Membranous Nephropathy - PLA2R InducedPhase 2/3NCT07163611
Obinutuzumab Induced Decreases of PLA2R Antibodies in Membranous Nephropathy: a Pilot Study
A Phase 2/3 study testing Obinutuzumab administration in people with Membranous Nephropathy - PLA2R Induced, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
Objective: To assess the disappearance rate (half-life) of anti-PLA2R antibodies in high-risk primary membranous nephropathy (pMN) patients treated with obinutuzumab (OBI), and to evaluate immunological and clinical remission, adverse events, and quality of life. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Membranous Nephropathy - PLA2R Induced
- What is being tested?
- Obinutuzumab administration
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Oct 2025to 1 Apr 2028
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years.
- Diagnosis of PMN, confirmed by:
- Kidney biopsy or
- Positive serum PLA2Rab test either by IFT and/or ELISA)
- Serum PLA2Rab titer > 80 RU/ml
- Proteinuria ≥ 3.5 g/24h despite supportive treatment for at least 6 months with a maximally tolerated and stable dose of ACE-i or ARB.
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- Serum albumin < 30 g/l measured by BCP assay.
- eGFR ≥ 30 ml/min/1.73m2.
- Treatment with immunosuppression is warranted, as determined by the treating physician.
Who cannot join
- Secondary MN (e.g., hepatitis B or C infection, human immunodeficiency virus infection, active infection, systemic lupus erythematosus, sarcoidosis, IgG4-related, drug-induced, malignancy).
- RTX within 12 months prior to inclusion.
- CNI within 2 months prior to inclusion.
- Treatment with other immunosuppressive drugs within 6 months prior to inclusion.
- Proteinuria must not have decreased by > 50% over 6 months whilst taking ACEi/ARB.
- Life-threatening nephrotic syndrome resistant to treatment.
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- > 20% increase in serum creatinine not otherwise explained during antiproteinuric supportive treatment.
- Pregnancy or breastfeeding. Women of childbearing age and male patients with female partners of childbearing potential not willing to use contraception throughout the study and for at least 6 months after the last dose of obinutuzumab.
- Suspected or known hypersensitivity, allergy, and/or immunogenic reaction history to monoclonal antibodies, corticosteroid, cyclophosphamide, any of their ingredients, and any other drugs from these same pharmacotherapeutic groups.
- Known active infection of any kind or recent major episode of infection.
- Any disorder or condition which might pose an unacceptable risk to patient's safety and well-being that might interfere with completion of the study.
- Inability to understand or comply with the requirements of the study.
- Incapable of recognizing the nature, significance, and scope of the clinical trial or giving consent even with a legal representative.
- Use of an investigational agent.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Department of Nephrology, Radboud University Medical Center
Nijmegen
Ruben Visch, M.D., +31 (0)24 3092575, ruben.visch@radboudumc.nl
Anne-Els van de logt, M.D., PhD, anne-els.vandelogt@radboudumc.nl
About this study
Official title: Obinutuzumab Induced Decreases of PLA2Rab in MN: a Pilot Study
Objective: To assess the disappearance rate (half-life) of anti-PLA2R antibodies in high-risk primary membranous nephropathy (pMN) patients treated with obinutuzumab (OBI), and to evaluate immunological and clinical remission, adverse events, and quality of life.
Design: Open-label, single-center, prospective pilot intervention study conducted at Radboud University Medical Center.
Read more
Population: 20 adult patients with high-risk PMN, defined by proteinuria ≥3.5 g/24h despite 6 months of supportive treatment with ACE inhibitors or ARBs.
Intervention: OBI 1000 mg on days 1 and 15, with two additional infusions after 6 months if anti-PLA2R antibody levels remain positive and proteinuria exceeds 2 g/24h.
Follow-up: Patients were monitored at baseline, and at weeks 1, 2, 4, 8, 12, 24, 37, and 52.
Read the detailed description
Rationale:
Primary membranous nephropathy (PMN) is a leading cause of nephrotic syndrome in adults and is characterized by subepithelial immune complex deposits in the glomerular basement membrane. The disease is associated with circulating auto-antibodies targeting the M-type phospholipase A2 receptor (PLA2R), present in 70-80% of patients.
Despite advances in understanding its pathogenesis, the optimal treatment of PMN remains suboptimal; as the response to immunosuppressive therapy is often limited and slow. When considering treatment in PMN, the overall response rate is important, but in high-risk PMN patients the rapidity of response is even more important. As so, ideally we should be able to identify non-responders and slow-responders before or within a few months after start of therapy. A regimen consisting of rituximab (RTX), cyclophosphamide (CP) and steroids (triple therapy) has proven that a rapid immunological and clinical remission in PMN patients is possible. Obinutuzumab (OBI), a next-generation fully humanized anti-CD20 monoclonal antibody, offers enhanced B cell depletion through greater antibody-dependent cytotoxicity and reduced complement activation when compared to RTX. Retrospective studies suggests that OBI demonstrates superior efficacy in the treatment of treatment-refractory PMN patients compared to RTX, while maintaining a similar safety profile. It has been proven effective in the treatment of proliferative lupus nephritis compared to standard-of-care. These studies not only suggested better overall response, but the data also indicated a more rapid onset of remission.
Objective:
The primary objective of this pilot study is to calculate disappearance rate (half-life) of anti-PLA2R antibodies in PMN patients treated with OBI. We hypothesize that OBI monotherapy might be able to induce a rapid immunological response comparable to triple therapy in high-risk PLA2Rab-associated PMN patients. Secondary outcome measures are immunological remission, complete or partial clinical remission, adverse events and quality of life.
Main trial endpoint:
The main trial endpoint is the disappearance rate (half-life) of anti-PLA2R antibodies in PMN patients after treatment with OBI.
Secondary trial endpoints:
Immunological remission defined as IFT negative. Efficacy on clinical disease activity, defined as either CR or PR at 12 months. Adverse events. Quality of life during OBI treatment.
Trial design:
This is an open-label single-center, prospective, pilot intervention study in the Radboud UMC hospital. Patients at our outpatient clinic with high-risk PMN, defined by proteinuria ≥ 3.5 g/24h despite supportive treatment for at least 6 months with maximally tolerated and stable dose of ACE-i or ARB without life-threatening nephrotic syndrome and/or > 20% increase in serum creatinine not otherwise explained, that are eligible for inclusion will be asked to participate in the study. A total of 20 incident and prevalent PMN patients will be included. After informed consent participants will receive OBI 1000 mg on day 1 and 15, with two additional infusions after 6 months if the PLA2Rab IFT assay is still positive with proteinuria > 2 gram/24 hours and stable kidney function.
Patients will visit our outpatient clinic at baseline, in week 1, 2, 4, 8, 12, 24, 37 and 52. During the visits to our outpatient clinic, standard measurements will be performed, including blood pressure measurement, weight monitoring and laboratory testing, including PLA2Rab monitoring. Except for week 1, in which only PLA2Rab monitoring will be conducted. The "Kidney Disease Quality of Life-36" questionnaire will be completed at baseline and in week 12, 24, 37 and 52 prior to a visit to our outpatient clinic.
Trial population:
A total of 20 adult incident and prevalent anti-PLA2R antibody-associated high-risk PMN patients will be recruited from our renal unit.
Interventions:
All participants will receive OBI 1000 mg on day 1 and 15, with two additional infusions after 6 months if the anti-PLA2R antibody IFT assay is still positive with proteinuria > 2 gram/24 hours and stable kidney function. Anti-PLA2R antibodies will be measured at baseline and week 1, 2, 4, 8, 12, 24, 37 and 52.
- Conditions
- Membranous Nephropathy - PLA2R Induced
- Being tested
- Obinutuzumab administration
- Keywords
- PLA2R antibody kinetics, membranous nephropathy, obinutuzumab
- Medical subject headings
- Glomerulonephritis, Membranous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Obinutuzumab administrationDrug
All participants will receive obinutuzumab 1000 mg on day 1 and 15, with two additional infusions after 6 months if the anti-PLA2R antibody IFT assay is still positive with proteinuria > 2 gram/24 hours and stable kidney function.
| Study group | Role | What they receive |
|---|---|---|
| Treatment with obinutuzumab. | Experimental | Not described Receives: Drug: Obinutuzumab administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disappearance rate of PLA2R antibodies
To calculate the disappearance rate (half-life) of anti-PLA2R antibodies. Serum PLA2R antibodies will be measured at baseline, 1, 2, 4, 8, 12, 24 37 and 52 weeks after obinutuzumab infusions.
Measured: From baseline to 52 weeks after the first obinutuzumab infusion.
Secondary outcomes (4)
Immunological remission
Immunological remission, defined as negative accorording to the anti-PLA2R antibody immunofluorescence test (IFT).
Measured: From baseline to 52 weeks after the last obinutuzumab infusion.
Clinical efficacy
To assess efficacy of obinutuzumab on disease activity, defined as either complete remission (CR) or partial remission (PR).
Measured: From baseline to 52 weeks after the last obinutuzumab infusion.
Adverse events
To assess adverse events of treatment with obinutuzumab, categorized as SAE or NSAESI.
Measured: From baseline to 52 weeks after the last obinutuzumab infusion.
Quality of life during treatment
To determine quality of life (Kidney Disease Quality of Life-36) during obinutuzumab treatment.
Measured: From baseline to 52 weeks after the last obinutuzumab infusion.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2025
- Study start1 Oct 2025
- Primary completion1 Apr 2028 (estimated)
- Study completion1 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Membranous Nephropathy - PLA2R InducedStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Hoffmann-La Roche
- Responsible party
- Sponsor
- Investigators
- Anne-Els Van de Logt, M.D., PhD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07163611
- Sponsor's protocol ID
- 2025-521139-35-01
- Other IDs
- 2025-521139-35-01, 2025
- Status last verified
- Aug 2025
- First submitted
- 1 Sep 2025
- Last updated
- 6 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Obinutuzumab Induced Decreases of PLA2Rab in MN: a Pilot Study
- ClinicalTrials.gov ID
- NCT07163611
- Acronym / sponsor ID
- 2025-521139-35-01
- Conditions
- Membranous Nephropathy - PLA2R Induced
- Keywords
- PLA2R antibody kinetics, membranous nephropathy, obinutuzumab
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Hoffmann-La Roche
- Study start
- 1 Oct 2025 (actual)
- Primary completion
- 1 Apr 2028 (estimated)
- Study completion
- 1 Apr 2028 (estimated)
- First posted
- 9 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Objective: To assess the disappearance rate (half-life) of anti-PLA2R antibodies in high-risk primary membranous nephropathy (pMN) patients treated with obinutuzumab (OBI), and to evaluate immunological and clinical remission, adverse events, and quality of life.
Design: Open-label, single-center, prospective pilot intervention study conducted at Radboud University Medical Center.
Population: 20 adult patients with high-risk PMN, defined by proteinuria ≥3.5 g/24h despite 6 months of supportive treatment with ACE inhibitors or ARBs.
Intervention: OBI 1000 mg on days 1 and 15, with two additional infusions after 6 months if anti-PLA2R antibody levels remain positive and proteinuria exceeds 2 g/24h.
Follow-up: Patients were monitored at baseline, and at weeks 1, 2, 4, 8, 12, 24, 37, and 52.
Detailed description
Rationale:
Primary membranous nephropathy (PMN) is a leading cause of nephrotic syndrome in adults and is characterized by subepithelial immune complex deposits in the glomerular basement membrane. The disease is associated with circulating auto-antibodies targeting the M-type phospholipase A2 receptor (PLA2R), present in 70-80% of patients.
Despite advances in understanding its pathogenesis, the optimal treatment of PMN remains suboptimal; as the response to immunosuppressive therapy is often limited and slow. When considering treatment in PMN, the overall response rate is important, but in high-risk PMN patients the rapidity of response is even more important. As so, ideally we should be able to identify non-responders and slow-responders before or within a few months after start of therapy. A regimen consisting of rituximab (RTX), cyclophosphamide (CP) and steroids (triple therapy) has proven that a rapid immunological and clinical remission in PMN patients is possible. Obinutuzumab (OBI), a next-generation fully humanized anti-CD20 monoclonal antibody, offers enhanced B cell depletion through greater antibody-dependent cytotoxicity and reduced complement activation when compared to RTX. Retrospective studies suggests that OBI demonstrates superior efficacy in the treatment of treatment-refractory PMN patients compared to RTX, while maintaining a similar safety profile. It has been proven effective in the treatment of proliferative lupus nephritis compared to standard-of-care. These studies not only suggested better overall response, but the data also indicated a more rapid onset of remission.
Objective:
The primary objective of this pilot study is to calculate disappearance rate (half-life) of anti-PLA2R antibodies in PMN patients treated with OBI. We hypothesize that OBI monotherapy might be able to induce a rapid immunological response comparable to triple therapy in high-risk PLA2Rab-associated PMN patients. Secondary outcome measures are immunological remission, complete or partial clinical remission, adverse events and quality of life.
Main trial endpoint:
The main trial endpoint is the disappearance rate (half-life) of anti-PLA2R antibodies in PMN patients after treatment with OBI.
Secondary trial endpoints:
Immunological remission defined as IFT negative. Efficacy on clinical disease activity, defined as either CR or PR at 12 months. Adverse events. Quality of life during OBI treatment.
Trial design:
This is an open-label single-center, prospective, pilot intervention study in the Radboud UMC hospital. Patients at our outpatient clinic with high-risk PMN, defined by proteinuria ≥ 3.5 g/24h despite supportive treatment for at least 6 months with maximally tolerated and stable dose of ACE-i or ARB without life-threatening nephrotic syndrome and/or > 20% increase in serum creatinine not otherwise explained, that are eligible for inclusion will be asked to participate in the study. A total of 20 incident and prevalent PMN patients will be included. After informed consent participants will receive OBI 1000 mg on day 1 and 15, with two additional infusions after 6 months if the PLA2Rab IFT assay is still positive with proteinuria > 2 gram/24 hours and stable kidney function.
Patients will visit our outpatient clinic at baseline, in week 1, 2, 4, 8, 12, 24, 37 and 52. During the visits to our outpatient clinic, standard measurements will be performed, including blood pressure measurement, weight monitoring and laboratory testing, including PLA2Rab monitoring. Except for week 1, in which only PLA2Rab monitoring will be conducted. The "Kidney Disease Quality of Life-36" questionnaire will be completed at baseline and in week 12, 24, 37 and 52 prior to a visit to our outpatient clinic.
Trial population:
A total of 20 adult incident and prevalent anti-PLA2R antibody-associated high-risk PMN patients will be recruited from our renal unit.
Interventions:
All participants will receive OBI 1000 mg on day 1 and 15, with two additional infusions after 6 months if the anti-PLA2R antibody IFT assay is still positive with proteinuria > 2 gram/24 hours and stable kidney function. Anti-PLA2R antibodies will be measured at baseline and week 1, 2, 4, 8, 12, 24, 37 and 52.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment with obinutuzumab. | Experimental | Drug: Obinutuzumab administration |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age ≥ 18 years.
- Diagnosis of PMN, confirmed by:
- Serum PLA2Rab titer > 80 RU/ml
- Proteinuria ≥ 3.5 g/24h despite supportive treatment for at least 6 months with a maximally tolerated and stable dose of ACE-i or ARB.
- Serum albumin < 30 g/l measured by BCP assay.
Key exclusion criteria (14 listed)
- Secondary MN (e.g., hepatitis B or C infection, human immunodeficiency virus infection, active infection, systemic lupus erythematosus, sarcoidosis, IgG4-related, drug-induced, malignancy).
- RTX within 12 months prior to inclusion.
- CNI within 2 months prior to inclusion.
- Treatment with other immunosuppressive drugs within 6 months prior to inclusion.
- Proteinuria must not have decreased by > 50% over 6 months whilst taking ACEi/ARB.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Obinutuzumab administrationAll participants will receive obinutuzumab 1000 mg on day 1 and 15, with two additional infusions after 6 months if the anti-PLA2R antibody IFT assay is still positive with proteinuria > 2 gram/24 hours and stable kidney function. | Drug | Treatment with obinutuzumab. |
Primary outcome
Disappearance rate of PLA2R antibodies
Time frame: From baseline to 52 weeks after the first obinutuzumab infusion.
To calculate the disappearance rate (half-life) of anti-PLA2R antibodies. Serum PLA2R antibodies will be measured at baseline, 1, 2, 4, 8, 12, 24 37 and 52 weeks after obinutuzumab infusions.
4 secondary outcomes
Immunological remission
Time frame: From baseline to 52 weeks after the last obinutuzumab infusion.
Clinical efficacy
Time frame: From baseline to 52 weeks after the last obinutuzumab infusion.
Adverse events
Time frame: From baseline to 52 weeks after the last obinutuzumab infusion.
Quality of life during treatment
Time frame: From baseline to 52 weeks after the last obinutuzumab infusion.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Anne-Els Van de Logt, M.D., PhD principal investigator
Radboud University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Obinutuzumab administration in people with Membranous Nephropathy - PLA2R Induced, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ruben Visch, M.D. (+31 (0)24 3092575, ruben.visch@radboudumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disappearance rate of PLA2R antibodies (time frame: From baseline to 52 weeks after the first obinutuzumab infusion.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2026.