A Phase 3 Randomized Controlled Trial to Evaluate the Efficacy and Safety of Rilzabrutinib in Adults with Active IgG4-Related Disease

The primary objective is to evaluate the efficacy of rilzabrutinib in prolonging the flare-free period in adults with active IgG4-related disease. The secondary objectives include:

• Evaluation of the clinical flare-free rate.
• Assessment of disease activity control.
• Determination of the requirement for glucocorticoids to maintain clinical stability.
• Evaluation of safety and tolerability profiles.

This study involves a total of 94 patients, including both males and females, within the age ranges of 3 to 4. The study population consists of individuals diagnosed with IgG4-related disease. Key inclusion requirements involve an adjudicated clinical diagnosis meeting the 2019 ACR/EULAR classification criteria with a total score of 20 or greater. Participants must exhibit active disease in at least one organ system, excluding lymph nodes, characterized by an IgG4-RD Responder Index total activity score of 2 or more. Additionally, subjects must have a history or current involvement of at least one organ or site affected by the condition and must have maintained stable glucocorticoid dosing for a minimum of 2 weeks prior to screening. Inclusion also necessitates a willingness to undergo glucocorticoid tapering and to participate in repeated imaging procedures, such as computed tomography, magnetic resonance imaging, positron emission tomography, or ultrasound. Participants are required to maintain an up-to-date vaccination status and utilize contraception consistent with local regulations.

This Phase 3, randomized, double-blind, placebo-controlled study is designed to evaluate the efficacy and safety of rilzabrutinib in adult participants diagnosed with active IgG4-related disease. The primary objective is to assess the time to the first adjudicated clinical disease flare compared to a placebo. The total study duration is 52 weeks. The research methodology includes a screening visit to confirm an adjudicated clinical diagnosis and ensure participants meet specific classification criteria, including a minimum IgG4-RD Responder Index activity score. Following screening, participants will undergo a blinded treatment period. During this time, participants must be on a stable dose of glucocorticoids and must be willing to undergo a taper. Assessment of the disease involves repeated imaging procedures, such as computed tomography, magnetic resonance imaging, positron emission tomography, or ultrasound. The study will monitor secondary endpoints, including complete remission rates, annualized rate of flares, and cumulative glucocorticoid doses. Safety is monitored through the evaluation of treatment-emergent adverse events, serious adverse events, and potential abnormalities in laboratory tests, vital signs, or electrocardiograms.

The experimental treatment consists of rilzabrutinib (SAR444671). The specific pharmaceutical form, dosage, and route of administration for this investigational product are not specified in the provided data.

A placebo is utilized as a comparator treatment in this study. The pharmaceutical form and administration details for the placebo are not provided.

The primary efficacy endpoint is the time to first adjudicated clinical disease flare treated by the investigator during the blinded treatment period. Secondary efficacy assessments include the annualized rate of clinical disease flares and the percentage of participants without an adjudicated clinical disease flare who are also off glucocorticoids and immunomodulators. Additional secondary measures include the percentage of participants without an adjudicated clinical disease flare who are off glucocorticoids and the proportion of participants achieving complete remission.

The IgG4-related disease activity will be evaluated using the IgG4-RD RI total activity score. Specific assessments involve the change and percent change in this score from baseline to Week 12 and Week 52, as well as the proportion of participants demonstrating a reduction of $\ge$2 points from the baseline score. The cumulative glucocorticoid dose for the treatment of the condition will also be monitored.