Adrenocorticotropic Hormone in Membranous Nephropathy

Phase 4

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

Inclusion Criteria

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

Arm && Interventions

Group	Intervention	Description
Acthar	ACTHar	Acthar will be administered subcutaneously (SC) 80 units for the first week and then 80 units twice weekly

Primary Outcome Measures

Name	Time	Method
Change in Proteinuria	baseline and 12 months	Change in proteinuria at baseline versus after 12 months of treatment as measured by urine protein/creatinine ratio

Secondary Outcome Measures

Name	Time	Method
Estimated Glomerular Filtration Rate (GFR)	baseline and 12 months	GFR measures kidney function.
Change in Serum Albumin	baseline 6 months, 12 months	Change in serum albumin from baseline
Number of Participants With Complete or Partial Remission	12 months	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.
Anti-PLA2R Antibodies Levels	12 months	blood levels Number of anti-PLA2R memory B cells
Change in CD4+CD25+CD127low T Regulatory Cells/CD4+ T Cell Ratio	baseline and 12 months	blood levels - one single cell subset identified by different markers
Number of Anti-PLA2R Memory B Cells	12 months	Number of anti-PLA2R memory B cells