Idiopathic Focal Segmental Glomerulosclerosis (FSGS) and Treatment With ACTH

EXPERIMENTAL TREATMENT: Patients with biopsy proven FSGS will be treated with ACTH in an
open-label pilot study of tolerability and efficacy. The investigators will recruit 18-20
patients to complete this study, over 2 years.

ACTH therapy: Patients will receive H.P. Acthar gel IM or SQ, initially at 40 IU SQ every
week for 16 weeks of therapy. All patients will be treated to goal BP of <140/90mmHg with
all patients treated with ACEi or ARB therapy as tolerated. H2 receptor blockade or proton
pump inhibitor therapy will also be offered all patients. Dose will be titrated up to 160 IU
SQ every week, if at 1 month the patient has had no substantial reduction in proteinuria, no
deterioration of blood pressure and no development of hyperglycemia as well as no serious
adverse events felt to be related to the medication.

CLINICAL OUTCOME: Patients will be followed for the primary outcome of remission of
proteinuria. This will be defined as partial remission when the proteinuria is reduced below
50% of the initial, pre treatment value and as complete remission when the proteinuria is
reduced to < 0.5 g/g or <500 mg/day on a 24 hour urine sample. Secondary outcomes will
include effects on eGFR, effects on glucose levels, effects on blood pressure (total doses
of antihypertensive medications and absolute changes in blood pressure) and on immune
status. Outcomes will be determined by looking at 3 month and 6 month values of urine
protein and eGFR following initiation of treatment.

IMMUNOLOGIC TESTING: In order to further assess the role of immunologic perturations on FSGS
and the effect of ACTH on the immune system, all patients will bank blood and urine before
the start of the study for cytokine analysis, RNA, DNA, protein and protoarray testing.

MONITORING AND SAFETY: All patients will undergo full informed consent per the Stanford
Institutional Review Board. Contact numbers will be provided and study staff will be
available at all times in case of any medical emergencies. All patients will continue with
routine health monitoring with a minimal of monthly assessments. A comprehensive interview
will be undertaken to assess for side effects, complete physical exams will be accomplished
including vital signs, CBC, clinical chemistries (including electrolytes, creatinine,
glucose and liver function tests), urine for protein and creatinine and fasting lipid
profiles every 3 months. Also at screening and baseline.

PATIENT WITHDRAWAL/TERMINATION OF STUDY: Patients will be closely monitored, as detailed
above. Patients may voluntarily leave the study at any time, although every effort will be
made to follow their clinical course and monitor for safety issues and possible benefits of
therapy. Patient will be monitored for adverse events. Patients with severe adverse events
will be evaluated for the relatedness of their event to the study medication. If the event
is considered severe and possibly or probably related to the study medication, the
medication will be discontinued and the patient will continue to be monitored. In the case
the adverse event is possibly related, the medication may be restarted, if the investigator
and subject agree. For patients with probably related severe adverse events, study treatment
will be discontinued however, the investigators will still follow the patient to see if the
course of their underlying disease was modified by treatment. As this is an open label,
pilot study, no data safety monitoring board is felt to be necessary. If drug related SAEs
develop in more than 20% of patients, the study will be submitted back to the IRB to
determine if it should continue.

Inclusion Criteria:

- 1. Biopsy proven FSGS

- 2. Ability to consent and complete study evaluations

- 3. Greater than 2g/day of proteinuria

- 4. No contraindications to treatment with corticosteroids or ACTH

- 5. Women of childbearing potential will agree to use effective forms of birth control
throughout this study

Exclusion Criteria:

- 1. Known secondary cause of FSGS

- 2. Receiving active immune therapy (within 90 days)

- 3. Pregnancy

- 4. Creatinine >2.5 mg/dl

- 5. Uncontrolled HTN (>180/100mm Hg)

- 6. Diabetes

- 7. Acute or chronic infection

- 8. Severe comorbidity (active coronary, cerebrovascular disease, cancer, psychiatric
disease)

- 9. Age < 16, >65 years

- 10. Evidence of untreated tuberculosis (+PPD or Ellispot Gold testing)

- 11. A known contraindication to ACTH. Corticotropin is considered contraindicated in
patients with scleroderma, osteoporosis, systemic fungal infections, ocular herpes
simplex, recent surgery, history of or the presence of a peptic ulcer, congestive
heart failure, uncontrolled hypertension, or sensitivity to proteins of porcine
origin.