A Study to Examine the Efficacy and Safety of Zanubrutinib Given to Adults With Primary Membranous Nephropathy (ALMOND)

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 (PMN) who are on optimal supportive care.

Study Overview

• Status: Active, not recruiting
• Conditions: Primary Membranous Nephropathy
• Intervention / Treatment: Drug: Zanubrutinib; Drug: Tacrolimus

Detailed Description

Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.

• Study Type: Interventional
• Enrollment (Actual): 178
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Curitiba, Brazil, 80420-011
    • Instituto Pro Renal Brasil
  • São Paulo, Brazil, 05403-000
    • Hcfmusp Hospital Das Clinicas Da Faculdade de Medicina Da Universidade de Sao Paulo
• Canada
  • Ontario
    • Scarborough Village, Ontario, Canada, M1H 3G4
      • Ott Healthcare, Inc (Corporate Medical Centre)
• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100034
      • Peking University First Hospital
    • Beijing, Beijing Municipality, China, 100029
      • Beijing An Zhen Hospital, Capital Medical University
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Fujian Medical University Union Hospital
    • Fuzhou, Fujian, China, 350005
      • The First Affiliated Hospital of Fujian Medical University
    • Xiamen, Fujian, China, 361003
      • The First Affiliated Hospital of Xiamen University
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong Provincial Peoples Hospital
    • Guangzhou, Guangdong, China, 510080
      • The First Affiliated Hospital, Sun Yat Sen University
    • Shenzhen, Guangdong, China, 518036
      • Peking University Shenzhen Hospital
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • The First Affiliated Hospital of Guangxi Medical University
  • Guizhou
    • Guiyang, Guizhou, China, 550002
      • Guizhou Provincial Peoples Hospital
  • Hebei
    • Shijiazhuang, Hebei, China, 50000
      • The First Hospital of Hebei Medical University
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150001
      • The Second Affiliated Hospital of Harbin Medical University
  • Henan
    • Nanyang, Henan, China, 473000
      • Nanyang Central Hospital
    • Zhengzhou, Henan, China, 450052
      • the First Affiliated Hospital of Zhengzhou University
  • Hubei
    • Wuhan, Hubei, China, 430060
      • Renmin Hospital of Wuhan University
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
  • Inner Mongolia
    • Baotou, Inner Mongolia, China, 14017
      • The First Affiliated Hospital of Baotou Medical College
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Jiangsu Province Hospital
    • Wuxi, Jiangsu, China, 214023
      • Wuxi Peoples Hospital
  • Ningxia
    • Yinchuan, Ningxia, China, 750004
      • General Hospital of Ningxia Medical University
  • Shandong
    • Jinan, Shandong, China, 250021
      • Shandong Provincial Hospital
    • Qingdao, Shandong, China, 266000
      • The Affiliated Hospital of Qingdao University Branch South
    • Weifang, Shandong, China, 261000
      • Weifang Peoples Hospital
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200080
      • Shanghai General Hospital
    • Shanghai, Shanghai Municipality, China, 200025
      • Rui Jin Hospital Shanghai Jiao Tong University School of Medicine
  • Shanxi
    • Taiyuan, Shanxi, China, 030012
      • Shanxi Provincial Peoples Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610071
      • Sichuan Academy of Medical Sciences and Sichuan Provincial Peoples Hospital
  • Xinjiang
    • Ürümqi, Xinjiang, China, 830054
      • The First Affiliated Hospital of Xinjiang Medical University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital, Zhejiang University School of Medicine
    • Hangzhou, Zhejiang, China, 310014
      • Zhejiang Provincial Peoples Hospital
    • Ningbo, Zhejiang, China, 315010
      • The First Affiliated Hospital of Ningbo University
• Czechia
  • Olomouc, Czechia, 77900
    • Fakultni Nemocnice Olomouc
  • Prague, Czechia, 10000
    • Vseobecna Fakultni Nemocnice V Praze
• Italy
  • Pavia, Italy, 27100
    • Istscientifico Di Pavia, Fondazione Smaugeri, Irccs, Clinica Del Lavoro E Della Riabilitazione
• Russia
  • Chechenskaya Respublika
    • Grozny, Chechenskaya Respublika, Russia, 364029
      • Medical Company Llc
• Turkey (Türkiye)
  • Erciyes, Turkey (Türkiye), 38030
    • Erciyes University Medical Faculty
  • Kocaeli, Turkey (Türkiye), 41380
    • Kocaeli University Research and Application Hospital Department of Nephrology
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
    • Aberdeen Royal Infirmary
  • Derby, United Kingdom, DE22 3NE
    • Royal Derby Hospital
• United States
  • California
    • Granada Hills, California, United States, 91344
      • Amicis Research Center
    • Palo Alto, California, United States, 94304
      • Stanford University
  • Minnesota
    • Minneapolis, Minnesota, United States, 55435-2130
      • Intermed Consultants
  • Nevada
    • Las Vegas, Nevada, United States, 89106-4852
      • Kidney Specialist of Southern Nevada (Ksosn)
  • Ohio
    • Cincinnati, Ohio, United States, 45267-2827
      • University of Cincinnati College of Medicine
  • South Carolina
    • Spartanburg, South Carolina, United States, 29306-3927
      • Carolina Nephrology

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 PMN 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 at 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 (blood pressure < 130/80 mmHg, measured on ≥ 2 occasions [not on the same day] within 4 weeks before the assignment of study treatment)
• 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
• Severe renal disease as determined by rapid decline in eGFR (defined as > 15 mL/min/1.73m^2 within 24 weeks prior to randomization, not otherwise explained)
• 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: Other protocol defined Inclusion/Exclusion 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

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Change from Baseline in Urine Protein Creatinine Ratio (UPCR)		Baseline and Week 24
Part 2: Number of Participants Achieving Complete Remission	Complete remission is defined as: UPCR (based on 24-hour urine collection) ≤ 0.3, AND a stable estimated glomerular filtration rate (eGFR) (remains unchanged or decreases by < 15% compared with the baseline)	Week 104

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 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 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 Treatment Failure		Week 24, Week 52, Week 76, and Week 104
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 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 relative units (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 Treatment-Emergent Adverse Events (TEAEs)		From the first dose of study drug and up to 30 days after study drug discontinuation; up to approximately 68 weeks
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: 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 104 weeks
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 104 weeks
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 104 weeks
Part 2: Health Related quality of Life (HRQoL) Using the Kidney Disease and Quality of Life instrument™ - 36 items (KDQoL-36)		Up to approximately 104 weeks
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 104 weeks
Number of Participants with ≥ 30% Estimated Glomerular Filtration Rate (eGFR) Reduction from Baseline		Baseline, Week 52, and Week 104
Part 2: Number of Participants with TEAEs		From the first dose of study drug and up to 30 days after study drug discontinuation; up to approximately 68 weeks

Collaborators and Investigators

• Sponsor: BeOne Medicines
• Investigators: Study Director: Study Director, BeOne Medicines

Publications and helpful links

General Publications

• Ahmad SB, Jefferson JA. Targeting B Cells and Plasma Cells in Glomerular Disease. J Am Soc Nephrol. 2025 Jun 4;36(9):1844-1857. doi: 10.1681/ASN.0000000772.

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2023
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027

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 3, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: BTKi; Zanubrutinib; BGB-3111
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Kidney Diseases; Glomerulonephritis, Membranous; Organic Chemicals; Macrolides; Lactones; Tacrolimus; zanubrutinib
• Other Study ID Numbers: BGB-3111-309; 2022-501147-32-00 (Registry Identifier: EU CTIS); CTR20230546 (Registry Identifier: ChinaDrugTrials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

BeOne shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved.

BeOne shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations.

Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeOne review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

• IPD Sharing Time Frame: See plan description
• IPD Sharing Access Criteria: See plan description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

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