Overview
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
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.