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