Clinical Trials for Membranous Nephropathy
There are currently 7 ongoing clinical trials investigating new treatments for membranous nephropathy, a kidney disease where the immune system damages the kidney’s filtering units. These studies are testing various medications including dapagliflozin, zanubrutinib, AP1189, atacicept, felzartamab, and obinutuzumab across multiple European countries. (Also known as: Glomerulonephritis membranous, Primary Membranous Nephropathy, Idiopathic Membranous Nephropathy)
Clinical trial locations
- Belgium
- Czechia
- Denmark
- France
- Germany
- Italy
- Study of Zanubrutinib and Tacrolimus for Patients with Primary Membranous Nephropathy
- Study of Atacicept Treatment for Patients with Multiple Autoimmune Glomerular Diseases
- Study of Felzartamab for Patients with Membranous Nephropathy Resistant to Anti-CD20 Therapy
- Study of Obinutuzumab for Patients with Primary Membranous Nephropathy Resistant or Intolerant to Rituximab
- Study on the Effectiveness and Safety of Obinutuzumab and Tacrolimus for Patients with Primary Membranous Nephropathy
- Poland
- Spain
- Sweden
Evaluating Dapagliflozin’s Effect on Immune Activity in Patients with Membranous Nephropathy
This study is investigating dapagliflozin, a medication typically used for diabetes and kidney disease, to see if it can help regulate immune activity in patients experiencing an immunological relapse of membranous nephropathy. The trial will monitor participants over 6 months while they continue their existing treatment and add dapagliflozin to their regimen.
Who can participate: Adults between 18 and 84 years old with membranous nephropathy who have anti-PLA2R1 autoantibodies in their blood. Participants must have experienced an immunological relapse, meaning their antibody levels increased by more than 14 RU/mL after a period of control. Their urine protein-to-creatinine ratio must be between 0.5 and 3.5 g/g, and they must be on a stable dose of medication to reduce protein in their urine.
Who cannot participate: Individuals younger than 18 years old, pregnant women or those planning to become pregnant, people who are breastfeeding, those with type 1 diabetes, urinary or genital tract infections, severe liver problems, known allergies to dapagliflozin, those currently in another clinical trial, people unable to provide informed consent, and those who received other treatments for membranous nephropathy within the last 6 months.
Study goals: The main goal is to evaluate whether dapagliflozin can reduce the levels of anti-PLA2R1 antibodies that attack the kidneys. Researchers will also track changes in protein levels in the urine, blood albumin levels, kidney function, and various immune system signaling molecules called cytokines. The study will monitor both the effectiveness of the treatment and its safety and tolerance.
Investigational drug: Dapagliflozin is an SGLT2 inhibitor that helps the kidneys remove excess sugar from the blood through urine. In this trial, researchers are studying whether it can help regulate immune system activity and reduce harmful antibodies in people with membranous nephropathy.
Study of Zanubrutinib and Tacrolimus for Patients with Primary Membranous Nephropathy
This two-part study compares the effectiveness and safety of zanubrutinib with tacrolimus in patients with primary membranous nephropathy. The first part evaluates how zanubrutinib reduces protein loss in urine over 24 weeks. The second part randomly assigns participants to receive either zanubrutinib or tacrolimus to compare their effectiveness in achieving complete remission over 104 weeks.
Who can participate: Adults between 18 and 75 years old with a confirmed diagnosis of primary membranous nephropathy through a kidney biopsy within the last 5 years. Participants must have a UPCR greater than 3.5 based on a 24-hour urine collection. For Part 1, participants must have been treated with blood pressure medications for at least 12 weeks and have anti-PLA2R antibody levels greater than 50 RU/mL. Female participants who can have children must use highly effective birth control, and male participants must use barrier contraception.
Who cannot participate: Patients with other serious health conditions that could interfere with the study, pregnant or breastfeeding women, those with recent infections requiring treatment, those with a history of cancer (except certain skin cancers), those currently using medications that could affect study results, those with known allergies to the study medication, those who participated in another clinical trial within the last 30 days, those with a history of drug or alcohol abuse, those with immune system conditions, and those who have had a kidney transplant.
Study goals: The study aims to evaluate whether zanubrutinib can effectively reduce protein in the urine and achieve complete remission. It will compare the effectiveness of zanubrutinib against tacrolimus in helping patients achieve remission, tracking the time to first remission and any potential relapses.
Investigational drugs: Zanubrutinib is being studied for its ability to reduce proteinuria by inhibiting Bruton’s tyrosine kinase, which plays a role in the immune system and inflammation. Tacrolimus is used as a comparison medication and works by suppressing the immune system to help achieve complete remission.
Study on the Safety and Effects of AP1189 for Patients with Idiopathic Membranous Nephropathy and Severe Proteinuria
This trial is testing a new treatment called AP1189 tablet, which contains the active substance resomelagon. The study compares AP1189 to a placebo when used alongside standard treatments like ACE inhibitors or angiotensin II receptor blockers over a 12-week period.
Who can participate: Adults between 18 and 85 years old with idiopathic membranous nephropathy and severe proteinuria. Participants must be diagnosed as anti-PLA2-Receptor positive within 6 months before joining or have a kidney biopsy consistent with the condition within 24 months. They must have severe proteinuria defined by a U-protein/creatinine ratio greater than 3.0 g/g and/or U-albumin/creatinine ratio greater than 2.0 g/g, with blood albumin below normal limits. Kidney function must show an eGFR greater than 30 ml/min/1.73m2. Participants should have been treated with ACE inhibitors or angiotensin II receptor blockers for at least 1 month with stable blood pressure, or these treatments must have been excluded due to side effects.
Who cannot participate: Patients with any other kidney disease besides idiopathic membranous nephropathy, those not within the specified age range, members of vulnerable populations, those with medical conditions or taking medications that might interfere with results, recent participants in other clinical trials, those with serious allergic reactions to study medications, pregnant or breastfeeding women, and those with any condition that study doctors believe would make participation unsafe.
Study goals: The study aims to evaluate the safety and effectiveness of the AP1189 tablet in reducing protein loss in urine over 12 weeks. Researchers will monitor participants’ health by checking for side effects, changes in vital signs, and conducting various tests. The main focus is on how the treatment affects protein levels in urine, albumin levels in blood, and kidney filtration rates.
Investigational drug: AP1189 is being tested as an additional treatment for patients already on ACE inhibitors or angiotensin II receptor blockers. It works by modulating certain pathways in the body to help reduce inflammation and improve kidney function, and is classified as an anti-inflammatory agent.
Study of Atacicept Treatment for Patients with Multiple Autoimmune Glomerular Diseases
This study is testing atacicept in people with various autoimmune kidney diseases, including membranous nephropathy, IgA nephropathy, minimal change disease, and focal segmental glomerulosclerosis. The medication is given as a subcutaneous injection while participants continue their regular standard of care medications over a 52-week period.
Who can participate: Participants must be currently receiving stable standard of care treatment according to local guidelines. Blood pressure must be controlled (systolic ≤160 mmHg and diastolic ≤90 mmHg for adults, or below the 95th percentile for those aged 10-17). Participants must weigh at least 40 kilograms and agree to follow contraceptive guidelines. For membranous nephropathy specifically, participants must be 18 years or older, have biopsy-confirmed disease with anti-PLA2R antibodies ≥25 RU/mL, and have protein in urine of at least 1.5 grams per gram of creatinine.
Who cannot participate: Those below 18 or above 75 years of age, people with known severe allergies to atacicept, pregnant or breastfeeding women, those with severe kidney dysfunction (eGFR below 30), those with active or chronic infections including hepatitis B, hepatitis C, or HIV, those with a history of cancer within the past 5 years (except successfully treated non-melanoma skin cancer), those who had major surgery within 8 weeks, people with uncontrolled high blood pressure, severe heart disease, active liver disease, recent use of other investigational drugs, history of drug or alcohol abuse within the past year, or mental conditions that could interfere with participation.
Study goals: The study aims to evaluate the safety of atacicept and its effectiveness in reducing protein in the urine. Researchers will monitor kidney function, particularly proteinuria levels and how well the kidneys filter blood, along with tracking specific disease markers in the blood associated with each type of kidney disease.
Investigational drug: Atacicept is a biological medication that works by targeting and inhibiting two important proteins involved in B-cell development and autoimmune responses. It reduces the production of harmful antibodies that can damage the kidneys, potentially helping to decrease protein leakage into urine.
Study of Felzartamab for Patients with Membranous Nephropathy Resistant to Anti-CD20 Therapy
This trial is testing felzartamab, a monoclonal antibody given through infusion, for patients with membranous nephropathy who have not responded well to previous anti-CD20 treatments. The study lasts up to 24 months and aims to see if felzartamab can reduce protein levels in the urine.
Who can participate: Adults at least 18 years old with a confirmed diagnosis of membranous nephropathy through kidney biopsy (with or without anti-PLA2R or anti-THSD7A antibodies). Participants must be on treatment with medications that block the renin-angiotensin system at the highest tolerable dose, with well-controlled blood pressure (below 140/90 mmHg in at least three checks). Participants must have either shown resistance to anti-CD20 treatment (still having high protein levels in urine at least 12 months after therapy) or dependence on anti-CD20 treatment (frequent relapses despite repeated treatments). Kidney function must show an eGFR greater than 30 ml/min/1.73m², and less than 50% of kidney filtering units should be scarred. Anti-CD20 therapy must have been stopped for at least 12 months, and no immunosuppressive therapy should have been used in the last 6 months. Participants must have completed COVID-19 vaccination.
Who cannot participate: Patients with other serious kidney diseases besides membranous nephropathy, those who have had a kidney transplant, those currently receiving other experimental drugs, those with a history of severe allergic reactions to similar treatments, pregnant or breastfeeding women, those with uncontrolled high blood pressure, active infections requiring treatment, a history of cancer within the last five years (except certain skin cancers), a history of drug or alcohol abuse within the last year, or any other medical condition that would make participation unsafe.
Study goals: The study aims to determine if felzartamab can effectively reduce protein levels in the urine and achieve complete or partial remission of nephrotic syndrome. Researchers will monitor various aspects of kidney function and track disease-specific antibody levels throughout the 24-month period.
Investigational drug: Felzartamab is a human antibody that targets a protein called CD38. It is being studied as a rescue therapy for patients who have not responded to previous CD20-targeting treatments, with the goal of reducing excessive protein loss in the urine.
Study of Obinutuzumab for Patients with Primary Membranous Nephropathy Resistant or Intolerant to Rituximab
This study is testing obinutuzumab in patients with primary membranous nephropathy who have either not responded well to rituximab, are dependent on it, or cannot tolerate it due to severe side effects. The medication is given as an infusion to see if it can help patients achieve remission of nephrotic syndrome.
Who can participate: Adults 18 years or older with biopsy-proven primary membranous nephropathy. Participants must have a recent kidney biopsy (within the last six months) to confirm diagnosis and assess disease severity. They must be at high risk of disease progression due to persistent high protein levels in urine despite treatment with ACE inhibitors or ARBs at the highest tolerated doses for at least six months. Participants must have failed to respond to rituximab therapy due to intolerance (severe allergic reactions), resistance (no improvement after treatment), or dependence (frequent relapses despite initial improvement). Kidney function must show an eGFR of at least 30 mL/min/1.73 m². Participants must agree to use effective contraception from 28 days before starting treatment until 18 months after stopping treatment.
Who cannot participate: Patients allergic to or having bad reactions to rituximab, those who do not respond to rituximab or need it regularly to manage their condition, those unable to tolerate obinutuzumab, pregnant or breastfeeding women, those with other serious health conditions that might interfere with the study, and members of vulnerable populations unable to give informed consent.
Study goals: The study aims to evaluate if obinutuzumab can help reduce symptoms of nephrotic syndrome and achieve remission. It will assess both complete and partial remission rates, along with monitoring the safety and tolerability of the treatment. Regular follow-ups will monitor protein levels in urine and blood, as well as other health indicators.
Investigational drug: Obinutuzumab is administered as an intravenous infusion. It works by targeting and binding to a specific protein on the surface of certain immune cells, leading to their destruction. It is classified as a monoclonal antibody.
Study on the Effectiveness and Safety of Obinutuzumab and Tacrolimus for Patients with Primary Membranous Nephropathy
This study compares obinutuzumab, given as an infusion, with tacrolimus, taken orally as capsules, over a 104-week period. The study aims to determine how well obinutuzumab works compared to tacrolimus in helping patients achieve complete remission of primary membranous nephropathy.
Who can participate: Adults with a diagnosis of primary membranous nephropathy confirmed by kidney biopsy either before or during the screening process. Participants must have a urinary protein-to-creatinine ratio (UPCR) of at least 5 grams per gram from a 24-hour urine collection after receiving the best supportive care for at least 3 months before screening, or a UPCR of at least 4 grams per gram after 6 months of best supportive care. Kidney function must show an eGFR of at least 40 mL/min/1.73 m² or endogenous creatinine clearance of at least 40 mL/min/1.73 m². Patients who previously responded to certain treatments and then had the disease return can participate if they stopped using calcineurin inhibitors or alkylating agents for at least 6 months and rituximab for at least 9 months before screening. Both male and female participants are eligible.
Who cannot participate: Patients with a different kidney condition other than primary membranous nephropathy, those not within the specified age range, those unable to follow study procedures or take medications as required, those with other serious health conditions that might interfere with the study, pregnant or breastfeeding women, those who participated in another clinical trial recently, those with allergies to study medications, and those unable to provide informed consent.
Study goals: The primary goal is to achieve complete remission by Week 104, which involves a significant reduction in protein levels in the urine and stabilization of kidney function. The study will also evaluate overall remission rates, time to treatment failure, and changes in fatigue and physical health as reported by patients. Long-term effects including duration of remission and any adverse events will also be assessed.
Investigational drugs: Obinutuzumab targets and binds to specific cells in the immune system, helping to reduce inflammation and kidney damage. Tacrolimus works by suppressing the immune system to prevent it from attacking the body’s own tissues. Both are being compared for their effectiveness in achieving complete remission.
Summary
These seven clinical trials represent a diverse approach to treating membranous nephropathy, with studies distributed across multiple European countries. Italy stands out as a location for five trials, followed by France, Poland, and Spain, each hosting three trials. The studies investigate six different investigational drugs: dapagliflozin, zanubrutinib, AP1189, atacicept, felzartamab, and obinutuzumab, with some studies comparing new treatments to existing medications like tacrolimus.
A notable pattern emerges in the focus on patients who have not responded well to conventional treatments, particularly rituximab and other anti-CD20 therapies. Three trials specifically target patients resistant to, dependent on, or intolerant of these standard treatments, highlighting an important unmet medical need. The studies vary in duration from 12 weeks to 104 weeks, allowing researchers to evaluate both short-term safety and long-term effectiveness.
Most trials focus on reducing protein in the urine as the primary goal, with secondary aims including achieving complete or partial remission of symptoms and monitoring kidney function. Several studies also investigate how treatments affect specific antibodies like anti-PLA2R1, which are associated with the autoimmune attack on the kidneys. The trials employ various approaches, including targeting different parts of the immune system and adding new medications to existing standard treatments, offering hope for patients with this challenging kidney condition.
