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

Primary Membranous Nephropathy Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05707377
• Other study ID #: BGB-3111-309
• Secondary ID: 2022-501147-32-0
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: April 17, 2023
• Est. completion date: December 2028

Study information

• Verified date: June 2024
• Source: BeiGene
• Contact: Study Director
• Phone: 1-877-828-5568
• Email: clinicaltrials[@]beigene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 who are on optimal supportive care.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 282
• Est. completion date: December 2028
• Est. primary completion date: December 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Glomerulonephritis, Membranous
• Kidney Diseases
• Primary Membranous Nephropathy

Intervention

Drug:
• Zanubrutinib
Participants will receive zanubrutinib once daily
• Tacrolimus
Participants will receive tacrolimus twice daily
• Zanubrutinib
Participants will receive zanubrutinib twice daily

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Baotou Medical College	Baotou	Inner Mongolia
China	Beijing An Zhen Hospital of the Capital University of Medical Sciences	Beijing	Beijing
China	Peking University First Hospital	Beijing	Beijing
China	Peking University Peoples Hospital	Beijing	Beijing
China	Sichuan Academy of Medical Sciences and Sichuan Provincial Peoples Hospital	Chengdu	Sichuan
China	First Affiliated Hospital of Dalian Medical University	Dalian	Liaoning
China	The First Affiliated Hospital of Fujian Medical University	Fuzhou	Fujian
China	Guangdong Provincial Peoples Hospital	Guangzhou	Guangdong
China	The First Affiliated Hospital, Sun Yat Sen University	Guangzhou	Guangdong
China	Guizhou Provincial Peoples Hospital	Guiyang	Guizhou
China	The First Affiliated Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Zhejiang Provincial Peoples Hospital	Hangzhou	Zhejiang
China	Shandong Provincial Hospital	Jinan	Shandong
China	The First Peoples Hospital of Yunnan Province	Kunming	Yunnan
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	Zhongda Hospital Southeast University	Nanjing	Jiangsu
China	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi
China	Nanyang Central Hospital	Nanyang	Henan
China	Ningbo First Hospital	Ningbo	Zhejiang
China	The Affiliated Hospital of Qingdao University Branch South	Qingdao	Shandong
China	Rui Jin Hospital Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai
China	Shanghai General Hospital	Shanghai	Shanghai
China	Shengjing Hospital of China Medical University	Shenyang	Liaoning
China	Peking University Shenzhen Hospital	Shenzhen	Guangdong
China	The First Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	Shanxi Provincial Peoples Hospital	Taiyuan	Shanxi
China	The First Affiliated Hospital of Xinjiang Medical University	Urumqi	Xinjiang
China	Renmin Hospital of Wuhan University	Wuhan	Hubei
China	Wuxi Peoples Hospital	Wuxi	Jiangsu
China	General Hospital of Ningxia Medical University	Yinchuan	Ningxia
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan
China	Affiliated Hospital of Jiangsu University	Zhenjiang	Jiangsu
United Kingdom	Aberdeen Royal Infirmary	Aberdeen
United Kingdom	St Heliers Hospital	Carlshalton
United Kingdom	Royal Derby Hospital	Derby
United Kingdom	Aintree University Hospital	Liverpool
United Kingdom	Hammersmith Hospital	London
United Kingdom	Manchester Royal Infirmary	Manchester
United States	Northwestern University Feinberg School of Medicine	Chicago	Illinois
United States	Intermed Consultants	Edina	Minnesota
United States	Northshore University Healthsystem	Evanston	Illinois
United States	Prolato Clinical Research Center	Houston	Texas
United States	Kidney Specialist of Southern Nevada (Ksosn)	Las Vegas	Nevada
United States	Amicis Research Center	Northridge	California
United States	Stanford University	Palo Alto	California
United States	Carolina Nephrology	Spartanburg	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Countries where clinical trial is conducted

United States,  China,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Change from Baseline in Urine Protein Creatinine Ratio (UPCR)		Week 24
Primary	Part 2: Number of Participants Achieving Complete Remission		Week 104
Secondary	Part 1: Number of participants with Treatment Failure		Week 24
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Part 1: Number Of Participants with Treatment-Emergent Adverse Events (TEAEs)		Up to approximately 104 weeks
Secondary	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
Secondary	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
Secondary	Part 2: Number of participants with Treatment Failure		Week 24, Week 52, Week 76, and Week 104
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Number of Participants with = 30% Estimated Glomerular Filtration Rate (eGFR) Reduction from Baseline		Week 52 and Week 104
Secondary	Part 2: Number of Participants with TEAEs		Up to approximately 5.5 years