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

Primary Purpose

Primary Membranous Nephropathy

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Zanubrutinib
Tacrolimus
Zanubrutinib
Sponsored by
BeiGene
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Membranous Nephropathy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Biopsy-confirmed primary membranous nephropathy 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 The eGFR < 40 mL/min/1.73 m2, or initiation of dialysis 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 Positive 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.

Sites / Locations

  • Stanford UniversityRecruiting
  • Intermed ConsultantsRecruiting
  • Kidney Specialist of Southern Nevada (Ksosn)Recruiting
  • Carolina NephrologyRecruiting
  • Prolato Clinical Research CenterRecruiting
  • Beijing An Zhen Hospital of the Capital University of Medical SciencesRecruiting
  • Peking University First HospitalRecruiting
  • Peking University Peoples HospitalRecruiting
  • The First Affiliated Hospital of Fujian Medical UniversityRecruiting
  • Guangdong Provincial Peoples HospitalRecruiting
  • The First Affiliated Hospital, Sun Yat Sen UniversityRecruiting
  • Peking University Shenzhen HospitalRecruiting
  • The First Affiliated Hospital of Guangxi Medical UniversityRecruiting
  • Guizhou Provincial Peoples HospitalRecruiting
  • The First Hospital of Hebei Medical UniversityRecruiting
  • Nanyang Central HospitalRecruiting
  • The First Affiliated Hospital of Zhengzhou UniversityRecruiting
  • Renmin Hospital of Wuhan UniversityRecruiting
  • Zhongda Hospital Southeast UniversityRecruiting
  • Jiangsu Province HospitalRecruiting
  • Wuxi Peoples HospitalRecruiting
  • Affiliated Hospital of Jiangsu UniversityRecruiting
  • Shengjing Hospital of China Medical UniversityRecruiting
  • General Hospital of Ningxia Medical UniversityRecruiting
  • Shandong Provincial HospitalRecruiting
  • The Affiliated Hospital of Qingdao University Branch SouthRecruiting
  • Rui Jin Hospital Shanghai Jiao Tong University School of MedicineRecruiting
  • Shanghai General HospitalRecruiting
  • Shanxi Provincial Peoples HospitalRecruiting
  • Sichuan Academy of Medical Sciences and Sichuan Provincial Peoples HospitalRecruiting
  • The First Affiliated Hospital of Xinjiang Medical UniversityRecruiting
  • The First Peoples Hospital of Yunnan ProvinceRecruiting
  • The First Affiliated Hospital, Zhejiang University School of MedicineRecruiting
  • Zhejiang Provincial Peoples HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Active Comparator

Arm Label

Part 1 and Part 2: Zanubrutinib High dose

Part 2: Zanubrutinib Low Dose

Tacrolimus

Arm Description

Participants will receive Zanubrutinib twice daily

Participants will receive Zanubrutinib once daily

Participants will receive tacrolimus capsules for 64 weeks

Outcomes

Primary Outcome Measures

Part 1: Reduction in Urine Protein Creatinine Ratio (UPCR)
Part 2: Number of Participants Achieving Complete Remission

Secondary Outcome Measures

Part 1: Number of participants with Treatment Failure
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.
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)
Part 1: Number of Participants with Overall Remission
Participants with overall remission are those achieving either complete remission or partial remission
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
Part 1: Number Of Participants with Treatment-Emergent Adverse Events (TEAEs)
Part 2: Number of Participants with Overall Remission
Participants with overall remission are those achieving either complete remission or partial remission
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)
Part 2: Number of participants with Treatment Failure
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
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
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
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
Part 2: Health Related quality of Life (HRQoL) t Using the Kidney Disease and Quality of Life instrument™ - 36 items (KDQoL-36)
Part 2: Health Related quality of Life (HRQoL) Using European Quality of Life 5-Dimensions 5-Levels Health Questionnaire (EQ-5D-5L)
Number of Participants with ≥ 30% ReceptorEstimated Glomerular Filtration Rate (eGFR) Reduction from Baseline
Part 2: Number of Participants with TEAEs

Full Information

First Posted
January 23, 2023
Last Updated
September 26, 2023
Sponsor
BeiGene
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1. Study Identification

Unique Protocol Identification Number
NCT05707377
Brief Title
A Study to Evaluate the Safety and Efficacy of Zanubrutinib in Participants 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

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 17, 2023 (Actual)
Primary Completion Date
December 2028 (Anticipated)
Study Completion Date
December 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BeiGene

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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 who are on optimal supportive care.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Membranous Nephropathy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
This study consists of 2 parts. Part 1 will evaluate the safety and efficacy of Zanubrutinib in participants with primary membranous nephropathy. Part 2 will evaluate the safety and efficacy of zanubrutinib compared with tacrolimus.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
282 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Part 1 and Part 2: Zanubrutinib High dose
Arm Type
Experimental
Arm Description
Participants will receive Zanubrutinib twice daily
Arm Title
Part 2: Zanubrutinib Low Dose
Arm Type
Experimental
Arm Description
Participants will receive Zanubrutinib once daily
Arm Title
Tacrolimus
Arm Type
Active Comparator
Arm Description
Participants will receive tacrolimus capsules for 64 weeks
Intervention Type
Drug
Intervention Name(s)
Zanubrutinib
Other Intervention Name(s)
BGB-3111
Intervention Description
Participants will receive zanubrutinib once daily
Intervention Type
Drug
Intervention Name(s)
Tacrolimus
Intervention Description
Participants will receive tacrolimus twice daily
Intervention Type
Drug
Intervention Name(s)
Zanubrutinib
Other Intervention Name(s)
BGB-3111
Intervention Description
Participants will receive zanubrutinib twice daily
Primary Outcome Measure Information:
Title
Part 1: Reduction in Urine Protein Creatinine Ratio (UPCR)
Time Frame
Week 24
Title
Part 2: Number of Participants Achieving Complete Remission
Time Frame
Week 104
Secondary Outcome Measure Information:
Title
Part 1: Number of participants with Treatment Failure
Time Frame
Week 24
Title
Part 1: Number of Participants with Immunological Response
Description
Immunological response is defined as anti- phospholipase A2 receptor (PLA2R) antibody level reduced from baseline to less than 14 RU/ml.
Time Frame
Week 24
Title
Part 1: Number of Participants with Complete Remission
Description
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)
Time Frame
Week 24, Week 52, Week 76, and Week 104
Title
Part 1: Number of Participants with Overall Remission
Description
Participants with overall remission are those achieving either complete remission or partial remission
Time Frame
Week 24, Week 52, Week 76, and Week 104
Title
Part 1: Number of Participants with Relapse
Description
A relapse is defined as reappearance of UPCR (based on 24-hour urine collection) > 3.5 after complete or partial remission
Time Frame
Week 104
Title
Part 1: Number Of Participants with Treatment-Emergent Adverse Events (TEAEs)
Time Frame
Up to approximately 104 weeks
Title
Part 2: Number of Participants with Overall Remission
Description
Participants with overall remission are those achieving either complete remission or partial remission
Time Frame
Week 24, Week 52, Week 76, and Week 104
Title
Part 2: Number of Participants with Complete Remission
Description
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)
Time Frame
Week 24, Week 52, and Week 76
Title
Part 2: Number of participants with Treatment Failure
Time Frame
Week 24, Week 52, Week 76, and Week 104
Title
Part 2: Time to First Complete Remission
Description
Time to First Complete Remission is the time from the date of randomization to the date of the first complete remission
Time Frame
Up to approximately 5.5 years
Title
Part 2: Time to First Overall Remission
Description
Time to first overall remission is the time from the date of randomization to the date of the first overall remission
Time Frame
Up to approximately 5.5 years
Title
Part 2: Number of Participants with Relapse
Description
A relapse is defined as reappearance of UPCR (based on 24-hour urine collection) > 3.5 after complete or partial remission
Time Frame
Week 104
Title
Part 2: Time to First Relapse
Description
Time to first relapse is the time from the date of first complete or partial remission to the date of the first relapse
Time Frame
Up to approximately 5.5 years
Title
Part 2: Health Related quality of Life (HRQoL) t Using the Kidney Disease and Quality of Life instrument™ - 36 items (KDQoL-36)
Time Frame
Up to approximately 5.5 years
Title
Part 2: Health Related quality of Life (HRQoL) Using European Quality of Life 5-Dimensions 5-Levels Health Questionnaire (EQ-5D-5L)
Time Frame
Up to approximately 5.5 years
Title
Number of Participants with ≥ 30% ReceptorEstimated Glomerular Filtration Rate (eGFR) Reduction from Baseline
Time Frame
Week 52 and Week 104
Title
Part 2: Number of Participants with TEAEs
Time Frame
Up to approximately 5.5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Biopsy-confirmed primary membranous nephropathy 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 The eGFR < 40 mL/min/1.73 m2, or initiation of dialysis 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 Positive 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Study Director
Phone
1-877-828-5568
Email
clinicaltrials@beigene.com
Facility Information:
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Individual Site Status
Recruiting
Facility Name
Intermed Consultants
City
Edina
State/Province
Minnesota
ZIP/Postal Code
55435
Country
United States
Individual Site Status
Recruiting
Facility Name
Kidney Specialist of Southern Nevada (Ksosn)
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89106
Country
United States
Individual Site Status
Recruiting
Facility Name
Carolina Nephrology
City
Spartanburg
State/Province
South Carolina
ZIP/Postal Code
29306
Country
United States
Individual Site Status
Recruiting
Facility Name
Prolato Clinical Research Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77054
Country
United States
Individual Site Status
Recruiting
Facility Name
Beijing An Zhen Hospital of the Capital University of Medical Sciences
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100029
Country
China
Individual Site Status
Recruiting
Facility Name
Peking University First Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100034
Country
China
Individual Site Status
Recruiting
Facility Name
Peking University Peoples Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100044
Country
China
Individual Site Status
Recruiting
Facility Name
The First Affiliated Hospital of Fujian Medical University
City
Fuzhou
State/Province
Fujian
ZIP/Postal Code
350005
Country
China
Individual Site Status
Recruiting
Facility Name
Guangdong Provincial Peoples Hospital
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510080
Country
China
Individual Site Status
Recruiting
Facility Name
The First Affiliated Hospital, Sun Yat Sen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510080
Country
China
Individual Site Status
Recruiting
Facility Name
Peking University Shenzhen Hospital
City
Shenzhen
State/Province
Guangdong
ZIP/Postal Code
518036
Country
China
Individual Site Status
Recruiting
Facility Name
The First Affiliated Hospital of Guangxi Medical University
City
Nanning
State/Province
Guangxi
ZIP/Postal Code
530021
Country
China
Individual Site Status
Recruiting
Facility Name
Guizhou Provincial Peoples Hospital
City
Guiyang
State/Province
Guizhou
ZIP/Postal Code
550002
Country
China
Individual Site Status
Recruiting
Facility Name
The First Hospital of Hebei Medical University
City
Shijiazhuang
State/Province
Hebei
ZIP/Postal Code
50000
Country
China
Individual Site Status
Recruiting
Facility Name
Nanyang Central Hospital
City
Nanyang
State/Province
Henan
ZIP/Postal Code
473000
Country
China
Individual Site Status
Recruiting
Facility Name
The First Affiliated Hospital of Zhengzhou University
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
450052
Country
China
Individual Site Status
Recruiting
Facility Name
Renmin Hospital of Wuhan University
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430060
Country
China
Individual Site Status
Recruiting
Facility Name
Zhongda Hospital Southeast University
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210009
Country
China
Individual Site Status
Recruiting
Facility Name
Jiangsu Province Hospital
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210029
Country
China
Individual Site Status
Recruiting
Facility Name
Wuxi Peoples Hospital
City
Wuxi
State/Province
Jiangsu
ZIP/Postal Code
214023
Country
China
Individual Site Status
Recruiting
Facility Name
Affiliated Hospital of Jiangsu University
City
Zhenjiang
State/Province
Jiangsu
ZIP/Postal Code
212001
Country
China
Individual Site Status
Recruiting
Facility Name
Shengjing Hospital of China Medical University
City
Shenyang
State/Province
Liaoning
ZIP/Postal Code
110004
Country
China
Individual Site Status
Recruiting
Facility Name
General Hospital of Ningxia Medical University
City
Yinchuan
State/Province
Ningxia
ZIP/Postal Code
750004
Country
China
Individual Site Status
Recruiting
Facility Name
Shandong Provincial Hospital
City
Jinan
State/Province
Shandong
ZIP/Postal Code
250021
Country
China
Individual Site Status
Recruiting
Facility Name
The Affiliated Hospital of Qingdao University Branch South
City
Qingdao
State/Province
Shandong
ZIP/Postal Code
266000
Country
China
Individual Site Status
Recruiting
Facility Name
Rui Jin Hospital Shanghai Jiao Tong University School of Medicine
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200025
Country
China
Individual Site Status
Recruiting
Facility Name
Shanghai General Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200080
Country
China
Individual Site Status
Recruiting
Facility Name
Shanxi Provincial Peoples Hospital
City
Taiyuan
State/Province
Shanxi
ZIP/Postal Code
030012
Country
China
Individual Site Status
Recruiting
Facility Name
Sichuan Academy of Medical Sciences and Sichuan Provincial Peoples Hospital
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610071
Country
China
Individual Site Status
Recruiting
Facility Name
The First Affiliated Hospital of Xinjiang Medical University
City
Urumqi
State/Province
Xinjiang
ZIP/Postal Code
830054
Country
China
Individual Site Status
Recruiting
Facility Name
The First Peoples Hospital of Yunnan Province
City
Kunming
State/Province
Yunnan
ZIP/Postal Code
650034
Country
China
Individual Site Status
Recruiting
Facility Name
The First Affiliated Hospital, Zhejiang University School of Medicine
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310003
Country
China
Individual Site Status
Recruiting
Facility Name
Zhejiang Provincial Peoples Hospital
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310014
Country
China
Individual Site Status
Recruiting

12. IPD Sharing Statement

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

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