Clinical trial NCT05707377: A Study to Examine the Efficacy and Safety of Zanubrutinib Given to Adults With Primary Membranous Nephropathy
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Primary Membranous Nephropathy
Keywords: BGB-3111
Zanubrutinib
BTKi
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2023-01-31
Enrollment: 282
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Part 1: Change from Baseline in Urine Protein Creatinine Ratio (UPCR)
timeFrame: Baseline and Week 24
measure: Part 2: Number of Participants Achieving Complete Remission
timeFrame: Week 104
Secondary outcomes:
measure: Part 1: Number of participants with Treatment Failure
timeFrame: Week 24
measure: Part 1: Number of Participants with Immunological Response
timeFrame: Week 24
measure: Part 1: Number of Participants with Complete Remission
timeFrame: Week 24, Week 52, Week 76, and Week 104
measure: Part 1: Number of Participants with Overall Remission
timeFrame: Week 24, Week 52, Week 76, and Week 104
measure: Part 1: Number of Participants with Relapse
timeFrame: Week 104
measure: Part 1: Number Of Participants with Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From the first dose of study drug and up to 30 days after study drug discontinuation; up to approximately 68 weeks
measure: Part 2: Number of Participants with Overall Remission
timeFrame: Week 24, Week 52, Week 76, and Week 104
measure: Part 2: Number of Participants with Complete Remission
timeFrame: Week 24, Week 52, and Week 76
measure: Part 2: Number of participants with Treatment Failure
timeFrame: Week 24, Week 52, Week 76, and Week 104
measure: Part 2: Time to First Complete Remission
timeFrame: Up to approximately 104 weeks
measure: Part 2: Time to First Overall Remission
timeFrame: Up to approximately 104 weeks
measure: Part 2: Number of Participants with Relapse
timeFrame: Week 104
measure: Part 2: Time to First Relapse
timeFrame: Up to approximately 104 weeks
measure: Part 2: Health Related quality of Life (HRQoL) Using the Kidney Disease and Quality of Life instrument™ - 36 items (KDQoL-36)
timeFrame: Up to approximately 104 weeks
measure: Part 2: Health Related quality of Life (HRQoL) Using European Quality of Life 5-Dimensions 5-Levels Health Questionnaire (EQ-5D-5L)
timeFrame: Up to approximately 104 weeks
measure: Number of Participants with ≥ 30% Estimated Glomerular Filtration Rate (eGFR) Reduction from Baseline
timeFrame: Baseline, Week 52, and Week 104
measure: Part 2: Number of Participants with TEAEs
timeFrame: From the first dose of study drug and up to 30 days after study drug discontinuation; up to approximately 68 weeks
Other outcomes:
Locations:
city: Northridge
country: United States
facility: Amicis Research Center
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Evanston
country: United States
facility: Northshore University Healthsystem
state: Illinois
city: Minneapolis
country: United States
facility: Intermed Consultants
state: Minnesota
city: Las Vegas
country: United States
facility: Kidney Specialist of Southern Nevada (Ksosn)
state: Nevada
city: Cincinnati
country: United States
facility: University of Cincinnati College of Medicine
state: Ohio
city: Spartanburg
country: United States
facility: Carolina Nephrology
state: South Carolina
city: Houston
country: United States
facility: Prolato Clinical Research Center
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Investigacion Clinica Aplicada
city: Mar del Plata
country: Argentina
facility: Centro de Investigaciones Madicas Mar Del Plata
city: Curitiba
country: Brazil
facility: Instituto Pro Renal Brasil
city: Rio de Janeiro
country: Brazil
facility: Ruschel Medicina E Pesquisa Clinica
city: Sao Paulo
country: Brazil
facility: Hospital Do Rim Fundacao Oswaldo Ramos
city: Sao Paulo
country: Brazil
facility: Hcfmusp Hospital Das Clinicas Da Faculdade de Medicina Da Universidade de Sao Paulo
city: Montreal
country: Canada
facility: Chum (Centre Hospitalier de Luniversite de Montreal) Centre de Recherche
city: Scarborough
country: Canada
facility: Ott Healthcare, Inc (Corporate Medical Centre)
city: Vancouver
country: Canada
facility: University of British Columbia (Providence Health Care Research St Pauls Hospital)
city: Fuyang
country: China
facility: Fuyang Peoples Hospital
state: Anhui
city: Beijing
country: China
facility: Beijing An Zhen Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Peoples Hospital
state: Beijing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Fuzhou
country: China
facility: The First Affiliated Hospital of Fujian Medical University
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Guangzhou
country: China
facility: Guangdong Provincial Peoples Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat Sen University
state: Guangdong
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
state: Guangdong
city: Liuzhou
country: China
facility: Liuzhou Peoples Hospital
state: Guangxi
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Guiyang
country: China
facility: Guizhou Provincial Peoples Hospital
state: Guizhou
city: Shijiazhuang
country: China
facility: The First Hospital of Hebei Medical University
state: Hebei
city: Harbin
country: China
facility: The Second Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of Science and Technology
state: Henan
city: Nanyang
country: China
facility: Nanyang Central Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
state: Hunan
city: Baotou
country: China
facility: The First Affiliated Hospital of Baotou Medical College
state: Inner Mongolia
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Wuxi
country: China
facility: Wuxi Peoples Hospital
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University Branch Xianghu
state: Jiangxi
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
state: Ningxia
city: Jinan
country: China
facility: Shandong Provincial Hospital
state: Shandong
city: Jining
country: China
facility: Affiliated Hospital of Jining Medical University
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University Branch South
state: Shandong
city: Weifang
country: China
facility: Weifang Peoples Hospital
state: Shandong
city: Shanghai
country: China
facility: Rui Jin Hospital Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Shanghai General Hospital
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Provincial Peoples Hospital
state: Shanxi
city: Chengdu
country: China
facility: Sichuan Academy of Medical Sciences and Sichuan Provincial Peoples Hospital
state: Sichuan
city: Zigong
country: China
facility: Zigong First Peoples Hospital, Zigong Academy of Medical Sciences
state: Sichuan
city: Urumqi
country: China
facility: The First Affiliated Hospital of Xinjiang Medical University
state: Xinjiang
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Provincial Peoples Hospital
state: Zhejiang
city: Ningbo
country: China
facility: The First Affiliated Hospital of Ningbo University
state: Zhejiang
city: Olomouc
country: Czechia
facility: Fakultni Nemocnice Olomouc
city: Praha
country: Czechia
facility: Vseobecna Fakultni Nemocnice V Praze
city: Bologna
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Santorsola Malpighi
city: Pavia
country: Italy
facility: Istscientifico Di Pavia, Fondazione Smaugeri, Irccs, Clinica Del Lavoro E Della Riabilitazione
city: Lodz
country: Poland
facility: Spzoz Centralny Szpital Kliniczny Um W Lodzi
city: Olsztyn
country: Poland
facility: Wojewodzki Specjalistyczny Szpital W Olsztynie
city: Erciyes
country: Turkey
facility: Erciyes University Medical Faculty
city: Kocaeli
country: Turkey
facility: Kocaeli University Research and Application Hospital Department of Nephrology
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
city: Carlshalton
country: United Kingdom
facility: St Heliers Hospital
city: Derby
country: United Kingdom
facility: Royal Derby Hospital
city: Liverpool
country: United Kingdom
facility: Aintree University Hospital
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: