treatment period for ianalumab is 36 months, with a total maximum dose of 11,700 mg. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.

In addition to the experimental treatment, a **placebo** is used as a comparator in the study. The placebo is designed to match the pharmaceutical form of VAY736, although specific details regarding its composition are not provided. The placebo is administered in a manner consistent with the experimental treatment to maintain the double-blind nature of the trial.

Several non-experimental treatments are also included in the study. **Tenofovir alafenamide** is administered orally in a pharmaceutical form denoted as PHF00082MIG. The maximum daily dose is 25 mg, with a total maximum dose of 27,000 mg over a 36-month period. **Entecavir** is another oral medication included in the trial, with a maximum daily dose of 0.5 mg and a total maximum dose of 540 mg over the same treatment period. Additionally, **emtricitabine** combined with **tenofovir disoproxil** is administered orally, with a maximum daily dose of 300 mg and a total maximum dose of 328,500 mg over 36 months. These medications are used as auxiliary treatments and are monitored for participant compliance.

Lastly, the trial includes a category of **glucocorticoids**, although specific details regarding the active substances, dosage, and administration route are not provided. The glucocorticoids are classified under the ATC code H02AB and are used for a maximum treatment period of one month. The administration route is listed as unknown, and the dosage form is unspecified. These treatments are included to support the overall management of the participants' condition during the trial.

Efficacy in the clinical trial will be assessed using several secondary endpoints. These include the proportion of participants who achieve a Systemic Lupus Erythematosus Responder Index (SRI-4) response up to Week 216, the change from baseline in the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index up to Week 216, the average daily dose of oral corticosteroids administered up to Week 216, and the annualized British Isles Lupus Assessment Group (BILAG) moderate or severe flare rate up to Week 216. These parameters will be measured and collected at specified timepoints throughout the study duration to evaluate the efficacy of **ianalumab** in patients with systemic lupus erythematosus. The analysis will be conducted using validated scales and instruments appropriate for each endpoint, ensuring the reliability and accuracy of the efficacy assessments.