Acthar for Treatment of Proteinuria in Diabetic Nephropathy Patients

Inclusion Criteria (numbers 2, 3, 4, 5, 6, and 7 per protocol):

• Body mass index ≤ 45 kg/m2 at screening.
• Diagnosis of T1DM or T2DM, with HbA1c ≤ 9.0% at Visit 1A. Diagnosis of T2DM should have been made at > 30 years of age (if diabetes developed at a younger age, C-peptide level may be obtained to confirmed the diagnosis).

• Currently insulin-requiring

  • Patients on oral hypoglycemic therapy plus insulin are eligible provided that oral hypoglycemic agent(s) administered and the dosing regimen(s) of oral hypoglycemic therapy have been stable for ≥ 12 weeks prior to screening. No changes in oral hypoglycemic therapy should be planned or anticipated during the treatment period.

• Renal Target Disease Requirements:

  • The average of two eGFR values collected during screening (Visits 1 and 1A) must be between 20-60 mL/min/1.73m2 (calculated using the abbreviated Modification of Diet in Renal Disease [MDRD] equation AND
  • Protein to creatinine ratio (PCR) ≥ 3.0 g/g OR total urine protein ≥ 3.0 g from the 24-hour urine collection returned at Visit 1A.

• Antihypertensive Therapy:

  • Treatment with an ACEI and/or an ARB for at least 6 weeks prior to screening Visit 1A, with stable maintenance dose for ≥ 14 days prior to screening Visit 1A. No change in ACEI or ARB therapy should be planned or anticipated for the period of the study.
  • If treated with additional antihypertensive therapy(ies), duration of therapy ≥ 30 days prior to screening Visit 1A, with stable maintenance dose for ≥ 14 days prior to screening Visit 1A.
  • If the patient has documented intolerance to ACEI and/or ARB therapy (e.g. angioedema, hyperkalemia), they may be eligible for study entry, but the Medical Monitor must be consulted in these cases prior to randomization.
• Mean systolic blood pressure ≤ 140 mmHg and diastolic blood pressure ≤ 90 mmHg on ≥ 3 seated readings taken at least 5 minutes apart during the screening period at Visit 1A.

Exclusion Criteria (numbers 2, 3, 4, 5, 7, and 11 per protocol):

• Therapies and/or Medications:

  • History of prior sensitivity to Acthar or other porcine protein products.
  • Chronic systemic corticosteroid use, defined as ≥ 20 mg of prednisone or equivalent systemic corticosteroid taken for more than 4 consecutive weeks within 6 months prior to randomization. Topical, inhaled, or intra-articular corticosteroids are allowed.
  • Planned treatment with live or live attenuated vaccines once enrolled in the study.
  • Previous treatment on a drug being investigated for the treatment of diabetic nephropathy within 6 months prior to randomization.

• Contraindication to Acthar per Prescribing Information Section 4: scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of peptic ulcer, congestive heart failure, uncontrolled hypertension, primary adrenocortical insufficiency, or adrenal cortical hyperfunction.

  • For the purpose of this study, history of peptic ulcer is defined as ≤ 6 months prior to Visit 1A.

• Diabetes Target Disease Exceptions:

  • Severely uncontrolled diabetes mellitus as judged by the Principal Investigator
  • HbA1c > 9% at screening Visit 1A.
  • Fasting serum glucose > 230 mg/dL at BOTH screening Visits 1 and 1A.
  • History of diabetic ketoacidosis or non-ketotic hyperosmolar coma within 6 months of screening.
  • History of ocular laser photocoagulation therapy within 6 months of screening OR diabetic retinopathy, diabetic macular edema, or cataracts associated with impairment of visual acuity that will affect adherence with the dosing or administration of SC injections.
  • Patients unwilling to titrate insulin for blood glucose control if adjustment of hypoglycemic therapy is required during the study.

• Renal Target Disease Exceptions:

  • History of clinical or renal biopsy evidence of non-diabetic renal disease
  • Patients requiring diagnostic or interventional procedure requiring an intravenous contrast agent must delay screening/randomization for at least 14 days
• Tuberculosis: Any patient with a positive Interferon-gamma release assay, OR signs and symptoms concerning for active tuberculosis.

• Cardiovascular:

  • History of congestive heart failure (NYHA Functional Class III-IV).

  • History of dilated cardiomyopathy with ejection fraction < 40%.

    1. Exceptions require approval by the Medical Monitor.

  • Patient has had any of the following within 3 months of screening:

    1. Unstable angina
    2. Myocardial infarction
    3. Coronary artery bypass graft or percutaneous transluminal coronary angioplasty
    4. Transient ischemic attack or cerebrovascular accident
    5. Unstable arrhythmia