Adrenocorticotropic Hormone in Membranous Nephropathy

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

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.

Study Overview

• Status: Completed
• Conditions: Membranous Nephropathy
• Intervention / Treatment: Drug: ACTHar

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Acthar; Acthar will be administered subcutaneously (SC) 80 units for the first week and then 80 units twice weekly	Drug: ACTHar; for 6 months; Other Names: ACTH; Repository corticotropin injection; Acthar Injectable Product; RCI; Acthar® Gel

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Investigators: Principal Investigator: Paolo Cravedi, MD, PhD, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 19, 2018
• Primary Completion (ACTUAL): December 16, 2020
• Study Completion (ACTUAL): December 16, 2020

Study Registration Dates

• First Submitted: January 17, 2017
• First Submitted That Met QC Criteria: January 17, 2017
• First Posted (ESTIMATE): January 20, 2017

Study Record Updates

• Last Update Posted (ACTUAL): August 15, 2022
• Last Update Submitted That Met QC Criteria: July 20, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: proteinuria; glomerulonephritis; ACTH; adrenocorticotropic hormone; Membranous nephropathy
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Kidney Diseases; Glomerulonephritis, Membranous; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenocorticotropic Hormone
• Other Study ID Numbers: GCO 16-2402

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: Yes
• Studies a U.S. FDA-regulated device product: No