Long-term Safety and Efficacy Assessment of Ianalumab in Sjögren’s Syndrome: A Randomized, Double-blind, Two-arm NEPTUNUS Extension Study

The primary objective of this study is to assess the long-term **safety** and tolerability of ianalumab in participants with Sjögren’s syndrome. This is clinically relevant as it aims to ensure that the therapeutic use of ianalumab is safe for prolonged periods, which is crucial for managing a chronic condition like Sjögren’s syndrome.

Secondary objectives include:

• Evaluating the long-term efficacy of ianalumab 300 mg administered monthly or every 3 months.
• Demonstrating the comparability of ianalumab Ctrough between different pre-filled syringe configurations for participants on continuous monthly treatment.
• Further assessing the pharmacokinetics of ianalumab.
• Assessing the impact of long-term treatment on B-cell depletion.

The clinical trial involves a total of **475 participants** diagnosed with **Sjögren’s syndrome**. The study population includes both male and female subjects, with an age range encompassing adults and older adults. Participants were selected based on their prior involvement in one of the two NEPTUNUS core studies, specifically CVAY736A2301 or CVAY736A2302, and must have completed the entire treatment up to Week 48 without discontinuation. The trial does not include a vulnerable population. The selection criteria ensure that participants are expected to clinically benefit from continued ianalumab therapy. The study does not specify any particular lifestyle considerations such as diet or physical activity.

The clinical trial is designed as a **randomized, double-blind, controlled** study to evaluate the long-term safety and efficacy of **ianalumab** in patients with **Sjögren’s syndrome**. The trial is an extension study following the NEPTUNUS core studies, with an estimated duration extending until January 6, 2031. Participants are required to have completed the core studies up to Week 48 without treatment discontinuation and must be expected to benefit clinically from continued ianalumab therapy. The primary endpoint is the incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), while secondary endpoints include changes in ESSDAI and ESSPRI scores, meaningful improvement in SSSD scores, and **ianalumab** serum concentrations.

The trial involves a sequence of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on the principal inclusion criteria. Participants will then undergo regular follow-up visits to monitor safety and efficacy parameters, including B-cell count measurements and serum concentration assessments. The end-of-study visit will conclude the participant's involvement, ensuring all necessary data is collected and any remaining safety assessments are completed. The expected length of participant involvement is up to 204 weeks, with conditions for early termination including withdrawal of consent, adverse events, or any other reason deemed necessary by the investigator.

Participants will receive either the investigational product or a placebo, administered via **subcutaneous** injection, with a maximum daily dose of 300 mg and a total dose not exceeding 10,800 mg over the treatment period. The trial is not categorized as low intervention and is classified as a Phase 3 trial. The study aims to provide comprehensive data on the long-term use of **ianalumab** in managing **Sjögren’s syndrome**, contributing valuable insights into its safety profile and therapeutic potential.

The clinical trial involves the administration of several treatments, including both experimental and non-experimental medications. **Ianalumab**, marketed under the name VAY736, is the primary experimental medication. It is provided as a **solution for injection** in either a pre-filled syringe or pen. The administration route is **subcutaneous**, with a maximum daily dose of 300 mg and a total maximum dose of 10,800 mg over a treatment period of 36 weeks. This medication is not a paediatric formulation and is classified as a protein of other origin.

**Lamivudine** is used as an auxiliary treatment in the trial. It is administered orally in a pharmaceutical form identified as PHF00169MIG. The maximum daily dose is 100 mg, with a total maximum dose of 106,400 mg over a 38-week period. Lamivudine is a chemical substance and is not formulated for paediatric use.

Another auxiliary treatment is a combination of **Emtricitabine** and **Tenofovir Disoproxil**, administered orally in the form PHF00082MIG. The maximum daily dose is 50 mg, with a total maximum dose of 54,000 mg over 36 weeks. Both active substances are of chemical origin and are not paediatric formulations.

**Tenofovir Alafenamide** is also included as an auxiliary treatment. It is administered orally with a maximum daily dose of 25 mg and a total maximum dose of 27,000 mg over 36 weeks. This chemical substance is not formulated for paediatric use.

**Entecavir** is another auxiliary treatment, administered orally in the form PHF00082MIG. The maximum daily dose is 0.5 mg, with a total maximum dose of 540 mg over 36 weeks. Entecavir is a chemical substance and is not a paediatric formulation.

The trial also includes a **placebo** to VAY736, provided as a solution for injection in either a pre-filled pen or syringe. The placebo is used to maintain the double-blind nature of the study. The administration schedule and dosing for the placebo match those of the active VAY736 treatment.

The efficacy of ianalumab in patients with **Sjögren's syndrome** will be assessed through several secondary endpoints. These include the change from baseline in the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) and the proportion of participants achieving a reduction of at least 1 point or a 15% reduction from baseline in the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) score over time, up to Week 204. Additionally, the proportion of participants achieving meaningful improvement in the Sjögren's Syndrome Symptom Diary (SSSD) score over time, up to Week 204, will be evaluated. Ianalumab serum concentrations will be collected pre-dose (Ctrough) at Week 48 from core studies and at Week 64, as well as during treatment and follow-up after the last dose. B-cell count measurements will also be conducted as part of the efficacy assessment.