Early PLA2R Status in Severe Anti-PLA2R-mediated Membranous Nephropathy and Long Term Kidney Outcome. (EPSILON)

November 5, 2026 updated by: Assistance Publique - Hôpitaux de Paris

This is a multicentric retrospective observational cohort study. The aim of this study is to evaluate, during the initial phase of immunosuppressive treatment for severe PLA2R-positive membranous nephropathy, the independent association between anti-PLA2R antibody trajectories and the occurrence of long-term major kidney events (within 10 years after treatment initiation).

The secondary objectives are :

To assess the association between the initial anti-PLA2R antibody trajectory (between 0 and 6 ± 3 months after treatment, before any potential re-treatment) and the occurrence of nephrological remission.

To assess the association between the initial anti-PLA2R antibody trajectory (between 0 and 6 ± 3 months after treatment, before any potential re-treatment) and the occurrence of immunological remission.

To evaluate, in real-world practice, the safety of immunosuppressive therapies in the treatment of severe PLA2R-positive membranous nephropathy.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

Membranous nephropathy (MN) is the leading cause of nephrotic syndrome in non-diabetic Caucasian adults, with a highly variable disease course. One-third of patients achieve spontaneous remission, one-third develop chronic kidney disease, and another third progress to end-stage renal disease (ESRD). This variability necessitates early risk assessment to prevent both overtreatment and disease progression.

Anti-PLA2R antibodies, detected in 60-65% of cases, are crucial for diagnosis and disease monitoring. High antibody levels are associated with a low likelihood of spontaneous remission, often justifying early immunosuppressive therapy. However, the precise predictive value and threshold levels of these antibodies remain unclear.

Among available immunosuppressive treatments, rituximab is favored for its efficacy and low toxicity, making it the standard therapy for MN. However, only 30-35% of patients achieve complete remission within two years, while two-thirds of those without complete remission remain at risk of progression to ESRD.

This variability in response to rituximab is likely influenced by several factors, including excessive urinary drug loss, immune resistance, genetic predispositions, and comorbidities such as obesity and vitamin D deficiency. Although personalized therapeutic approaches are under investigation, large-scale validation is needed.

In conclusion, despite significant advancements, particularly with anti-PLA2R antibodies and rituximab, multicenter studies are required to refine therapeutic strategies and improve long-term outcomes in anti-PLA2R+ MN by promoting a more personalized approach to treatment.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
250

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

6 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients with antiPLA2R positive membranous nephropathy will be obtained from the immunology laboratories of Saint Antoine Hospital and Mondor Hospital (performing all antiPLA2R analysis in Paris).

Description

Inclusion Criteria:

  • Patient followed in 8 nephrology departments of AP-HP between 01/01/2017 and 12/31/2026
  • Age > 6 years
  • With serodiagnosis of MN via identification of anti-PLA2R antibodies
  • Treatment with an immunosuppressive drug.

Exclusion Criteria:

  • Diagnosis of MN without testing for anti-PLA2R antibodies
  • Refusal to use the data
  • Occurrence of the primary endpoint at the time of disease diagnosis (diagnosis of membranous nephropathy at the stage of end-stage kidney disease)
  • Lack of patient follow-up at the centers participating in the study
  • Lack of reassessment of anti-PLA2R antibody titers within 12 months after initiation of immunosuppressive therapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: COHORT
  • Time Perspectives: RETROSPECTIVE

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Occurrence of a major nephrological event within 10 years following immunosuppressive treatment for anti-PLA2R-positive membranous nephropathy
Time Frame: between diagnostic and last follow-up, up to 10 years

Major adverse kidney event (MAKE) - Composite variable defined by one of the following event:

  • Initiation of chronic dialysis (duration > 3 months).
  • Kidney transplantation.
  • Chronic kidney disease with a sustained estimated GFR < 15 ml/min/1.73m², confirmed by two measurements at least 28 days apart.
  • Sustained decline of > 50% in GFR from baseline at diagnosis, confirmed by two measurements at least 28 days apart.
between diagnostic and last follow-up, up to 10 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Association between the initial trajectory (defined as the percentage change ((M6 - M0)/M0) in the anti-PLA2R antibody titer
Time Frame: between diagnostic and last follow-up, , up to 10 years

Association between the initial trajectory (defined as the percentage change ((M6 - M0)/M0) in the anti-PLA2R antibody titer, quantified using the ELISA technique, between the titer at the time of initiation of immunosuppressive therapy (D0) and the titer from the first anti-PLA2R measurement performed at 6 ± 3 months after initiation of immunosuppressive therapy (M6 ± 3)) of anti-PLA2R antibodies (from 0 to 6+/-3 months post-treatment) and the occurrence of nephrological response (either complete and/or partial).

Nephrological relapse is defined as :

  • The occurrence of proteinuria >3 g/g in a patient who had previously achieved complete or partial remission.
  • The occurrence of a clinically significant relapse, defined as a relapse warranting immunosuppressive therapy in any of specifics situations
between diagnostic and last follow-up, , up to 10 years
Association between the initial trajectory of anti-PLA2R antibodies (from 0 to 6 +/- 3 months post-treatment) and the occurrence of immune response
Time Frame: between diagnostic and last follow-up, , up to 10 years

Immunological relapse is defined as reappearance of detectable anti-PLA2R antibodies by ELISA after achieving anti-PLA2R antibody negativity during treatment.
between diagnostic and last follow-up, , up to 10 years
Safety of immunosuppressive drugs
Time Frame: between diagnostic and last follow-up, , up to 10 years

Reporting of all adverse event recorded in patients' medical record during follow up. Scoring performed according to the CTCAE v5.0.
between diagnostic and last follow-up, , up to 10 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Assistance Publique - Hôpitaux de Paris

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Romain BROUSSE, MD, PhD student, Assistance Publique - Hôpitaux de Paris

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 5, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 5, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 12, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 12, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 5, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • APHP251555

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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