Safety and Efficacy of Acthar Gel in an Outpatient Dialysis Population

Recent reports demonstrated Acthar gel is effective to induce remission of proteinuria in
the Nephrotic Syndrome patients (Bomback 2011, 2012). There are limited published reports
documenting the clinical response (creatinine, proteinuria, serum albumin and cholesterol)
to ACTHAR therapy in a non-diabetic hemodialysis population. In addition to renal
dysfunction and high risk for mortality, individuals who receive dialysis also have
decreased strength, low exercise capacity, poor physical functioning, and a low quality of
life (Edgell 1996, Johansen, 2001). Strength deficits are well documented in those with End
Stage Renal Disease [ESRD] (Cheema 2010, Yoda 2012). There are several reports documenting
an association between strength and gait deficits and other measures of physical performance
in persons with ESRD (Bohannon 1994, Fitts 1997, Segura-Orti 2011). It is well known that
measures of physical performance may predict risk for fall and hospitalization in older
individuals (Guralnik JM, 2000).

Deficits to physical performance may be further compounded by poor nutritional status.
Persons with chronic renal disease, particularly in the context of hemodialysis or chronic
renal replacement therapy, are often malnourished and/or are affected by abnormal
micronutrient status (McMahon 2012). Furthermore, previous studies have shown that more than
a third of acute-care, nephrology-related admissions are characterized by malnutrition (Lim
2012), and that it affects from 23% - 76% of all patients receiving hemodialysis (including
outpatients)(Blumenkrantz 1980, Ikizler 1996, Pecoits-Filho 2002).

Decreased functional status and concomitant malnutrition contribute to increased hospital
readmissions, prolonged length of stay (and inevitably, increased medical costs), and
increased morbidity and mortality patients (Isabel 2003, Lim 2012). Given the high
prevalence of these characteristics in persons with renal disease, it is important to
prioritize identification of novel and effective means by which to sustain and improve the
functional capability of these patients, and to maintain their nutritional status and
attenuate malnutrition.

To date, there are no reports of the impact of Acthar gel therapy on renal function,
strength, physical performance, nutritional status and quality of life in NDHD patients.
This study will determine if Acthar gel therapy will maintain or improve overall kidney
function as measured with 24 hour urine study at baseline and at the end of study period. In
addition this study will determine if Acthar gel therapy will improve nutritional, physical
and biochemical status in an outpatient non-diabetic hemodialysis population.

Inclusion Criteria:

- Inclusion criteria will be individuals requiring dialysis for treatment of ESRD who
have had poor response to immunosuppressive strategies.

- Non-Diabetic

- Adults age 18-80

Exclusion Criteria:

- receiving hemodialysis for > 5 years

- diabetic, less than 18 years of age

- are pregnant

- have a history of cancer in the last 5 years

- have an active infection

- have recently had a myocardial infarction (within 6 weeks)

- have malignant arrhythmias, unstable angina, uncontrolled hypertension (SBP> 180
and/or DBP > 105)

- recent hospitalization (< 30 days),

- ocular disease,

- accelerated osteoporosis,

- gastrointestinal diseases (ulcerative colitis, diverticulitis, myasthenia gravis)

- any disorder that may be exacerbated by short periods of activity.

- cognitive dysfunction

- neurological deficits leading to limited ambulation.