A Study to Evaluate the Safety and Efficacy of Zanubrutinib in Participants With Primary Membranous Nephropathy
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2/Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part 1 and Part 2: Zanubrutinib High dose Participants will receive Zanubrutinib twice daily |
Drug: Zanubrutinib
Participants will receive zanubritinib twice daily
Other Names:
|
| Experimental: Part 2: Zanubrutinib Low Dose Participants will receive Zanubrutinib once daily |
Drug: Zanubrutinib
Participants will receive zanubrutinib once daily
Other Names:
|
| Active Comparator: Tacrolimus Participants will receive tacrolimus capsules for 64 weeks |
Drug: Tacrolimus
Participants will receive tacrolimus twice daily
|
Outcome Measures
Primary Outcome Measures
- Part 1: Reduction in Urine Protein Creatinine Ratio (UPCR) [Week 24]
- Part 2: Number of Participants Achieving Complete Remission [Week 104]
Secondary Outcome Measures
- 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 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) [Up to approximately 104 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 5.5 years]
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 5.5 years]
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 5.5 years]
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) he Kidney Disease and Quality of Life instrument™ - 36 items (KDQoL-36) [Up to approximately 5.5 years]
- 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]
- Number of Participants with ≥ 30% Epidermal Growth Factor Receptor (eGFR) Reduction from Baseline [Week 52 and Week 104]
- Part 2: Number of Participants with TEAEs [Up to approximately 5.5 years]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Participants with a secondary cause of membranous nephropathy
-
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:
-
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.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- BeiGene
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BGB-3111-309