A Dose Escalation Study of Long-acting ACTH Gel in Membranous Nephropathy

Recruitment & Eligibility

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.

Study & Design

Arm && Interventions

Group	Intervention	Description
ACTH (HP Acthar gel) 40 units	Adrenocorticotrophic hormone ACTH	-
ACTH (HP Acthar gel) 80 units	Adrenocorticotrophic hormone ACTH	-

Primary Outcome Measures

Name	Time	Method
change in proteinuria from baseline to value at 3 months .	3 months

Secondary Outcome Measures

Name	Time	Method
Complete Remission(CR) or Partial Remission (PR) at 3 months	3 months	Definition of proteinuric status. UP = urinary protein (g/24h) Complete remission (CR) UP ≤ 0.3 g Partial remission (PR) Reduction in UP of \> 50% plus final UP ≤ 3.5 g but \>0.3g Non-response (NR) Reduction in UP of \< 50%. (includes increase in UP \<50%) Progression Proteinuria increases by \> 50%
Adverse effects	Throughout three months of this study and for nine months follow-up	Patients will be directly questioned every two weeks during the drug exposure and then at monthly intervals during follow-up. In addition a contact number will be provided to the subjects to call if they experience any adverse affect or if they suspect adverse effect at any time between specific visits

Recruitment & Eligibility