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

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

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.

Study Overview

• Status: Completed
• Conditions: Idiopathic Membranous Nephropathy
• Intervention / Treatment: Drug: ACTH

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5R 0A3
      • University of Toronto
• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Idiopathic MN with diagnostic biopsy performed less than 36 months from the time of dose randomization.
2. Age > 18 years.
3. 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
4. Proteinuria of >4.0 on a 24-hour urine collection.
5. Estimated GFR >40 ml/min/1.73m2 while taking ACEI/ARB therapy.

Exclusion Criteria:

1. Age <18 years.
2. Estimated GFR <40 ml/min/1.73m2, or serum creatinine >2.0 mg/dl.
3. Renal biopsy showing more than 30% glomerulosclerosis and/or tubular atrophy.
4. Patient must be off glucocorticoid, calcineurin inhibitors (cyclosporin A, tacrolimus) or mycophenolic mofetil for >1 month, and alkylating agents or rituximab for >6 months.
5. Resistance to the following immunosuppressive routines e.g. steroids alone, calcineurin inhibitors plus or minus steroids, cytotoxic agents plus or minus steroids.
6. Patients with active infections or secondary causes of MN.
7. Type 1 or 2 diabetes mellitus.
8. Pregnancy or nursing.
9. Acute renal vein thrombosis documented prior to entry by renal US or CT scan and requiring anticoagulation therapy.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1 ACTH 40 units; 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; comparison of different dosages of drug; Other Names: H.P. Acthar Gel
Active Comparator: Arm 2 ACTH 80 units; Receive ACTH at the dose of 80 units sub-cutaneously for up to 12 weeks.	Drug: ACTH; comparison of different dosages of drug; Other Names: H.P. Acthar Gel

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: Mallinckrodt
• Investigators: Principal Investigator: Fernando C Fervenza, M.D., Ph.D, Mayo Clinic

Publications and helpful links

General Publications

• von Groote TC, Williams G, Au EH, Chen Y, Mathew AT, Hodson EM, Tunnicliffe DJ. Immunosuppressive treatment for primary membranous nephropathy in adults with nephrotic syndrome. Cochrane Database Syst Rev. 2021 Nov 15;11(11):CD004293. doi: 10.1002/14651858.CD004293.pub4.

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: December 9, 2008
• First Submitted That Met QC Criteria: December 9, 2008
• First Posted (Estimate): December 10, 2008

Study Record Updates

• Last Update Posted (Estimate): October 13, 2014
• Last Update Submitted That Met QC Criteria: October 10, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Kidney Diseases; Glomerulonephritis, Membranous
• Other Study ID Numbers: 08-006328