Zanubrutinib for Primary Membranous Nephropathy
(ALMOND Trial)
Recruiting in Palo Alto (17 mi)
+101 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
Sponsor: BeiGene
Must be taking: ACE inhibitors, ARBs
Disqualifiers: Diabetes, Severe renal disease, HIV, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?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.
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.
What data supports the effectiveness of the drug Zanubrutinib for primary membranous nephropathy?
While there is no direct evidence for Zanubrutinib in primary membranous nephropathy, studies have shown that targeting autoantibody-producing cells with biological agents can be effective in controlling the disease. Tacrolimus, another drug mentioned, has been studied for its efficacy and safety in primary membranous nephropathy, suggesting potential benefits in managing the condition.
12345How is the drug Zanubrutinib different from other treatments for primary membranous nephropathy?
Zanubrutinib is unique because it is a Bruton tyrosine kinase (BTK) inhibitor, which targets specific pathways in the immune system that are involved in the production of harmful antibodies, potentially offering a new approach compared to traditional immunosuppressive treatments like rituximab or steroids.
12356Eligibility Criteria
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.
+1 more
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.
+5 more
Trial Timeline
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
Participant Groups
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.
4Treatment groups
Experimental Treatment
Active Control
Group I: Part 2: Zanubrutinib Low DoseExperimental Treatment1 Intervention
Participants will receive zanubrutinib once daily.
Group II: Part 2: Zanubrutinib High DoseExperimental Treatment1 Intervention
Participants will receive zanubrutinib twice daily.
Group III: Part 1: Zanubrutinib High DoseExperimental Treatment1 Intervention
Participants will receive zanubrutinib twice daily.
Group IV: Part 2: TacrolimusActive Control1 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)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Cincinnati Cancer CenterCincinnati, OH
Cisss de La Monteregie CentreQuebec, Canada
University of British ColumbiaVancouver, Canada
Ott Healthcare, IncScarborough, Canada
More Trial Locations
Loading ...
Who Is Running the Clinical Trial?
BeiGeneLead Sponsor
References
Membranous nephropathy: Pilot study of a novel regimen combining cyclosporine and Rituximab. [2020]There is broad consensus that high grade basal proteinuria and failure to achieve remission of proteinuria are key determinants of adverse renal prognosis in patients with primary membranous nephropathy. Based on the fact that current regimens are not ideal due to short and long-term toxicity and propensity to relapse after treatment withdrawal, we developed a treatment protocol based on a novel combination of rituximab and cyclosporine which targets both the B and T cell limbs of the immune system. Herein, we report pilot study data on proteinuria, changes in autoantibody levels and renal function that offer a potentially effective new approach to treatment of severe membranous nephropathy.
Primary membranous nephropathy in the era of autoantibodies and biological therapies. [2021]Primary membranous nephropathy is an autoimmune kidney disease and the most common cause of nephrotic syndrome in adults. About 70%-80% of cases are caused by anti-PLA2R antibodies. Its association with anti-THSD7A antibodies and other autoantibodies has also been described. Recent pilot studies and clinical trials have shown that several biological agents targeting autoantibody-producing cells are effective in controlling the disease with an acceptable safety profile. In this narrative review, we update key concepts about the pathogenesis, autoantibody-based diagnosis, and kidney biopsy findings in primary membranous nephropathy. In addition, we propose a diagnostic and therapeutic algorithm, including guidance on monitoring the response to therapy. We compare the efficacy and safety of currently available treatments, including rituximab and new biological agents, and identify unmet clinical needs.
Membranous Nephropathy: Core Curriculum 2021. [2021]The understanding and management of membranous nephropathy, a common cause of nephrotic syndrome that is more frequently encountered in adults than in children, has rapidly evolved over the past decade. Identification of target antigens has allowed for more precise molecular diagnoses, and the ability to monitor circulating autoantibodies has added a new vantage point in terms of disease monitoring and decisions about immunosuppression. Although immunosuppression with alkylating agents combined with corticosteroids, or with calcineurin inhibitor-based regimens, has been the historical mainstay of treatment, observational and now randomized controlled trials with the B-cell-depleting agent rituximab have moved this agent to the forefront of therapy for primary membranous nephropathy. In this Core Curriculum, we discuss the typical features of primary and secondary disease; highlight the target antigens such as the phospholipase A2 receptor, thrombospondin type 1 domain-containing 7A, neural epidermal growth factor-like 1, and semaphorin-3B; describe the relationship between the immunologic and clinical courses of disease; and review modern management with supportive care or immunosuppressive treatment based on these composite parameters.
Tacrolimus in resistant primary membranous nephropathy--a report of 3 cases. [2019]To study the efficacy and safety of tacrolimus in primary membranous nephropathy.
Phase II, randomised, double-blind, multicentre study evaluating the safety and efficacy of filgotinib and lanraplenib in patients with lupus membranous nephropathy. [2022]Patients with lupus membranous nephropathy (LMN) are at risk for prolonged proteinuria and progressive chronic kidney disease. There are no proven effective treatments for LMN, and controlled trials are lacking. This trial assessed the preferential Janus kinase 1 (JAK1) inhibitor filgotinib and the spleen tyrosine kinase inhibitor lanraplenib in patients with LMN.
Mizoribine therapy combined with steroids and mizoribine blood concentration monitoring for idiopathic membranous nephropathy with steroid-resistant nephrotic syndrome. [2022]We designed a prospective and randomized trial of mizoribine (MZR) therapy combined with prednisolone (PSL) for idiopathic membranous nephropathy (IMN) with steroid-resistant nephrotic syndrome (SRNS).