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

BeOne Medicines

Status and phase: Active, not recruiting; 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.

Full description

Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.

Enrollment: 178 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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178 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