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

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ClinicalTrials.gov Identifier: NCT01093157
Recruitment Status : Completed
First Posted : March 25, 2010
Last Update Posted : May 4, 2017
Sponsor:
Collaborator:
Mallinckrodt
Information provided by (Responsible Party):
University Health Network, Toronto

Study Description
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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.


Condition or disease Intervention/treatment Phase
Glomerulonephritis Drug: Adrenocorticotrophic hormone ACTH Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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)
Study Start Date : February 2010
Actual Primary Completion Date : January 2013
Actual Study Completion Date : February 2013

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U.S. FDA Resources

Arms and Interventions
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Arm Intervention/treatment
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


Outcome Measures
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Primary Outcome Measures :
  1. change in proteinuria from baseline to value at 3 months . [ Time Frame: 3 months ]

Secondary Outcome Measures :
  1. Complete Remission(CR) or Partial Remission (PR) at 3 months [ Time Frame: 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%

  2. Adverse effects [ Time Frame: 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


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 72 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT01093157     History of Changes
Other Study ID Numbers: 08-006328-GN
Health Canada ( Registry Identifier: Health Canada 4727-88\3-23 C., control 131403 )
First Posted: March 25, 2010    Key Record Dates
Last Update Posted: May 4, 2017
Last Verified: January 2013

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