Dose-Finding Pilot Study of ACTH in Patients With Idiopathic Membranous Nephropathy

Study Overview
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Brief Summary
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This pilot study is aimed at demonstrating the effectiveness of ACTH (H.P. Acthar Gel) on the lipid profile and proteinuria in participants with MN. ACTH or adrenocorticotrophin is a hormone produced by the pituitary gland (a gland at the base of your brain) that is involved in stimulating your adrenal glands to secrete a number of steroid products (e.g. cortisol, aldosterone, corticosterone, and others) that are important in keeping you alive. The drug used in this study has been approved by the Food and Drug Administration (FDA) for routine clinical use in the treatment of patients with proteinuria and patients with idiopathic nephrotic syndrome such as idiopathic MN. However, the most adequate dose to use has not been adequately assessed. This is the reason for conducting this research study.

Official Title
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A Dose-Finding Pilot Study of ACTH on the Serum Lipoprotein Profile and Proteinuria in Patients With Idiopathic Membranous Nephropathy (MN)

Conditions
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Idiopathic Membranous Nephropathy

Intervention / Treatment
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* Drug: ACTH


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Idiopathic MN with diagnostic biopsy performed less than 36 months from the time of dose randomization. Age > 18 years. Patients need to be treated with an ACEI and/or ARB, for at least 3 months prior to ACTH treatment and have adequately controlled blood pressure Proteinuria of >4.0 on a 24-hour urine collection. Estimated GFR >40 ml/min/1.73m2 while taking ACEI/ARB therapy. Exclusion Criteria: Age <18 years. Estimated GFR <40 ml/min/1.73m2, or serum creatinine >2.0 mg/dl. Renal biopsy showing more than 30% glomerulosclerosis and/or tubular atrophy. Patient must be off glucocorticoid, calcineurin inhibitors (cyclosporin A, tacrolimus) or mycophenolic mofetil for >1 month, and alkylating agents or rituximab for >6 months. Resistance to the following immunosuppressive routines e.g. steroids alone, calcineurin inhibitors plus or minus steroids, cytotoxic agents plus or minus steroids. Patients with active infections or secondary causes of MN. Type 1 or 2 diabetes mellitus. Pregnancy or nursing. Acute renal vein thrombosis documented prior to entry by renal US or CT scan and requiring anticoagulation therapy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1 ACTH 40 units<br>Receive ACTH at the dose of 40 units sub-cutaneously for up to 12 weeks. If at day 91 no response has been shown, you will have the option to increase the dose of ACTH to 80 units for up to an additional 120 days. | Drug: ACTH<br>* comparison of different dosages of drug<br>* Other names: H.P. Acthar Gel;|
| Active Comparator: Arm 2 ACTH 80 units<br>Receive ACTH at the dose of 80 units sub-cutaneously for up to 12 weeks. | Drug: ACTH<br>* comparison of different dosages of drug<br>* Other names: H.P. Acthar Gel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in proteinuria |  | baseline, 3 months | 
| Change in LDL cholesterol, HDL cholesterol, and triglycerides |  | baseline, 3 months | 
| Change in side effects/toxicity |  | baseline, 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with CR or PR |  | 3 months | 
| The effect of maximizing angiotensin II blockade on proteinuria |  | 3 months |