Pilot Study of ACTH in the Treatment of Immunoglobulin A (IgA) Nephropathy at High Risk of Progression

An Open-Label Pilot Study of ACTH in the Treatment of IgA Nephropathy at High Risk of Progression

This study is designed to answer whether patients with progressive IgA nephropathy, who receive Acthar (ACTH) gel injection at a dose of 80 units subcutaneously twice weekly for 6 months is effective in inducing improvement in proteinuria and renal function.

Study Overview

• Status: Completed
• Conditions: Proteinuria; Progressive IgA Nephropathy
• Intervention / Treatment: Drug: ACTH (Acthar) Gel

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion:

• Proteinuria > 1000 mg/24h despite documented ACEi/ARB therapy and adequate blood pressure control for > 3 months.
• Quantified 24h creatinine clearance > 30 ml/min/1.73m2.
• Blood pressure < 130/80 mmHg at > 75% of the readings.
• Henoch Schoenlein Purpura (HSP): Patients with biopsy proven IgA nephropathy and clinical features consistent with Henoch Schonlein Purpura will be considered eligible for the study.
• Patient must be able to receive injections to be enrolled in the study.
• Patient must have a kidney biopsy slide on file - that can be sent to Mayo Clinic.

Exclusion:

• Clinical and histologic evidence of IgA predominant Lupus nephritis
• Patients with greater than 50% glomerular senescence or cortical scarring on renal biopsy.
• Serum Cr > 3.0 mg/dL or creatinine clearance glomerular filtration rate (GFR) < 30 ml/min at the time of screening
• Patients with history of Crohn's disease or Celiac Sprue
• Clinical evidence of cirrhosis, chronic active liver disease.
• Known infection with hepatitis B, hepatitis C, or HIV (Patients will be serologically screened prior to study entry (if the rest has been completed in the last two years, the patient will not have to undergo additional testing).
• Active systemic infection with bacterial, viral, fungal, or mycobacterial or atypical mycobacterial infections (excluding fungal infections of nail beds).
• Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening.
• Positive pregnancy test or breast feeding at time of study entry (urine pregnancy test will be performed for all women of childbearing potential no later than 7 days prior to treatment) or patients unwilling to comply with contraceptive measures as outlined above.
• Patients receiving therapy with oral prednisone or glucocorticoid equivalent in the past 3 months.
• Patients who had received immunosuppressive therapy including cyclophosphamide, mycophenolate mofetil (MMF), cyclosporine, tacrolimus or azathioprine in the last 6 months.
• Current or recent (within 30 days) exposure to any investigational drug.
• Patients having received a live vaccine within 28 days of study enrollment.
• Hemoglobin: < 8.5 gm/dL
• Platelets: < 100,000/mm
• Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) > 2.5 x Upper Limit of Normal
• Patients with anaphylaxis and/or known allergic reactions to ACTH
• Previous Treatment with ACTH
• History of drug, alcohol, or chemical abuse within 6 months prior to screening
• Concomitant or previous malignancies, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
• History of psychiatric disorder that would interfere with normal participation in this protocol.
• Significant cardiac or pulmonary disease (including obstructive pulmonary disease).
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complication.
• Inability to comply with study and follow-up procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ACTH Gel; Injected does of 80 units subcutaneously twice weekly for 6 months.	Drug: ACTH (Acthar) Gel; Injected dose of 80 units subcutaneously twice weekly for 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With a Complete or Partial Response to Treatment	A complete response is defined by <300 mg proteinuria/24 hours and no greater than a 10% reduction in glomerular filtration rate (GFR) as determined by quantified creatinine clearance. A partial response is defined by >50% reduction in 24 hour proteinuria and no greater than a 25% reduction in baseline GFR as quantified creatinine clearance. No response is defined by < or equal to 50% reduction, unchanged or increasing proteinuria over baseline levels and a greater than a 25% reduction in baseline GFR as quantified creatinine clearance.	12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects to Develop an Infection	The number of subjects with infections was defined as the development of pneumonia or complicated urinary tract infection/Pyelonephritis	12 months

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: Mallinckrodt
• Investigators: Principal Investigator: Fernando Fervenza, MD, PhD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2015
• Primary Completion (Actual): June 30, 2018
• Study Completion (Actual): June 30, 2018

Study Registration Dates

• First Submitted: October 31, 2014
• First Submitted That Met QC Criteria: November 4, 2014
• First Posted (Estimate): November 5, 2014

Study Record Updates

• Last Update Posted (Actual): June 26, 2019
• Last Update Submitted That Met QC Criteria: June 4, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Progressive; renal function; Nephropathy; ACTH; IgA; Acthar
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Urological Manifestations; Urination Disorders; Nephritis; Glomerulonephritis; Kidney Diseases; Proteinuria; Glomerulonephritis, IGA
• Other Study ID Numbers: 14-006965