A Study to Examine the Efficacy and Safety of Zanubrutinib Given to Adults With Primary Membranous Nephropathy
- Conditions
- Primary Membranous Nephropathy
- Interventions
- Registration Number
- NCT05707377
- Lead Sponsor
- BeiGene
- Brief 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 optimal supportive care.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 282
- 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)
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1: Zanubrutinib High Dose Zanubrutinib Participants will receive zanubrutinib twice daily. Part 2: Zanubrutinib High Dose Zanubrutinib Participants will receive zanubrutinib twice daily. Part 2: Tacrolimus Tacrolimus Participants will receive tacrolimus capsules twice daily for 64 weeks. Part 2: Zanubrutinib Low Dose Zanubrutinib Participants will receive zanubrutinib once daily.
- Primary Outcome Measures
Name Time Method Part 1: Change from Baseline in Urine Protein Creatinine Ratio (UPCR) Baseline and Week 24 Part 2: Number of Participants Achieving Complete Remission Week 104 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)
- Secondary Outcome Measures
Name Time Method Part 1: Number of participants with Treatment Failure Week 24 Part 1: Number of Participants with Immunological Response Week 24 Immunological response is defined as anti- phospholipase A2 receptor (PLA2R) antibody level reduced from baseline to less than 14 relative units (RU)/ml.
Part 1: Number of Participants with Complete Remission Week 24, Week 52, Week 76, and Week 104 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)Part 1: Number of Participants with Overall Remission Week 24, Week 52, Week 76, and Week 104 Participants with overall remission are those achieving either complete remission or partial remission
Part 1: Number of Participants with Relapse Week 104 A relapse is defined as reappearance of UPCR (based on 24-hour urine collection) \> 3.5 after complete or partial remission
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 Overall Remission Week 24, Week 52, Week 76, and Week 104 Participants with overall remission are those achieving either complete remission or partial remission
Part 2: Number of Participants with Complete Remission Week 24, Week 52, and Week 76 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)Part 2: Number of participants with Treatment Failure Week 24, Week 52, Week 76, and Week 104 Part 2: Time to First Complete Remission Up to approximately 104 weeks Time to First Complete Remission is the time from the date of randomization to the date of the first complete remission
Part 2: Time to First Overall Remission Up to approximately 104 weeks Time to first overall remission is the time from the date of randomization to the date of the first overall remission
Part 2: Number of Participants with Relapse Week 104 A relapse is defined as reappearance of UPCR (based on 24-hour urine collection) \> 3.5 after complete or partial remission
Part 2: Time to First Relapse Up to approximately 104 weeks Time to first relapse is the time from the date of first complete or partial remission to the date of the first relapse
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
Trial Locations
- Locations (71)
Erciyes University Medical Faculty
🇹🇷Erciyes, Turkey
Ruschel Medicina E Pesquisa Clinica
🇧🇷Rio de Janeiro, Brazil
Investigacion Clinica Aplicada
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Hospital Do Rim Fundacao Oswaldo Ramos
🇧🇷Sao Paulo, Brazil
Amicis Research Center
🇺🇸Northridge, California, United States
Stanford University
🇺🇸Palo Alto, California, United States
Northwestern University Feinberg School of Medicine
🇺🇸Chicago, Illinois, United States
Northshore University Healthsystem
🇺🇸Evanston, Illinois, United States
Intermed Consultants
🇺🇸Minneapolis, Minnesota, United States
Kidney Specialist of Southern Nevada (Ksosn)
🇺🇸Las Vegas, Nevada, United States
University of Cincinnati College of Medicine
🇺🇸Cincinnati, Ohio, United States
Carolina Nephrology
🇺🇸Spartanburg, South Carolina, United States
Prolato Clinical Research Center
🇺🇸Houston, Texas, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Centro de Investigaciones Madicas Mar Del Plata
🇦🇷Mar del Plata, Argentina
Instituto Pro Renal Brasil
🇧🇷Curitiba, Brazil
Hcfmusp Hospital Das Clinicas Da Faculdade de Medicina Da Universidade de Sao Paulo
🇧🇷Sao Paulo, Brazil
Chum (Centre Hospitalier de Luniversite de Montreal) Centre de Recherche
🇨🇦Montreal, Canada
Ott Healthcare, Inc (Corporate Medical Centre)
🇨🇦Scarborough, Canada
University of British Columbia (Providence Health Care Research St Pauls Hospital)
🇨🇦Vancouver, Canada
Fuyang Peoples Hospital
🇨🇳Fuyang, Anhui, China
Beijing An Zhen Hospital, Capital Medical University
🇨🇳Beijing, Beijing, China
Peking University First Hospital
🇨🇳Beijing, Beijing, China
Peking University Peoples Hospital
🇨🇳Beijing, Beijing, China
Fujian Medical University Union Hospital
🇨🇳Fuzhou, Fujian, China
The First Affiliated Hospital of Fujian Medical University
🇨🇳Fuzhou, Fujian, China
The First Affiliated Hospital of Xiamen University
🇨🇳Xiamen, Fujian, China
Guangdong Provincial Peoples Hospital
🇨🇳Guangzhou, Guangdong, China
The First Affiliated Hospital, Sun Yat Sen University
🇨🇳Guangzhou, Guangdong, China
Peking University Shenzhen Hospital
🇨🇳Shenzhen, Guangdong, China
Liuzhou Peoples Hospital
🇨🇳Liuzhou, Guangxi, China
The First Affiliated Hospital of Guangxi Medical University
🇨🇳Nanning, Guangxi, China
Guizhou Provincial Peoples Hospital
🇨🇳Guiyang, Guizhou, China
The First Hospital of Hebei Medical University
🇨🇳Shijiazhuang, Hebei, China
The Second Affiliated Hospital of Harbin Medical University
🇨🇳Harbin, Heilongjiang, China
The First Affiliated Hospital of Henan University of Science and Technology
🇨🇳Luoyang, Henan, China
Nanyang Central Hospital
🇨🇳Nanyang, Henan, China
The First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, Henan, China
Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Renmin Hospital of Wuhan University
🇨🇳Wuhan, Hubei, China
Xiangya Hospital of Central South University
🇨🇳Changsha, Hunan, China
The First Affiliated Hospital of Baotou Medical College
🇨🇳Baotou, Inner Mongolia, China
Jiangsu Province Hospital
🇨🇳Nanjing, Jiangsu, China
Wuxi Peoples Hospital
🇨🇳Wuxi, Jiangsu, China
The First Affiliated Hospital of Nanchang University Branch Xianghu
🇨🇳Nanchang, Jiangxi, China
General Hospital of Ningxia Medical University
🇨🇳Yinchuan, Ningxia, China
Shandong Provincial Hospital
🇨🇳Jinan, Shandong, China
Affiliated Hospital of Jining Medical University
🇨🇳Jining, Shandong, China
The Affiliated Hospital of Qingdao University Branch South
🇨🇳Qingdao, Shandong, China
Weifang Peoples Hospital
🇨🇳Weifang, Shandong, China
Rui Jin Hospital Shanghai Jiao Tong University School of Medicine
🇨🇳Shanghai, Shanghai, China
Shanghai General Hospital
🇨🇳Shanghai, Shanghai, China
Shanxi Provincial Peoples Hospital
🇨🇳Taiyuan, Shanxi, China
Sichuan Academy of Medical Sciences and Sichuan Provincial Peoples Hospital
🇨🇳Chengdu, Sichuan, China
Zigong First Peoples Hospital, Zigong Academy of Medical Sciences
🇨🇳Zigong, Sichuan, China
The First Affiliated Hospital of Xinjiang Medical University
🇨🇳Urumqi, Xinjiang, China
The First Affiliated Hospital, Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Zhejiang Provincial Peoples Hospital
🇨🇳Hangzhou, Zhejiang, China
The First Affiliated Hospital of Ningbo University
🇨🇳Ningbo, Zhejiang, China
Fakultni Nemocnice Olomouc
🇨🇿Olomouc, Czechia
Vseobecna Fakultni Nemocnice V Praze
🇨🇿Praha, Czechia
Azienda Ospedaliera Universitaria Policlinico Santorsola Malpighi
🇮🇹Bologna, Italy
Istscientifico Di Pavia, Fondazione Smaugeri, Irccs, Clinica Del Lavoro E Della Riabilitazione
🇮🇹Pavia, Italy
Spzoz Centralny Szpital Kliniczny Um W Lodzi
🇵🇱Lodz, Poland
Wojewodzki Specjalistyczny Szpital W Olsztynie
🇵🇱Olsztyn, Poland
Kocaeli University Research and Application Hospital Department of Nephrology
🇹🇷Kocaeli, Turkey
Aberdeen Royal Infirmary
🇬🇧Aberdeen, United Kingdom
St Heliers Hospital
🇬🇧Carlshalton, United Kingdom
Royal Derby Hospital
🇬🇧Derby, United Kingdom
Aintree University Hospital
🇬🇧Liverpool, United Kingdom
Manchester Royal Infirmary
🇬🇧Manchester, United Kingdom