A Study to Examine the Efficacy and Safety of Zanubrutinib Given to Adults With Primary Membranous Nephropathy (ALMOND)

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 (PMN) 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 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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282 participants in 4 patient groups

Part 1: Zanubrutinib High Dose

Experimental group

Description:

Participants will receive zanubrutinib twice daily.

Treatment:

Drug: Zanubrutinib

Part 2: Zanubrutinib High Dose

Experimental group

Description:

Participants will receive zanubrutinib twice daily.

Treatment:

Drug: Zanubrutinib

Part 2: Zanubrutinib Low Dose

Experimental group

Description:

Participants will receive zanubrutinib once daily.

Treatment:

Drug: Zanubrutinib

Part 2: Tacrolimus

Active Comparator group

Description:

Participants will receive tacrolimus capsules twice daily for 64 weeks.

Treatment:

Drug: Tacrolimus