ACTHar in the Treatment of Lupus Nephritis

Systemic Lupus Erythematosus (SLE) is an autoimmune disease of unknown etiology that mainly
affects females of childbearing age. The disease is characterized by immune activation and
the development of autoantibodies.

About 50% of SLE patients experience inflammation of the kidneys. Lupus Nephritis (LN) is a
major cause of morbidity and mortality in patients with SLE. Mycophenolate Mofetil (MMF),
accompanied by Prednisone, is considered the current standard of care for LN. However,
long-term use of Prednisone has many serious side effects.

ACTHar Gel is an FDA approved drug comprised of an active substance called
adrenocorticotropic hormone (ACTH). ACTH belongs to an anti-inflammatory group called
melanocortins and carries out its effects by binding to five different melanocortin
receptors (MCRs). Specifically, ACTH binding to melanocortin 2 receptor subtype (MC2R) on
the adrenal cortex stimulates the production of cortisol that reduces inflammation in the
kidney. In addition to binding to melanocortin 1-5 receptor subtype (MC1-5R) and acting
directly on kidney tissues, ACTH may bind to MCRs on various cell types, such as immune
cells, and activate processes to protect the kidney.

This study will evaluate the most effective dose of ACTHar gel in proliferative LN (Class
III and IV) when given with MMF, the standard of care LN therapy. The intent of this study
is to determine the effectiveness and safety of ACTHar gel in an attempt to change the
clinical care requirements regarding steroid use in treating LN.

Inclusion Criteria:

1. Diagnosis of Systemic Lupus Erythematosus (SLE) by American College of Rheumatology
(ACR)/SLICC criteria

2. Age ≥ 16 years

3. Active lupus nephritis defined by:

a. Kidney biopsy documentation of International Society of Nephrology/Renal Pathology
Society (ISN/RPS) Class III or Class IV proliferative nephritis (including Class V
occurring in combination with Class III or IV) within 12 months and a urine
protein/creatinine ratio >1 at time of entry to study

4. Ability to provide informed consent

Exclusion Criteria:

1. Moderately severe anemia (Hgb < 8 mg/dL)

2. Neutropenia (< 1,000/mm3)

3. Thrombocytopenia (platelets < 50,000/mm3)

4. Positive purified protein derivative (PPD) test confirmed by positive Quantiferon TB
gold.

5. Pulmonary fibrotic changes on chest radiograph consistent with prior healed
tuberculosis

6. Active infections that in the opinion of the investigator increase the risks to the
subject.

7. Known human immunodeficiency virus (HIV) and hepatitis B or C

8. End-stage renal disease (estimated GFR clearance < 20 mL/min/1.73 m2)

9. History of cancer, except carcinoma in situ and treated basal and squamous cell
carcinomas

10. Pregnancy

11. Lactation

12. Unwillingness to use a medically acceptable form of birth control (including but not
limited to a diaphragm, an intrauterine device, progesterone implants or injections,
oral contraceptives, the double-barrier method, or a condom)

13. Previous failure to respond to MMF

14. Use of rituximab within the past year

15. Use of experimental therapeutic agents within the past 60 days

16. Greater than or equal to 5 times the upper limit of normal of liver function tests
(aspartate aminotransferase [AST], alanine aminotransferase [ALT], or alkaline
phosphatase)

17. Severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal,
pulmonary, cardiac, or neurological disease (or, in the investigator's opinion, any
other concomitant medical condition that places the participant at risk by
participating in this study) with the exception of diseases or conditions related to
active SLE

18. Current substance abuse