Membranous Nephropathy
Conditions
Keywords
Membranous nephropathy, adrenocorticotropic hormone, ACTH, proteinuria, glomerulonephritis
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.
Interventions
DRUGACTHar
for 6 months
Sponsors
Icahn School of Medicine at Mount Sinai
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Change in Serum Albumin | baseline 6 months, 12 months | Change in serum albumin from baseline |
| Anti-PLA2R Antibodies Levels | 12 months | blood levels Number of anti-PLA2R memory B cells |
| Number of Anti-PLA2R Memory B Cells | 12 months | 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 |
| Estimated Glomerular Filtration Rate (GFR) | baseline and 12 months | GFR measures kidney function. |
Countries
United States
Participant flow
Recruitment details
Enrollment from March 2018 and June 2019
Participants by arm
| Arm | Count |
|---|---|
| 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. | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Acthar | — |
|---|---|---|
| Age, Continuous | 53.75 years STANDARD_DEVIATION 8.098 | — |
| Negative for Anti-PLA2R Ab | 4 Participants | — |
| Number of Participants with previous treatment | 2 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Serum albumin | 3 g/dL STANDARD_DEVIATION 1.01 | — |
| Serum creatine | 0.965 mg/dL STANDARD_DEVIATION 0.118 | — |
| Sex: Female, Male Female | 0 Participants | — |
| Sex: Female, Male Male | 4 Participants | — |
| Urine protein/creatinine ratio (P/C) | 6.173 g/g STANDARD_DEVIATION 3.545 | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 0 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
Change in Proteinuria
Change in proteinuria at baseline versus after 12 months of treatment as measured by urine protein/creatinine ratio
Time frame: baseline and 12 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Acthar | Change in Proteinuria | baseline | 4.56 ratio |
| Acthar | Change in Proteinuria | 12 months | 1.36 ratio |
Secondary
Anti-PLA2R Antibodies Levels
blood levels Number of anti-PLA2R memory B cells
Time frame: 12 months
Population: Data not collected
Secondary
Change in CD4+CD25+CD127low T Regulatory Cells/CD4+ T Cell Ratio
blood levels - one single cell subset identified by different markers
Time frame: baseline and 12 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Acthar | Change in CD4+CD25+CD127low T Regulatory Cells/CD4+ T Cell Ratio | 12 Months | 0.12 ratio |
| Acthar | Change in CD4+CD25+CD127low T Regulatory Cells/CD4+ T Cell Ratio | Baseline | 0.04 ratio |
Secondary
Change in Serum Albumin
Change in serum albumin from baseline
Time frame: baseline 6 months, 12 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Acthar | Change in Serum Albumin | baseline and 6 months | 3.0 g/dl |
| Acthar | Change in Serum Albumin | baseline and 12 months | 3.65 g/dl |
Secondary
Estimated Glomerular Filtration Rate (GFR)
GFR measures kidney function.
Time frame: baseline and 12 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Acthar | Estimated Glomerular Filtration Rate (GFR) | baseline | 90.5 mL/min |
| Acthar | Estimated Glomerular Filtration Rate (GFR) | 12 months | 80.5 mL/min |
Secondary
Number of Anti-PLA2R Memory B Cells
Number of anti-PLA2R memory B cells
Time frame: 12 months
Population: Data not collected
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.
Time frame: 12 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Acthar | Number of Participants With Complete or Partial Remission | complete remission | 0 Participants |
| Acthar | Number of Participants With Complete or Partial Remission | partial remission | 4 Participants |