Adrenocorticotropic Hormone in Membranous Nephropathy

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of adrenocorticotropic hormone (ACTH, Acthar) on the loss of proteins in the urine (proteinuria) in patients with membranous nephropathy. Acthar is a hormone that stimulates steroid production from small glands above the kidneys. It has direct protective effects on the kidney and is currently approved by the FDA to treat kidney disorders associated with proteins in the urine, but the mechanisms of action are not entirely understood and will be studied in the present trial.

Detailed Description
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Patients with membranous nephropathy and nephrotic syndrome will be treated with ACTH for 6 months. Proteinuria remission at 12 months will be the primary endpoint. Different biomarkers including anti-PLA2R autoantibodies, circulating regulatory T cells, and autoreactive memory B cells will be serially measured to identify predictors of response to therapy.

Official Title
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Changes in Autoreactive Memory B Cells as Biomarker of Response to Adrenocorticotropic Hormone in Patients With Membranous Nephropathy

Conditions
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Membranous Nephropathy

Intervention / Treatment
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* Drug: ACTHar


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 to 70 years Free of immunosuppression for at least 3 months Capability of understanding the purpose of the study Written informed consent Exclusion Criteria: Epidermal growth factor receptor (eGFR) < 30ml/min/1.73m2 Kidney Transplant Secondary MN (defined on the basis of clinical criteria) Type 1 or Type 2 diabetes mellitus (prior diagnosis of gestational diabetes mellitus is not an exclusion) History of previous use of Acthar for treatment of nephrotic syndrome Prior sensitivity to Acthar or other porcine protein products Contraindication to Acthar per Prescribing Information Planned treatment with live or live attenuated vaccines once enrolled in the study More than three previous treatment regiments Participation to other clinical trials over the previous 12 months History of cancer, except carcinoma in situ and treated basal and squamous cell carcinomas Pregnancy Lactation Current substance abuse Any clinically relevant condition that might affect study participation and/or study results

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acthar<br>Acthar will be administered subcutaneously (SC) 80 units for the first week and then 80 units twice weekly | Drug: ACTHar<br>* for 6 months<br>* Other names: Acthar® Gel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Proteinuria | Change in proteinuria at baseline versus after 12 months of treatment as measured by urine protein/creatinine ratio | baseline and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Complete or Partial Remission | Complete (proteinuria reduction <500mg/24h) or partial (urinary protein excretion (P/C) <3.0 g/g (with at least 50% reduction versus baseline) in at least two consecutive visits) remission. | 12 months | 
| Change in Serum Albumin | Change in serum albumin from baseline | baseline 6 months, 12 months | 
| Estimated Glomerular Filtration Rate (GFR) | GFR measures kidney function. | baseline and 12 months | 
| Number of Anti-PLA2R Memory B Cells | Number of anti-PLA2R memory B cells | 12 months | 
| Anti-PLA2R Antibodies Levels | blood levels Number of anti-PLA2R memory B cells | 12 months | 
| Change in CD4+CD25+CD127low T Regulatory Cells/CD4+ T Cell Ratio | blood levels - one single cell subset identified by different markers | baseline and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Membranous nephropathy, adrenocorticotropic hormone, ACTH, proteinuria, glomerulonephritis