A Study to Evaluate the Safety and Efficacy of Zanubrutinib in Participants With Primary Membranous Nephropathy

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

The primary objectives of this study are: In Part 1 to evaluate the efficacy of zanubrutinib as measured by proteinuria reduction, and in Part 2 to evaluate the efficacy of zanubrutinib compared with tacrolimus as measured by complete remission rate, in participants with primary membranous nephropathy who are on optimal supportive care.

Study Overview

• Status: Recruiting
• Conditions: Primary Membranous Nephropathy
• Intervention / Treatment: Drug: Zanubrutinib; Drug: Tacrolimus; Drug: Zanubrutinib

• Study Type: Interventional
• Enrollment (Estimated): 282
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Study Director; Phone Number: 1-877-828-5568; Email: clinicaltrials@beigene.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100034
      • Recruiting
      • Peking University First Hospital
    • Beijing, Beijing, China, 100044
      • Recruiting
      • Peking University Peoples Hospital
    • Beijing, Beijing, China, 100029
      • Recruiting
      • Beijing An Zhen Hospital of the Capital University of Medical Sciences
  • Fujian
    • Fuzhou, Fujian, China, 350005
      • Recruiting
      • The First Affiliated Hospital of Fujian Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Recruiting
      • Guangdong Provincial Peoples Hospital
    • Guangzhou, Guangdong, China, 510080
      • Recruiting
      • The First Affiliated Hospital, Sun Yat Sen University
    • Shenzhen, Guangdong, China, 518036
      • Recruiting
      • Peking University Shenzhen Hospital
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • Recruiting
      • The First Affiliated Hospital of Guangxi Medical University
  • Guizhou
    • Guiyang, Guizhou, China, 550002
      • Recruiting
      • Guizhou Provincial Peoples Hospital
  • Hebei
    • Shijiazhuang, Hebei, China, 50000
      • Recruiting
      • The First Hospital of Hebei Medical University
  • Henan
    • Nanyang, Henan, China, 473000
      • Recruiting
      • Nanyang Central Hospital
    • Zhengzhou, Henan, China, 450052
      • Recruiting
      • The First Affiliated Hospital of Zhengzhou University
  • Hubei
    • Wuhan, Hubei, China, 430060
      • Recruiting
      • Renmin Hospital of Wuhan University
  • Inner Mongolia
    • Baotou, Inner Mongolia, China, 14017
      • Recruiting
      • The First Affiliated Hospital of Baotou Medical College
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Recruiting
      • Zhongda Hospital Southeast University
    • Nanjing, Jiangsu, China, 210029
      • Recruiting
      • Jiangsu Province Hospital
    • Wuxi, Jiangsu, China, 214023
      • Recruiting
      • Wuxi Peoples Hospital
    • Zhenjiang, Jiangsu, China, 212001
      • Recruiting
      • Affiliated Hospital of Jiangsu University
  • Liaoning
    • Dalian, Liaoning, China, 116011
      • Recruiting
      • First Affiliated Hospital of Dalian Medical University
    • Shenyang, Liaoning, China, 110004
      • Recruiting
      • Shengjing Hospital of China Medical University
  • Ningxia
    • Yinchuan, Ningxia, China, 750004
      • Recruiting
      • General Hospital of Ningxia Medical University
  • Shandong
    • Jinan, Shandong, China, 250021
      • Recruiting
      • Shandong Provincial Hospital
    • Qingdao, Shandong, China, 266000
      • Recruiting
      • The Affiliated Hospital of Qingdao University Branch South
  • Shanghai
    • Shanghai, Shanghai, China, 200080
      • Recruiting
      • Shanghai General Hospital
    • Shanghai, Shanghai, China, 200025
      • Recruiting
      • Rui Jin Hospital Shanghai Jiao Tong University School of Medicine
  • Shanxi
    • Taiyuan, Shanxi, China, 030012
      • Recruiting
      • Shanxi Provincial Peoples Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610071
      • Recruiting
      • Sichuan Academy of Medical Sciences and Sichuan Provincial Peoples Hospital
  • Xinjiang
    • Urumqi, Xinjiang, China, 830054
      • Recruiting
      • The First Affiliated Hospital of Xinjiang Medical University
  • Yunnan
    • Kunming, Yunnan, China, 650034
      • Recruiting
      • The First Peoples Hospital of Yunnan Province
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The First Affiliated Hospital, Zhejiang University School of Medicine
    • Hangzhou, Zhejiang, China, 310014
      • Recruiting
      • Zhejiang Provincial Peoples Hospital
    • Ningbo, Zhejiang, China, 315010
      • Recruiting
      • Ningbo First Hospital
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
    • Recruiting
    • Aberdeen Royal Infirmary
  • Carlshalton, United Kingdom, SM5 1AA
    • Recruiting
    • St Heliers Hospital
  • Derby, United Kingdom, DE22 3NE
    • Recruiting
    • Royal Derby Hospital
  • Liverpool, United Kingdom, L9 7AL
    • Recruiting
    • Aintree University Hospital
  • London, United Kingdom, W12 0HS
    • Recruiting
    • Hammersmith Hospital
  • Manchester, United Kingdom, M13 9WL
    • Recruiting
    • Manchester Royal Infirmary
• United States
  • California
    • Northridge, California, United States, 91324
      • Recruiting
      • Amicis Research Center
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Stanford University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University Feinberg School of Medicine
    • Evanston, Illinois, United States, 60201
      • Recruiting
      • NorthShore University HealthSystem
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Recruiting
      • InterMed Consultants
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Recruiting
      • Kidney Specialist of Southern Nevada (Ksosn)
  • South Carolina
    • Spartanburg, South Carolina, United States, 29306
      • Recruiting
      • Carolina Nephrology
  • Texas
    • Houston, Texas, United States, 77054
      • Recruiting
      • Prolato Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Biopsy-confirmed primary membranous nephropathy within 5 years before the initial screening (ie, the day the informed consent is signed)
• UPCR (based on 24-hour urine collection) > 3.5 at initial screening and confirmation assessment
• Treatment with a maximally tolerated or allowed dose of an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) for ≥ 24 weeks before randomization (12 weeks before initiation of study drug for Part 1) and with adequate blood pressure control
• Anti-PLA2R antibody > 50 RU/mL at confirmation assessment (Part 1 only)

Exclusion Criteria:

• Participants with a secondary cause of membranous nephropathy
• Type 1 or 2 diabetes mellitus with hemoglobin A1c (HbA1c) ≥ 7% at screening
• A known history of a primary immunodeficiency or an underlying condition such as human immunodeficiency virus (HIV) infection or splenectomy that predisposes the participant to infections
• Patients at risk for tuberculosis at screening
• Known infection with serologic status reflecting active or chronic hepatitis B virus infection, or presence of hepatitis C virus antibody
• Severe hepatic insufficiency (Child-Pugh C)
• Clinically significant cardio-cerebrovascular diseases

Note: Additional criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 and Part 2: Zanubrutinib High dose; Participants will receive Zanubrutinib twice daily	Drug: Zanubrutinib; Participants will receive zanubrutinib once daily; Other Names: BGB-3111; Drug: Zanubrutinib; Participants will receive zanubrutinib twice daily; Other Names: BGB-3111
Experimental: Part 2: Zanubrutinib Low Dose; Participants will receive Zanubrutinib once daily	Drug: Zanubrutinib; Participants will receive zanubrutinib once daily; Other Names: BGB-3111; Drug: Zanubrutinib; Participants will receive zanubrutinib twice daily; Other Names: BGB-3111
Active Comparator: Tacrolimus; Participants will receive tacrolimus capsules for 64 weeks	Drug: Tacrolimus; Participants will receive tacrolimus twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part 2: Number of Participants Achieving Complete Remission	Week 104
Part 1: Change from Baseline in Urine Protein Creatinine Ratio (UPCR)	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Number of participants with Treatment Failure		Week 24
Part 1: Number of Participants with Immunological Response	Immunological response is defined as anti- phospholipase A2 receptor (PLA2R) antibody level reduced from baseline to less than 14 RU/ml.	Week 24
Part 1: Number of Participants with Complete Remission	A complete remission is defined as: UPCR (based on 24-hour urine collection) ≤ 0.3, AND A stable eGFR (remains unchanged or decreases by < 15% compared with the baseline)	Week 24, Week 52, Week 76, and Week 104
Part 1: Number of Participants with Overall Remission	Participants with overall remission are those achieving either complete remission or partial remission	Week 24, Week 52, Week 76, and Week 104
Part 1: Number of Participants with Relapse	A relapse is defined as reappearance of UPCR (based on 24-hour urine collection) > 3.5 after complete or partial remission	Week 104
Part 1: Number Of Participants with Treatment-Emergent Adverse Events (TEAEs)		Up to approximately 104 weeks
Part 2: Number of Participants with Overall Remission	Participants with overall remission are those achieving either complete remission or partial remission	Week 24, Week 52, Week 76, and Week 104
Part 2: Number of Participants with Complete Remission	A complete remission is defined as: UPCR (based on 24-hour urine collection) ≤ 0.3, and A stable eGFR (remains unchanged or decreases by < 15% compared with the baseline)	Week 24, Week 52, and Week 76
Part 2: Number of participants with Treatment Failure		Week 24, Week 52, Week 76, and Week 104
Part 2: Time to First Complete Remission	Time to First Complete Remission is the time from the date of randomization to the date of the first complete remission	Up to approximately 5.5 years
Part 2: Time to First Overall Remission	Time to first overall remission is the time from the date of randomization to the date of the first overall remission	Up to approximately 5.5 years
Part 2: Number of Participants with Relapse	A relapse is defined as reappearance of UPCR (based on 24-hour urine collection) > 3.5 after complete or partial remission	Week 104
Part 2: Time to First Relapse	Time to first relapse is the time from the date of first complete or partial remission to the date of the first relapse	Up to approximately 5.5 years
Part 2: Health Related quality of Life (HRQoL) Using European Quality of Life 5-Dimensions 5-Levels Health Questionnaire (EQ-5D-5L)		Up to approximately 5.5 years
Part 2: Number of Participants with TEAEs		Up to approximately 5.5 years
Part 2: Health Related quality of Life (HRQoL) Using the Kidney Disease and Quality of Life instrument™ - 36 items (KDQoL-36)		Up to approximately 5.5 years
Number of Participants with ≥ 30% Estimated Glomerular Filtration Rate (eGFR) Reduction from Baseline		Week 52 and Week 104

Collaborators and Investigators

• Sponsor: BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2023
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: January 23, 2023
• First Submitted That Met QC Criteria: January 23, 2023
• First Posted (Actual): January 31, 2023

Study Record Updates

• Last Update Posted (Actual): June 6, 2024
• Last Update Submitted That Met QC Criteria: June 5, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Glomerulonephritis, Membranous; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protein Kinase Inhibitors; Calcineurin Inhibitors; Tyrosine Kinase Inhibitors; Tacrolimus; Zanubrutinib
• Other Study ID Numbers: BGB-3111-309; 2022-501147-32-00 (Registry Identifier: EU CTIS); CTR20230546 (Registry Identifier: ChinaDrugTrials)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No