Primary Membranous NephropathyPhase 2/3ALMONDNCT05707377
A Study to Examine the Efficacy and Safety of Zanubrutinib Given to Adults With Primary Membranous Nephropathy
A Phase 2/3 study testing Zanubrutinib and Tacrolimus in people with Primary Membranous Nephropathy, run by BeOne Medicines at 45 sites in 9 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Primary Membranous Nephropathy
- What is being tested?
- Zanubrutinib and Tacrolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 178 participants
- Where
- 45 sitesin 9 countries
- Study dates
- 17 Apr 2023to Oct 2027
- Phase
- Phase 2/3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
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- Severe hepatic insufficiency (Child-Pugh C)
- Clinically significant cardio-cerebrovascular diseases
- Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
45 sites in 9 countries.
45 sites in 9 countries
China31 sites
The First Affiliated Hospital of Baotou Medical College
Baotou, Inner Mongolia, 14017
Beijing An Zhen Hospital, Capital Medical University
Beijing, Beijing Municipality, 100029
Peking University First Hospital
Beijing, Beijing Municipality, 100034
Sichuan Academy of Medical Sciences and Sichuan Provincial Peoples Hospital
Chengdu, Sichuan, 610071
Fujian Medical University Union Hospital
Fuzhou, Fujian, 350001
The First Affiliated Hospital of Fujian Medical University
Fuzhou, Fujian, 350005
Guangdong Provincial Peoples Hospital
Guangzhou, Guangdong, 510080
The First Affiliated Hospital, Sun Yat Sen University
Guangzhou, Guangdong, 510080
Guizhou Provincial Peoples Hospital
Guiyang, Guizhou, 550002
The First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310003
Zhejiang Provincial Peoples Hospital
Hangzhou, Zhejiang, 310014
The Second Affiliated Hospital of Harbin Medical University
Harbin, Heilongjiang, 150001
Shandong Provincial Hospital
Jinan, Shandong, 250000
Jiangsu Province Hospital
Nanjing, Jiangsu, 210029
The First Affiliated Hospital of Guangxi Medical University
Nanning, Guangxi, 530021
Nanyang Central Hospital
Nanyang, Henan, 473000
The First Affiliated Hospital of Ningbo University
Ningbo, Zhejiang, 315010
The Affiliated Hospital of Qingdao University Branch South
Qingdao, Shandong, 266000
Rui Jin Hospital Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, 200025
Shanghai General Hospital
Shanghai, Shanghai Municipality, 200080
Peking University Shenzhen Hospital
Shenzhen, Guangdong, 518036
The First Hospital of Hebei Medical University
Shijiazhuang, Hebei, 50000
Shanxi Provincial Peoples Hospital
Taiyuan, Shanxi, 030012
The First Affiliated Hospital of Xinjiang Medical University
Ürümqi, Xinjiang, 830054
Weifang Peoples Hospital
Weifang, Shandong, 261000
Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
Wuhan, Hubei, 430030
Renmin Hospital of Wuhan University
Wuhan, Hubei, 430060
Wuxi Peoples Hospital
Wuxi, Jiangsu, 214023
The First Affiliated Hospital of Xiamen University
Xiamen, Fujian, 361003
General Hospital of Ningxia Medical University
Yinchuan, Ningxia, 750004
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, 450052
United States4 sites
Amicis Research Center
Granada Hills, California, 91344
Kidney Specialist of Southern Nevada (Ksosn)
Las Vegas, Nevada, 89106-4852
Intermed Consultants
Minneapolis, Minnesota, 55435-2130
Stanford University
Palo Alto, California, 94304
Czechia2 sites
Fakultni Nemocnice Olomouc
Olomouc, 77900
Vseobecna Fakultni Nemocnice V Praze
Prague, 10000
Turkey (Türkiye)2 sites
Erciyes University Medical Faculty
Erciyes, 38030
Kocaeli University Research and Application Hospital Department of Nephrology
Kocaeli, 41380
United Kingdom2 sites
Aberdeen Royal Infirmary
Aberdeen, AB25 2ZN
Royal Derby Hospital
Derby, DE22 3NE
Canada1 site
Ott Healthcare, Inc (Corporate Medical Centre)
Scarborough Village, Ontario, M1H 3G4
Italy1 site
Istscientifico Di Pavia, Fondazione Smaugeri, Irccs, Clinica Del Lavoro E Della Riabilitazione
Pavia, 27100
About this study
Official title: 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.
Read the 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.
- Conditions
- Primary Membranous Nephropathy
- Being tested
- Zanubrutinib, Tacrolimus
- Keywords
- BGB-3111, Zanubrutinib, BTKi
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZanubrutinibDrug
Also called BGB-3111, Brukinsa
Zanubrutinib capsules administered orally.
TacrolimusDrug
Tacrolimus capsules administered orally.
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Zanubrutinib High Dose | Experimental | Participants will receive zanubrutinib twice daily. Receives: Drug: Zanubrutinib |
| Part 2: Zanubrutinib High Dose | Experimental | Participants will receive zanubrutinib twice daily. Receives: Drug: Zanubrutinib |
| Part 2: Zanubrutinib Low Dose | Experimental | Participants will receive zanubrutinib once daily. Receives: Drug: Zanubrutinib |
| Part 2: Tacrolimus | Active comparator | Participants will receive tacrolimus capsules twice daily for 64 weeks. Receives: Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Change from Baseline in Urine Protein Creatinine Ratio (UPCR)
Measured: 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)
Measured: Week 104
Secondary outcomes (17)
Part 1: Number of participants with Treatment Failure
Measured: 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 relative units (RU)/ml.
Measured: 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)
Measured: 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
Measured: 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
Measured: Week 104
Part 1: Number Of Participants with Treatment-Emergent Adverse Events (TEAEs)
Measured: 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 Overall Remission
Participants with overall remission are those achieving either complete remission or partial remission
Measured: 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)
Measured: Week 24, Week 52, and Week 76
Part 2: Number of participants with Treatment Failure
Measured: 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
Measured: 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
Measured: Up to approximately 104 weeks
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
Measured: 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
Measured: 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)
Measured: 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)
Measured: Up to approximately 104 weeks
Number of Participants with ≥ 30% Estimated Glomerular Filtration Rate (eGFR) Reduction from Baseline
Measured: Baseline, Week 52, and Week 104
Part 2: Number of Participants with TEAEs
Measured: From the first dose of study drug and up to 30 days after study drug discontinuation; up to approximately 68 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2023
- Study start17 Apr 2023
- Primary completionOct 2027 (estimated)
- Study completionOct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Primary Membranous NephropathyStudies of the same condition, open and under way.
- More trials run by BeOne MedicinesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- In Part I, participants will be assigned to one treatment group. After enrollment in Part I is complete, enrollment in Part 2 will start. In Part 2, participants will be randomly assigned to 1 of 3 treatment groups.
- Masking
- None (open label)
- Enrolment
- 178 participants (actual)
Sponsor and investigators
- Lead sponsor
- BeOne Medicines
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, BeOne Medicines
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05707377
- Sponsor's protocol ID
- BGB-3111-309
- Other IDs
- 2022-501147-32-00, CTR20230546
- Acronym
- ALMOND
- Status last verified
- Sep 2026
- First submitted
- 23 Jan 2023
- Last updated
- 11 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
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.
PubMed 40465397