A Phase 2b, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess the Efficacy, Safety, and Tolerability of IMVT-1402 in Adult Participants with Primary Sjogren’s Disease with Moderate to Severe Systemic Disease Activity

The primary objective of this study is to evaluate the efficacy of IMVT-1402 administered subcutaneously once weekly compared to placebo in adult participants with primary Sjögren's disease presenting moderate to severe systemic disease activity. Efficacy assessment is based on the clinical ESSDAI score (EULAR Sjögren's Syndrome Disease Activity Index), a validated instrument for measuring systemic disease activity in Sjögren's disease. This evaluation is clinically relevant as it addresses the need for effective therapeutic options in patients with significant systemic manifestations of primary Sjögren's disease, a chronic autoimmune disorder characterized by lymphocytic infiltration of exocrine glands and potential multisystem involvement. IMVT-1402 is a monoclonal antibody targeting the FcRn receptor, and the study investigates its potential to reduce pathogenic autoantibody levels and ameliorate disease activity in this patient population.

This clinical trial enrolled a total of **108 participants** diagnosed with **primary Sjögren's disease**. The study population included both **male and female subjects** classified as **adults** and **elderly patients**. Participants were required to have an established diagnosis of primary Sjögren's disease for at least 12 months prior to screening and meet the 2016 ACR/EULAR classification criteria for this condition. Eligible subjects demonstrated moderate to severe systemic disease activity, defined by a **clinESSDAI total score** of 5 or greater at screening. All participants were **seropositive** for antibodies to **SSA/Ro** and maintained residual salivary function, evidenced by a stimulated whole salivary flow rate of at least 0.01 mL/min. The trial did not involve vulnerable populations. The sponsor did not provide specific information regarding lifestyle considerations such as diet, physical activity, or habits.

This is a Phase 2b, multicenter, **randomized**, **double-blind**, **placebo-controlled**, parallel-group clinical trial designed to evaluate the efficacy, safety, and tolerability of **IMVT-1402** in adult participants with **Primary Sjogren's Disease** presenting with moderate to severe systemic disease activity. The investigational medicinal product IMVT-1402 is a solution for injection containing **imeroprubart**, a human IgG1 monoclonal antibody against FcRn receptor, administered via **subcutaneous** route. Participants will be randomized to receive either IMVT-1402 or matching placebo. The maximum daily dose is 600 mg, with a maximum total dose of 28,800 mg administered over a treatment period of up to 48 weeks. The primary objective is to evaluate the efficacy of IMVT-1402 compared to placebo as assessed by **clinESSDAI score**, with the primary endpoint being the change from baseline in clinESSDAI score at Week 24.

Eligible participants must have a diagnosis of primary Sjogren's Disease for at least 12 months prior to the screening visit and meet the 2016 ACR/EULAR classification criteria for Primary Sjogren's Syndrome. Participants must demonstrate moderate to severe systemic disease activity with a clinESSDAI total score of at least 5 at screening. Additional inclusion criteria require participants to be seropositive for antibodies to **SSA/Ro** and have residual salivary flow as measured by a **stimulated whole salivary flow rate** of at least 0.01 mL/min at the screening visit. The trial is expected to commence recruitment in November 2025 and is estimated to conclude in February 2028.

The study involves a structured series of visits beginning with a screening visit to assess eligibility and establish baseline measurements. Following successful screening and enrollment, participants will attend regular follow-up visits throughout the treatment period to monitor efficacy, safety, and tolerability. The primary efficacy assessment will occur at Week 24, with continued monitoring extending through the maximum treatment period of 48 weeks. An end-of-study visit will be conducted to perform final safety and efficacy evaluations. The total duration of participant involvement will span the treatment period plus any required follow-up assessments. Participants may be withdrawn from the study early due to safety concerns, lack of efficacy, withdrawal of consent, protocol violations, or at the discretion of the investigator if continued participation is not in the participant's best interest.

**IMVT-1402** is the experimental medication under investigation in this clinical trial. The active substance is **imeroprubart**, a human IgG1 monoclonal antibody against the FcRn receptor. The product is manufactured by Immunovant Sciences GmbH and is classified as a protein of other origin. IMVT-1402 is supplied as a **solution for injection** and is administered via the **subcutaneous route**. The dosing regimen consists of **weekly administration** with a maximum daily dose of **600 mg**. The maximum total dose over the treatment period is **28,800 mg**, corresponding to a maximum treatment duration of **48 weeks**. The investigational medicinal product is delivered using a device for administration, though the device does not bear a CE mark. This formulation is not specifically developed as a paediatric formulation.

A **placebo** is used as the comparator treatment in this study. The placebo is identical in appearance to IMVT-1402 but contains no active substance. The placebo serves as the control arm in this randomized, double-blind, placebo-controlled trial design to enable assessment of the efficacy, safety, and tolerability of the experimental medication. Participants assigned to the placebo group will receive the inactive formulation following the same administration schedule as those receiving the active treatment to maintain blinding throughout the study.

Efficacy will be assessed using the clinESSDAI score as the primary parameter. The primary endpoint is the change from baseline in clinESSDAI score at Week 24. The clinESSDAI score is used to evaluate moderate to severe systemic disease activity in participants with primary Sjögren's disease. At the Screening Visit, participants must have a clinESSDAI total score of 5 or greater to be eligible for enrollment. The study compares IMVT-1402 administered subcutaneously once weekly to placebo in terms of efficacy based on this validated assessment tool.