Adrenocorticotropic Hormone in Membranous Nephropathy
Primary Purpose
Membranous Nephropathy
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
ACTHar
Sponsored by
About this trial
This is an interventional treatment trial for Membranous Nephropathy focused on measuring Membranous nephropathy, adrenocorticotropic hormone, ACTH, proteinuria, glomerulonephritis
Eligibility Criteria
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
Sites / Locations
- Icahn School of Medicine at Mount Sinai
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Acthar
Arm Description
Acthar will be administered subcutaneously (SC) 80 units for the first week and then 80 units twice weekly
Outcomes
Primary Outcome Measures
Change in Proteinuria
Change in proteinuria at baseline versus after 12 months of treatment as measured by urine protein/creatinine ratio
Secondary Outcome Measures
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.
Change in Serum Albumin
Change in serum albumin from baseline
Estimated Glomerular Filtration Rate (GFR)
GFR measures kidney function.
Number of Anti-PLA2R Memory B Cells
Number of anti-PLA2R memory B cells
Anti-PLA2R Antibodies Levels
blood levels
Number of anti-PLA2R memory B cells
Change in CD4+CD25+CD127low T Regulatory Cells/CD4+ T Cell Ratio
blood levels - one single cell subset identified by different markers
Full Information
NCT ID
NCT03025828
First Posted
January 17, 2017
Last Updated
July 20, 2022
Sponsor
Icahn School of Medicine at Mount Sinai
1. Study Identification
Unique Protocol Identification Number
NCT03025828
Brief Title
Adrenocorticotropic Hormone in Membranous Nephropathy
Official Title
Changes in Autoreactive Memory B Cells as Biomarker of Response to Adrenocorticotropic Hormone in Patients With Membranous Nephropathy
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
March 19, 2018 (Actual)
Primary Completion Date
December 16, 2020 (Actual)
Study Completion Date
December 16, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Icahn School of Medicine at Mount Sinai
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Membranous Nephropathy
Keywords
Membranous nephropathy, adrenocorticotropic hormone, ACTH, proteinuria, glomerulonephritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Acthar
Arm Type
Experimental
Arm Description
Acthar will be administered subcutaneously (SC) 80 units for the first week and then 80 units twice weekly
Intervention Type
Drug
Intervention Name(s)
ACTHar
Other Intervention Name(s)
ACTH, Acthar Injectable Product, Repository corticotropin injection, RCI, Acthar® Gel
Intervention Description
for 6 months
Primary Outcome Measure Information:
Title
Change in Proteinuria
Description
Change in proteinuria at baseline versus after 12 months of treatment as measured by urine protein/creatinine ratio
Time Frame
baseline and 12 months
Secondary Outcome Measure Information:
Title
Number of Participants With Complete or Partial Remission
Description
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.
Time Frame
12 months
Title
Change in Serum Albumin
Description
Change in serum albumin from baseline
Time Frame
baseline 6 months, 12 months
Title
Estimated Glomerular Filtration Rate (GFR)
Description
GFR measures kidney function.
Time Frame
baseline and 12 months
Title
Number of Anti-PLA2R Memory B Cells
Description
Number of anti-PLA2R memory B cells
Time Frame
12 months
Title
Anti-PLA2R Antibodies Levels
Description
blood levels
Number of anti-PLA2R memory B cells
Time Frame
12 months
Title
Change in CD4+CD25+CD127low T Regulatory Cells/CD4+ T Cell Ratio
Description
blood levels - one single cell subset identified by different markers
Time Frame
baseline and 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paolo Cravedi, MD, PhD
Organizational Affiliation
Icahn School of Medicine at Mount Sinai
Official's Role
Principal Investigator
Facility Information:
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Adrenocorticotropic Hormone in Membranous Nephropathy
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