POS0347 INSIGHTS INTO THE DESIGN AND STUDY POPULATION OF MITIGATE: THE FIRST MULTINATIONAL RANDOMIZED CONTROLLED CLINICAL TRIAL IN IgG4 RELATED DISEASE (IgG4-RD), EVALUATING THE EFFICACY AND SAFETY OF INEBILIZUMAB

Background: IgG4-RD has substantial unmet medical needs, with no approved medications and lack of controlled clinical trial data to inform treatment decisions. The roles of B cells in IgG4-RD pathophysiology and existing clinical experience suggest B cell depletion may be an effective therapeutic avenue. Inebilizumab is a humanized, glycoengineered CD19-directed monoclonal antibody that effectively and selectively depletes B cells. The Phase 3 MITIGATE trial (NCT04540497) is a randomized, double-blind, placebo-controlled trial being conducted at 80 sites in 22 countries. Objectives: MITIGATE aims to demonstrate the efficacy and safety of inebilizumab in reducing the risk of IgG4-RD flares. Methods: The study enrolled 135 adults with IgG4-RD who met the ACR/EULAR IgG4-RD Classification Criteria with a score of at least 20 as determined by an Eligibility Committee (EC). Eligibility criteria included multiorgan disease history and active disease being treated with glucocorticoids at the time of screening to increase the risk of flares for the primary endpoint. The most common reasons for screen failure were HIV/hepatitis B, tuberculosis, requirements for glucocorticoid treatment of recent flare, exclusionary blood labs, and failure to meet the ACR/EULAR classification criteria. Subjects were stratified based on newly diagnosed (46%) vs. recurrent (54%) disease to control for potential differences in flare risk. The primary endpoint is time to first Adjudication Committee-determined and investigator-treated IgG4-RD flare during the 12-month randomized controlled period (RCP). Inebilizumab is being evaluated as monotherapy, as other immunosuppressive agents are prohibited and glucocorticoids are discontinued at the end of study week 8. Results: The mean participant age was 58.2 years and 65% of patients were male. Time since diagnosis ranged from 0.1 - 20.5 years (median 0.9). Baseline ACR/EULAR Classification Criteria scores as determined by the EC ranged from 20 to 74. The number of organs affected by IgG4-RD up to the time of enrollment varied from 2 to 13, with 2-3 organs affected in 41% of subjects and ≥ 6 organs affected in 24% (Figure 1). The organs affected in ≥ 25% of the study population include the pancreas, lymph nodes, submandibular and lacrimal glands, hepatobiliary system, kidneys, and lungs (Table 1). More than half (52%) of patients had pancreatic IgG4-RD involvement, and 45% and 33% had submandibular gland disease and renal disease respectively. These data indicate that the study population is representative of real-world IgG4-RD cohorts. Enrollment was completed in April 2023. The Adjudication Committee has evaluated approximately 80 potential disease flares in the RCP to date, and the study target of 39 events for the primary endpoint has been exceeded. Topline results are anticipated in 2024. Conclusion: MITIGATE has completed its global enrollment with multiorgan involvement representative of an IgG4-RD population, both in terms of number and distribution of organs affected. This study aims to establish the safety and efficacy of CD19-targeted B cell depletion by inebilizumab in IgG4-RD, potentially leading to the first approved treatment for this disease. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: John H. Stone Amgen, Inc., Emma L. Culver Amgen, Inc, Arezou Khosroshahi Amgen, Inc., Wen Zhang Amgen, Inc., Emanuel Della Torre Amgen, Inc., Kazuichi Okazaki Amgen, Inc., Yoshiya Tanaka Amgen, Inc., Matthias Lohr Amgen, Inc., Nicolas Schleinitz Amgen, Inc., Lingli Dong Amgen, Inc., Hisanori Umehara Amgen, Inc., Marco Lanzillotta Amgen, Inc., Zachary S. Wallace Amgen, Inc., Mikael Ebbo Amgen, Inc., George Webster Amgen, Inc., Yanping Wu Amgen, Inc., Amgen, Inc., Daniel Cimbora Amgen, Amgen, Nishi Rampal Amgen, Inc., Amgen, Inc.