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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Acthar | Experimental | Acthar will be administered subcutaneously (SC) 80 units for the first week and then 80 units twice weekly |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ACTHar | Drug | for 6 months |
|
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Paolo Cravedi, MD, PhD | Icahn School of Medicine at Mount Sinai | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Icahn School of Medicine at Mount Sinai | New York | New York | 10029 | United States |
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Enrollment from March 2018 and June 2019
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| ID | Title | Description |
|---|---|---|
| FG000 | Acthar | Acthar will be administered subcutaneously (SC) 80 units for the first week and then 80 units twice weekly for 6 months |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Acthar | Acthar administered subcutaneously (SC) 80 units for the first week and then 80 units twice weekly for 6 months of treatment with a cumulative dose exposure of 3,920 units. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Proteinuria | Change in proteinuria at baseline versus after 12 months of treatment as measured by urine protein/creatinine ratio | Posted | Median | Inter-Quartile Range | ratio | baseline and 12 months |
|
|
12 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Acthar | Acthar administered subcutaneously (SC) 80 units for the first week and then 80 units twice weekly for 6 months of treatment with a cumulative dose exposure of 3,920 units. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Kirk Campbell | Icahn School of Medicine at Mount Sinai | 212-241-6271 | kirk.campbell@mssm.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 16, 2018 | Jul 13, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D015433 | Glomerulonephritis, Membranous |
| D011507 | Proteinuria |
| D005921 | Glomerulonephritis |
| ID | Term |
|---|---|
| D009393 | Nephritis |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
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| ID | Term |
|---|---|
| D000324 | Adrenocorticotropic Hormone |
| ID | Term |
|---|---|
| D053486 | Melanocortins |
| D011333 | Pro-Opiomelanocortin |
| D007028 | Hypothalamic Hormones |
| D036361 | Peptide Hormones |
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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 |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Serum albumin | Mean | Standard Deviation | g/dL |
|
| Serum creatine | Mean | Standard Deviation | mg/dL |
|
| Negative for Anti-PLA2R Ab | Threshold for anti-PLA2R Ab positivity is 19.9 RU/mL. | Count of Participants | Participants |
|
| Urine protein/creatinine ratio (P/C) | Mean | Standard Deviation | g/g |
|
| Number of Participants with previous treatment | Participants who had previously received treatment with steroids, alkylating agents, calcineurin inhibitors, and/or rituximab. | Count of Participants | Participants |
|
|
| Secondary | 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. | Posted | Count of Participants | Participants | 12 months |
|
|
|
| Secondary | Change in Serum Albumin | Change in serum albumin from baseline | Posted | Median | Inter-Quartile Range | g/dl | baseline 6 months, 12 months |
|
|
|
| Secondary | Estimated Glomerular Filtration Rate (GFR) | GFR measures kidney function. | Posted | Median | Inter-Quartile Range | mL/min | baseline and 12 months |
|
|
|
| Secondary | Number of Anti-PLA2R Memory B Cells | Number of anti-PLA2R memory B cells | Data not collected | Posted | 12 months |
|
|
| Secondary | Anti-PLA2R Antibodies Levels | blood levels Number of anti-PLA2R memory B cells | Data not collected | Posted | 12 months |
|
|
| Secondary | Change in CD4+CD25+CD127low T Regulatory Cells/CD4+ T Cell Ratio | blood levels - one single cell subset identified by different markers | Posted | Median | Inter-Quartile Range | ratio | baseline and 12 months |
|
|
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| 0 |
| 4 |
| 0 |
| 4 |
| 0 |
| 4 |
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| D005261 |
| Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D014555 | Urination Disorders |
| D020924 | Urological Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006728 |
| Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010908 | Pituitary Hormones, Anterior |
| D010907 | Pituitary Hormones |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |