What side effects are associated with this type of intervention?

Common side effects of Bruton's Tyrosine Kinase inhibitors like Zanubrutinib, used in treating Primary Membranous Nephropathy, include infections, bleeding, cytopenias, and gastrointestinal issues. Other treatments, such as tacrolimus, can cause nephrotoxicity, hypertension, hyperglycemia, and neurotoxicity, while cyclophosphamide is associated with bone marrow suppression, increased risk of infections, and potential bladder toxicity.

What prior FDA approvals exist?

As of now, there are no specific FDA-approved Bruton's Tyrosine Kinase (BTK) inhibitors like Zanubrutinib for the treatment of Primary Membranous Nephropathy. Traditional treatments for this condition have included immunosuppressive therapies such as cyclophosphamide, rituximab, and calcineurin inhibitors like tacrolimus. These treatments aim to reduce proteinuria and manage symptoms. Zanubrutinib is currently being studied for its efficacy in reducing proteinuria in patients with Primary Membranous Nephropathy, which could potentially offer a new therapeutic option if proven effective.

What other types of research exist?

Promising alternatives to Zanubrutinib for Primary Membranous Nephropathy patients include Rituximab, which has been used successfully in various glomerular diseases, and Tacrolimus, which is being directly compared to Zanubrutinib in clinical studies. Additionally, VEGF-targeted treatments like Lenvatinib and Axitinib, although primarily used in cancer, have shown effects on proteinuria and could be considered under careful medical supervision.

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Bruton's Tyrosine Kinase (BTK) Inhibitor

Zanubrutinib for Primary Membranous Nephropathy

Phase 2 & 3

Recruiting

Research Sponsored by BeiGene

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

Biopsy-confirmed primary membranous nephropathy

Must not have

Severe hepatic insufficiency (Child-Pugh C)

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 5.5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests zanubrutinib, a medication aimed at reducing kidney damage, in patients with a specific kidney disease. It measures how well it lowers protein in the urine and compares its effectiveness to another drug, tacrolimus. Zanubrutinib is an oral medication approved in Europe for certain conditions and is being reviewed for approval in the United States.

Who is the study for?

This trial is for people with primary membranous nephropathy, confirmed by biopsy. They must have been treated with specific blood pressure medications (ACEI or ARB) for at least 24 weeks and have certain levels of protein in their urine. It's not open to those with secondary causes of the disease, active hepatitis B or C, severe liver issues, significant heart diseases, very low kidney function, a history of immune deficiency conditions like HIV or past spleen removals.

What is being tested?

The study tests Zanubrutinib's ability to reduce protein in urine and compares its effectiveness against Tacrolimus in achieving complete remission. Participants are already on optimal supportive care and will be divided into two parts: one focusing on Zanubrutinib alone and the other comparing it directly with Tacrolimus.

What are the potential side effects?

Potential side effects may include digestive disturbances, headaches, muscle pain, rash or bruising easily due to blood thinning effect; infections risk could increase as well since Zanubrutinib affects the immune system.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I've been on the highest dose possible of ACEI or ARB for my condition for at least 24 weeks, with controlled blood pressure.

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My kidney disease was confirmed by a biopsy.

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My anti-PLA2R antibody levels are above 50 RU/mL.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My liver is not working well (severe issues).

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I have a condition like HIV or have had my spleen removed, making me more prone to infections.

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I have serious heart or brain blood vessel problems.

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I have diabetes with an HbA1c level of 7% or higher.

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I have a kidney condition caused by another disease.

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My kidney function is low or I am on dialysis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 5.5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 5.5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 5.5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Part 1: Number of Participants with Complete Remission

Part 1: Number of Participants with Immunological Response

Part 1: Number of Participants with Overall Remission

+7 more

Side effects data

From 2024 Phase 3 trial • 652 Patients • NCT03734016

24%

Diarrhoea

20%

Hypertension

18%

Neutropenia

16%

COVID-19

16%

Arthralgia

15%

Anaemia

14%

Upper respiratory tract infection

13%

Muscle spasms

13%

Fatigue

12%

Rash

11%

Atrial fibrillation

10%

Thrombocytopenia

10%

Nausea

10%

Pyrexia

10%

Contusion

10%

Cough

10%

Headache

Pneumonia

Vomiting

Urinary tract infection

Pain in extremity

Epistaxis

Peripheral swelling

Constipation

Oedema peripheral

Back pain

Dizziness

Dyspepsia

Neutrophil count decreased

Platelet count decreased

Hyperuricaemia

Decreased appetite

Bronchitis

Petechiae

Abdominal pain

Fall

Hypokalaemia

Insomnia

Palpitations

Blood pressure increased

Dyspnoea

Gastrooesophageal reflux disease

COVID-19 pneumonia

Cellulitis

Haematuria

Sinusitis

Alanine aminotransferase increased

Weight decreased

Haematoma

Oral herpes

Myalgia

Squamous cell carcinoma of skin

Basal cell carcinoma

Anxiety

Nasopharyngitis

Gout

Oropharyngeal pain

Paronychia

Skin infection

Paraesthesia

Conjunctivitis

Mouth ulceration

Asthenia

Pharyngitis

Aspartate aminotransferase increased

Productive cough

Vertigo

Pruritus

Herpes zoster

Cataract

Blood creatinine increased

Rash maculo-papular

Hypogammaglobulinaemia

Pleural effusion

Mastoiditis

Transient ischaemic attack

Abdominal pain upper

Death

Adenocarcinoma gastric

Lung adenocarcinoma

Cerebral infarction

Syncope

Cardiac arrest

Respiratory failure

Influenza

Hypoglobulinaemia

Lymphadenopathy

Angina pectoris

Ventricular fibrillation

Inguinal hernia

Appendicitis

Infection

Pneumocystis jirovecii pneumonia

Septic shock

Haemolytic anaemia

Subdural haematoma

Acute kidney injury

Acute respiratory failure

Myocardial infarction

Skin laceration

100%

80%

60%

40%

20%

Study treatment Arm

Ibrutinib

Zanubrutinib

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: Part 2: Zanubrutinib Low DoseExperimental Treatment1 Intervention

Participants will receive Zanubrutinib once daily

Group II: Part 1 and Part 2: Zanubrutinib High doseExperimental Treatment1 Intervention

Participants will receive Zanubrutinib twice daily

Group III: TacrolimusActive Control1 Intervention

Participants will receive tacrolimus capsules for 64 weeks

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Zanubrutinib

2017

Completed Phase 3

~2160

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Primary Membranous Nephropathy (PMN) include Bruton's Tyrosine Kinase (BTK) inhibitors like Zanubrutinib, which block the BTK enzyme to reduce B-cell activity and antibody production that damages the kidneys. Other treatments involve immunosuppressive agents such as cyclophosphamide and corticosteroids, which lower the immune system's activity to prevent further kidney damage. These mechanisms are crucial for PMN patients as they help in reducing proteinuria and achieving remission, thereby preserving kidney function and improving outcomes.