Zanubrutinib for Primary Membranous Nephropathy

(ALMOND Trial)

Not currently recruiting at 103 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: BeOne Medicines

Must be taking: ACE inhibitors, ARBs

Disqualifiers: Diabetes, Severe renal disease, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of zanubrutinib for individuals with primary membranous nephropathy (PMN), a kidney condition that causes high protein levels in the urine. Part 1 of the trial will assess whether zanubrutinib can reduce protein levels in the urine. Part 2 will compare zanubrutinib to tacrolimus, an immunosuppressant, to determine which is more effective at achieving complete remission. Suitable candidates for this trial have had a kidney biopsy confirming PMN within the last 5 years and continue to experience high protein levels in their urine despite taking certain blood pressure medications. As a Phase 2, Phase 3 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to advancing treatment options.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must have been on a stable dose of an ACE inhibitor or ARB for at least 24 weeks before joining the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that zanubrutinib is usually well tolerated by people with primary membranous nephropathy (PMN). In earlier studies, most participants experienced only mild side effects. However, about 13% faced serious side effects related to the treatment, with only one case directly linked to zanubrutinib. While zanubrutinib is safe for most, some risks exist. Participants should consider these risks when deciding to join the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about zanubrutinib for primary membranous nephropathy because it offers a novel approach compared to standard treatments like corticosteroids and immunosuppressants. Unlike these traditional options, zanubrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor, targeting a specific enzyme involved in the immune response, which could lead to more precise and potentially fewer side effects. Additionally, zanubrutinib is available in both high and low doses, providing flexibility in treatment intensity based on patient needs. This innovative mechanism and dosing flexibility make zanubrutinib a promising candidate for improving outcomes in patients with this kidney condition.

What evidence suggests that this trial's treatments could be effective for primary membranous nephropathy?

Research shows that zanubrutinib may help treat primary membranous nephropathy (PMN). Early results suggest that this medication can lower protein levels in urine, indicating improved kidney function. Studies have found zanubrutinib to be generally safe for patients with PMN. By targeting specific parts of the immune system, zanubrutinib might help reduce kidney damage. Overall, these early findings are promising for those considering this treatment. Participants in this trial will receive either a high or low dose of zanubrutinib, or tacrolimus as a comparator. ^{2 3 6 7 8}

Who Is on the Research Team?

Study Director

Principal Investigator

BeOne Medicines

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

The amount of protein in your urine is too high.

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

My kidney disease was confirmed by a biopsy.

Exclusion Criteria

My liver is not working well (severe issues).

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

You have tuberculosis when tested before the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants receive zanubrutinib to evaluate efficacy as measured by proteinuria reduction

24 weeks

Treatment Part 2

Participants receive zanubrutinib or tacrolimus to evaluate efficacy as measured by complete remission rate

64 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

40 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Tacrolimus
• Zanubrutinib

Trial Overview 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.

How Is the Trial Designed?

Group I: Part 2: Zanubrutinib Low Dose Experimental Treatment 1 Intervention

Participants will receive zanubrutinib once daily.

Group II: Part 2: Zanubrutinib High Dose Experimental Treatment 1 Intervention

Participants will receive zanubrutinib twice daily.

Group III: Part 1: Zanubrutinib High Dose Experimental Treatment 1 Intervention

Participants will receive zanubrutinib twice daily.

Group IV: Part 2: Tacrolimus Active Control 1 Intervention

Participants will receive tacrolimus capsules twice daily for 64 weeks.

Zanubrutinib is already approved in United States, China for the following indications:

Approved in United States as Brukinsa for:

• Chronic lymphocytic leukemia (CLL)
• Small lymphocytic lymphoma (SLL)

Approved in China as Brukinsa for:

• Chronic lymphocytic leukemia (CLL)
• Small lymphocytic lymphoma (SLL)

Who Is Running the Clinical Trial?

BeOne Medicines

Lead Sponsor

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Published Research Related to This Trial

Primary membranous nephropathy, primarily caused by anti-PLA2R antibodies, is the leading cause of nephrotic syndrome in adults, and recent studies indicate that biological agents targeting autoantibody-producing cells can effectively manage the disease with a good safety profile.

The review proposes a diagnostic and therapeutic algorithm for managing primary membranous nephropathy, comparing the efficacy and safety of treatments like rituximab and highlighting the need for further advancements in clinical care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary membranous nephropathy in the era of autoantibodies and biological therapies. Rojas-Rivera, JE., Ortiz Arduán, A.[2021]

In a small phase II trial involving 9 patients with lupus membranous nephropathy, filgotinib showed a significant median reduction of 50.7% in 24-hour urine protein after 16 weeks, suggesting potential efficacy in treating this condition.

Filgotinib was well tolerated by patients, while the results for lanraplenib were inconclusive due to the limited number of participants, indicating that further research on JAK inhibitors like filgotinib is warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II, randomised, double-blind, multicentre study evaluating the safety and efficacy of filgotinib and lanraplenib in patients with lupus membranous nephropathy. Baker, M., Chaichian, Y., Genovese, M., et al.[2022]

In a study of 3 patients with primary membranous nephropathy who were resistant to or could not tolerate steroids, treatment with tacrolimus for 6 months resulted in significant reductions in proteinuria, with one patient experiencing almost complete disappearance of proteinuria.

Although proteinuria increased again in 2 patients after stopping tacrolimus, it did not return to pretreatment levels, suggesting that tacrolimus may provide a modest and lasting benefit in managing resistant membranous nephropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tacrolimus in resistant primary membranous nephropathy--a report of 3 cases. Szeto, CC., Leung, CB., Lai, FM., et al.[2019]

Recent advancements in understanding membranous nephropathy have led to improved molecular diagnoses through the identification of target antigens, which helps in monitoring disease progression and guiding treatment decisions.

Rituximab, a B-cell-depleting agent, has emerged as a leading treatment option for primary membranous nephropathy, showing promise in randomized controlled trials compared to traditional immunosuppressive therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Membranous Nephropathy: Core Curriculum 2021. Alsharhan, L., Beck, LH.[2021]

In a pilot study involving 13 high-risk patients with severe membranous nephropathy, a novel treatment combining rituximab and cyclosporine led to a significant reduction in proteinuria, with a 65% decrease at 3 months and 80% at 6 months.

The treatment resulted in a high remission rate, with 92% of patients achieving complete or partial remission by 9 months, and 54% achieving complete remission by 12 months, while maintaining stable renal function and showing good tolerance to the regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Membranous nephropathy: Pilot study of a novel regimen combining cyclosporine and Rituximab. Waldman, M., Beck, LH., Braun, M., et al.[2020]

In a 2-year study involving patients with idiopathic membranous nephropathy and steroid-resistant nephrotic syndrome, the combination of mizoribine (MZR) and prednisolone (PSL) led to a complete remission rate of 52.6% in the once-a-day MZR group compared to 38.9% in the three-times-a-day group, indicating that once-daily dosing may be more effective.

The study found that achieving a peak serum concentration (C max) of MZR greater than 1.1 µg/mL was necessary for complete remission, highlighting the importance of monitoring drug levels to optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mizoribine therapy combined with steroids and mizoribine blood concentration monitoring for idiopathic membranous nephropathy with steroid-resistant nephrotic syndrome. Saito, T., Iwano, M., Matsumoto, K., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05707377

NCT05707377 | A Study to Examine the Efficacy and ... A Study to Examine the Efficacy and Safety of Zanubrutinib Given to Adults With Primary Membranous Nephropathy (ALMOND) · Study Overview · Contacts and Locations.

2. beonemedinfo.com beonemedinfo.com/CongressDocuments/Lafayette_BGB-3111-309_ASNKidneyWeek_Poster_2024.pdf

Zanubrutinib for the Treatment of Primary Membranous ... Part 1 was an open-label, single-arm study investigating the preliminary efficacy and safety of zanubrutinib in the treatment of PMN (Figure ...

3. asn-online.org asn-online.org/education/kidneyweek/2024/program-abstract.aspx?controlId=4164844

Kidney Week Zanubrutinib appears to be generally well tolerated and shows activity in pts with PMN.

4. withpower.com withpower.com/trial/phase-2-and-3-kidney-diseases-3-2023-7e452

Zanubrutinib for Primary Membranous Nephropathy This trial tests zanubrutinib, a medication aimed at reducing kidney damage, in patients with a specific kidney disease. It measures how well it lowers ...

5. clinicaltrials.eu clinicaltrials.eu/trial/study-of-zanubrutinib-and-tacrolimus-for-patients-with-primary-membranous-nephropathy/

Study of Zanubrutinib and Tacrolimus for Patients with ... The study aims to provide valuable information on the potential benefits of Zanubrutinib for people with Primary Membranous Nephropathy.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05707377

NCT05707377 | A Study to Examine the Efficacy and ... A Phase 2/3, Multicenter, Randomized, Active-Controlled, Open-label Study to Evaluate the Efficacy and Safety of Zanubrutinib in Patients With Primary ...

7. beonemedicines.com beonemedicines.com/clinical-trials/a-study-to-evaluate-the-safety-and-efficacy-of-zanubrutinib-in-participants-with-primary-membranous-nephropathy/

BGB-3111-309 A study to examine the efficacy and safety of zanubrutinib given to adults with primary membranous nephropathy.

8. go.drugbank.com go.drugbank.com/drugs/DB15035/clinical_trials?conditions=DBCOND0036528%2CDBCOND0134549&phase=2&purpose=treatment&status=recruiting

Zanubrutinib Recruiting Phase 2 Trials for Primary ... A Study to Examine the Efficacy and Safety of Zanubrutinib Given to Adults With Primary Membranous Nephropathy ... data requires a license and proper citations.