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

BeiGene

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Primary Membranous Nephropathy

Treatments: Drug: Tacrolimus; Drug: Zanubrutinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT05707377

CTR20230546 (Registry Identifier)

BGB-3111-309

2022-501147-32-00 (Registry Identifier)

Details and patient eligibility

About

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.

Enrollment: 282 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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282 participants in 3 patient groups

Part 1 and Part 2: Zanubrutinib High dose

Experimental group

Description:

Participants will receive Zanubrutinib twice daily

Treatment:

Drug: Zanubrutinib

Drug: Zanubrutinib

Part 2: Zanubrutinib Low Dose

Experimental group

Description:

Participants will receive Zanubrutinib once daily

Treatment:

Drug: Zanubrutinib

Drug: Zanubrutinib

Tacrolimus

Active Comparator group

Description:

Participants will receive tacrolimus capsules for 64 weeks

Treatment:

Drug: Tacrolimus