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

NCT00805753 | Completed Phase 1 DMC

• 1 other identifier: 08-006328
• Study Type: interventional
• Target: 20
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

Idiopathic Membranous Nephropathy

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (2)

• Number of subjects with CR or PR

  3 months

• The effect of maximizing angiotensin II blockade on proteinuria

  3 months

Study Arms (2)

Arm 1 ACTH 40 units

ACTIVE COMPARATOR

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

Arm 2 ACTH 80 units

ACTIVE COMPARATOR

Receive ACTH at the dose of 80 units sub-cutaneously for up to 12 weeks.

Drug: ACTH

Interventions

ACTH DRUG

comparison of different dosages of drug

Also known as: H.P. Acthar Gel

Arm 1 ACTH 40 units; Arm 2 ACTH 80 units

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mayo Clinic: lead
• Mallinckrodt: collaborator

Study Sites (2)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University of Toronto

Toronto, Ontario, M5R 0A3, Canada

Location

Related Publications (1)

• 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.

  PMID: 34778952 DERIVED

MeSH Terms

Conditions

Glomerulonephritis, Membranous

Interventions

Adrenocorticotropic Hormone

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Melanocortins; Pro-Opiomelanocortin; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormones, Anterior; Pituitary Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins

Study Officials

• Fernando C Fervenza, M.D., Ph.D

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D., Ph.D.

Study Record Dates

• First Submitted: December 9, 2008
• First Posted: December 10, 2008
• Study Start: January 1, 2009
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2014
• Last Updated: October 13, 2014

Record last verified: 2014-10

Locations

US (1); CA (1)