Clinical trial NCT01093157: A Dose Escalation Study of Long-acting ACTH Gel in Membranous Nephropathy
Official title: A Dose-finding Pilot Study of ACTH (Adrenocorticotropic Hormone) on the Proteinuria and Serum Lipoprotein Profile in Patients With Idiopathic Membranous Nephropathy (MN)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Glomerulonephritis
Keywords: Kidney disease, Glomerulonephritis
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: Mallinckrodt
First posted: 2010-03-25
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 72
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Membranous Nephropathy (MN) is an immune-mediated kidney disease that affects the glomerulus or the filter that removes toxins from the blood. Damage to the membrane that separates blood from urine results in loss of protein into the urine (proteinuria) and in some cases loss of kidney function.There is no standard specific treatment for MN.

ACTH has a pronounced lipid-lowering effect in healthy individuals, in steroid-treated patients with renal disease and in hemodialysis patients Some studies suggest that prolonged synthetic ACTH therapy may represent an effective therapy in patients with idiopathic MN, more extensive randomized studies with longer follow-up are needed before therapeutic recommendations can be made.

We propose to do a pilot study to test the hypothesis that biologic ACTH, a slow-release formulation of corticotropin extracted from porcine pituitary glands (H.P. Acthar gel) will be effective in reducing proteinuria and improving lipid profile in patients with idiopathic MN.


Eligibility criteria: Inclusion Criteria:• Idiopathic MN with diagnostic biopsy performed less than 36 months from the time of dose randomization.

* 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 (BP \<130/75 mm Hg in \>75% of the readings). Patients with documented evidence of \>3 months treatment with maximal Ang II blockade, target BP (BP \<130/75 mm Hg in \>75% of the readings) and who remain with proteinuria \>4.0g/24h may enter the ACTH phase of the study without the need to have the run-in/conservative phase of the study.
* Proteinuria as measured by Uprot/Ucr \> 4.0 on a spot sample aliquot from a 24-hour urine collection. The choice of Uprot/UCr is in accord with recent NKF-CKD guidelines.\[9\]
* Estimated GFR ≥ 40 ml/min/1.73m2 while taking ACEI/ARB therapy. The GFR will be estimated using the 4 variable MDRD equation as published in the NKF-CKD guidelines.\[9\] The same NKF-CKD guidelines also promote the use of estimated GFR (GFRest) values rather than serum creatinine levels or CrCl measurements as the preferred non-invasive method of determining glomerular filtration rates.\[9\]

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 (e.g. hepatitis B, SLE, medications, malignancies). Testing for HIV, Hepatitis B and C should have occurred \< 2 years prior to enrollment into the study.
* Type 1 or 2 diabetes mellitus: to exclude proteinuria secondary to diabetic nephropathy. Patients who have recent history of steroid induced diabetes but no evidence on renal biopsy performed within 6 months of entry into the study are eligible for enrollment.
* Pregnancy or nursing - for safety reasons.
* Acute renal vein thrombosis documented prior to entry by renal US or CT scan and requiring anticoagulation therapy.

Primary outcomes:
measure: change in proteinuria from baseline to value at 3 months .
timeFrame: 3 months
Secondary outcomes:
measure: Complete Remission(CR) or Partial Remission (PR) at 3 months
timeFrame: 3 months
measure: Adverse effects
timeFrame: Throughout three months of this study and for nine months follow-up
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: University Health Network- Toronto General Hospital
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Daniel Cattran, M.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.