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

Purpose

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.

Condition	Intervention	Phase
Glomerulonephritis	Drug: Adrenocorticotrophic hormone ACTH	Phase 1 Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
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)

Resource links provided by NLM:

MedlinePlus related topics: Hormones Kidney Diseases

Drug Information available for: Corticotropin

Genetic and Rare Diseases Information Center resources: Glomerulonephritis Membranous Nephropathy

U.S. FDA Resources

Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:

change in proteinuria from baseline to value at 3 months . [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Complete Remission(CR) or Partial Remission (PR) at 3 months [ Time Frame: 3 months ] [ Designated as safety issue: No ]
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 [ Time Frame: Throughout three months of this study and for nine months follow-up ] [ Designated as safety issue: Yes ]
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


Estimated Enrollment:	10
Study Start Date:	February 2010
Estimated Study Completion Date:	February 2013
Estimated Primary Completion Date:	January 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: ACTH (HP Acthar gel) 40 units	Drug: Adrenocorticotrophic hormone ACTH There will be two arms to the study: one arm receive 40 units and the second arm 80 units of the ACTH gel subcutaneously both given in a dose escalating frequency beginning at once every two weeks escalating to a maximum of twice per week over a total of three months exposed.An ammendment(approved by Health Canada and the UHN IRB allows an additional 1 month of the perscribed therapy of ACTH )if there is an improvement in proteinuria at the end of the 3 month exposure. Other Name: HP Acthar gel
Active Comparator: ACTH (HP Acthar gel) 80 units	Drug: Adrenocorticotrophic hormone ACTH There will be two arms to the study: one arm receive 40 units and the second arm 80 units of the ACTH gel subcutaneously both given in a dose escalating frequency beginning at once every two weeks escalating to a maximum of twice per week over a total of three months exposed.An ammendment(approved by Health Canada and the UHN IRB allows an additional 1 month of the perscribed therapy of ACTH )if there is an improvement in proteinuria at the end of the 3 month exposure. Other Name: HP Acthar gel

Arms

Assigned Interventions

Active Comparator: ACTH (HP Acthar gel) 40 units

Drug: Adrenocorticotrophic hormone ACTH

There will be two arms to the study: one arm receive 40 units and the second arm 80 units of the ACTH gel subcutaneously both given in a dose escalating frequency beginning at once every two weeks escalating to a maximum of twice per week over a total of three months exposed.An ammendment(approved by Health Canada and the UHN IRB allows an additional 1 month of the perscribed therapy of ACTH )if there is an improvement in proteinuria at the end of the 3 month exposure.

Other Name: HP Acthar gel

Active Comparator: ACTH (HP Acthar gel) 80 units

Drug: Adrenocorticotrophic hormone ACTH

There will be two arms to the study: one arm receive 40 units and the second arm 80 units of the ACTH gel subcutaneously both given in a dose escalating frequency beginning at once every two weeks escalating to a maximum of twice per week over a total of three months exposed.An ammendment(approved by Health Canada and the UHN IRB allows an additional 1 month of the perscribed therapy of ACTH )if there is an improvement in proteinuria at the end of the 3 month exposure.

Other Name: HP Acthar gel

Eligibility


Ages Eligible for Study:	18 Years to 72 Years (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01093157

Locations


Canada, Ontario
University Health Network- Toronto General Hospital
Toronto, Ontario, Canada, M5G2C4

Sponsors and Collaborators

University Health Network, Toronto

Mallinckrodt

Investigators


Principal Investigator:	Daniel Cattran, M.D	University Health Network, Toronto

More Information


Responsible Party:	University Health Network, Toronto
ClinicalTrials.gov Identifier:	NCT01093157 History of Changes
Other Study ID Numbers:	08-006328-GN Health Canada
Study First Received:	March 24, 2010
Last Updated:	January 14, 2013
Health Authority:	Canada: Health Canada

Keywords provided by University Health Network, Toronto:


Kidney disease, Glomerulonephritis

Additional relevant MeSH terms:


Glomerulonephritis Glomerulonephritis, Membranous Nephritis Kidney Diseases Urologic Diseases Autoimmune Diseases	Immune System Diseases Hormones Adrenocorticotropic Hormone Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 30, 2016