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Abstract: INFO16-TH

A Phase 2/3, Multicenter, Randomized, Active-Controlled, Open-Label Study to Evaluate the Efficacy and Safety of Zanubrutinib in Patients with Primary Membranous Nephropathy

Session Information

  • Informational Posters - I
    November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

  • No subcategory defined

Authors

  • Lafayette, Richard A., Stanford University Medical Center, Stanford, California, United States
  • Barbour, Sean, University of British Columbia, Vancouver, British Columbia, Canada
  • Chen, Yanyan, BeiGene Ltd, Beijing, China
  • Zhang, Shenye, BeiGene Ltd, Beijing, China
  • Tankersley, Chris B., BeiGene Ltd, Beijing, China
  • Song, Jingwen, BeiGene Ltd, Beijing, China
  • Yao, Zhen, BeiGene Ltd, Beijing, China
  • Li, Guisen, Sichuan Provincial People’s Hospital, Chengdu, Sichuan, Qingyang District, China
  • Zhao, Ming-Hui, Peking University First Hospital, Beijing, China
Description

Background: Primary membranous nephropathy (pMN) occurs when B cells produce pathogenic autoantibodies against M-PLA2R on podocytes. There are no approved therapies for pMN. Bruton tyrosine kinase (BTK) plays a pivotal role in B-cell receptor signaling; inhibition of BTK may be a promising therapeutic target for pMN. Zanubrutinib is a next-generation BTK inhibitor aimed to maximize BTK occupancy and minimize off-target effects. Here we introduce a study to evaluate the safety and efficacy of zanubrutinib in patients (pts) with pMN.

Methods: ALMOND (BGB-3111-309; NCT05707377) is a 2-part, phase 2/3, multicenter study investigating zanubrutinib in adults aged 18-75 y with biopsy-confirmed pMN. Eligible pts must have a urine protein:creatinine ratio (UPCR) >3.5 (based on 24-h collection) and treatment with a maximally tolerated dose of an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker for ≥24 wk (12 wk in part 1) with adequate blood pressure control before the assignment of study treatment, and anti-PLA2R antibodies >50 RU/mL at screening confirmation assessment (part 1 only).

Part 1 (open-label, single-arm design) will evaluate the efficacy and safety of zanubrutinib 160 mg BID for 64 wk in 30 pts. Part 2 (randomized, open-label, 3-arm withactive-control design) will evaluate zanubrutinib 160 mg BID, zanubrutinib 160 mg QD, or tacrolimus 0.05 mg/kg/d for 64 wk in 252 pts (n=84 in each arm). The primary outcomes are reduction in UPCR (part 1) and the number of pts achieving complete remission (part 2). Secondary outcomes include safety and pts with treatment failure, immunological response, complete or partial remission, and relapse. Secondary outcomes specific to part 2 include time to first complete remission or partial remission, time to first relapse, pts with ≥30% eGFR reduction, and health-related quality of life assessments.

Conclusion: Study enrollment is ongoing.

Funding

  • This study was sponsored by BeiGene, Ltd. Medical writing support, under the direction of the authors, was provided by Medical Expressions, an Inizio company, and was funded by BeiGene, Ltd.