Acthar on Proteinuria in IgA Nephropathy Patients

Participation in this study may last up to 2 years (from first visit to final visit) and
includes 10 study visits and 8 phone calls.

Subjects will be randomly assigned to one of two treatment groups:

Group A will receive Acthar 80 unit injection 2 times per week or

Group B will receive Acthar 80 unit injection 3 times per week

All participants will be prescribed Lisinopril (10mg per day or higher depending on your
blood pressure) as part of regular care for their condition. If they are already on another
ACEI, Lisinopril will be prescribed. If subjects are unable to tolerate Lisinopril or other
ACEI medications, an angiotensin receptor blocker (ARB) will be prescribed. ARBs are another
type of medication that also helps relax blood vessels if subjects cannot tolerate ACEI
medications.

Regardless of which treatment group subjects are assigned,everyone will self-inject the
study drug using a subcutaneous (SC) injection under the skin using a needle and syringe.
Subjects will be trained on the proper technique to be used for each injection before taking
study drug home. Enough of the study drug will be given to take home (based on which group
the subject is in) to administer until they are seen in 3 months for their next study visit.

Blood samples will be taken for lab tests at each visit and biomarkers (Screening Visit and
Visit 9). Women of childbearing potential will also have a pregnancy test done.
Approximately 4 teaspoons of blood will be drawn for the Screening Visit and Visit 9.

Subjects must fast at least 8 hours prior to the blood draw.

The following study procedures will be performed:

SCREENING VISIT:

- Informed consent will be obtained;

- Inclusion/exclusion criteria will be assessed, demographics and medical history will be
collected (including PCR and urinalysis results as these tests are routinely done as
part of regular care);

- Pregnancy test if subject is a female of child bearing potential;

- Physical exam;

- Height/Weight collected;

- Vital signs will be obtained. Blood pressure will be recorded.

- Blood samples collected for study specific tests (aldosterone and cortisol)
(approximately 2 teaspoons) and biomarkers (approximately 2 teaspoons). No more than
approximately 4 teaspoons will be collected at this study visit;

Subjects who do not meet eligibility criteria during the initial screening attempt will be
permitted to rescreen 2 times, for a total of 3 screening attempts. Rescreen subjects must
first be registered as screen failed in the CTMS system and subsequently registered as a
rescreen subject. Once the subject is registered as rescreened, all screening procedures
will need to be repeated.;The exact time interval of each re-screen would be at the
discretion of the investigator. Completion of rescreen would be no greater than 6 months
from the initial screening date.

VISIT 1 (BASELINE, DAY 0)

- Pregnancy test if subject is a female of child bearing potential

- The first study drug dose in the clinic under the supervision of the study staff.
Subject will remain at the clinic for at least 1 hour for monitoring of any allergic
reaction.

- Subjects will receive enough study drug (8 for those dosing twice a week and 11 for
those dosing three times a week) to take home until their next visit in 3 months.
Subjects will also receive a dosing diary to keep track of each dose taken and any side
effects they may feel. Subjects will bring dosing diary with them to each study visit
on Visits 2-5.

A member of the study staff will also call subjects once a week for the first 4 weeks after
starting study drug (Visit 1) to make sure they are taking the study drug as required,
completing the dosing diary, if they are taking any other medications and if they are
experiencing any side effects. There will be 4 phone calls between Visit 1 and Visit 2.

VISITS 2-5 ONLY (MONTHS 3, 6, 9, 12)

- Dosing diary is collected

- Study medication accountability is recorded.

- Pregnancy test if subject is a female of child bearing potential

- Acthar medication is dispensed (Visits 2-4 only)

- Kidney biopsy performed - Visit 5 only

Kidney biopsy procedure:

Subjects will have to go to nearby hospital within 1 week of completing Visit 5 to have this
outpatient procedure done. Subjects will be asked to lie on their stomach face down with a
pillow under their rib cage for at least 20 to 30 minutes. Ultrasound may be used to find
the proper biopsy site. A local numbing medicine (anesthetic) will be injected under their
skin near the biopsy area.

The hospital staff will make a tiny cut in the skin and insert a biopsy needle into the area
and to the surface of the kidney. Subjects will be asked to take a deep breath and hold
breath as a thin needle is passed through the skin into the kidney. Inside the needle is a
sharp edge that will remove small pieces of the kidney. The biopsy needle will then be
withdrawn, and pressure will be applied to the biopsy site to stop the minor bleeding that
usually occurs after the biopsy. After the procedure, a bandage will be applied to the
biopsy site.

The hospital staff will give subject numbing or pain medicines as needed.

VISITS 2-9 (MONTHS 3, 6, 9, 12, 15, 18, 24)

- Inclusion/exclusion criteria will be assessed, demographics and medical history will be
collected;

- Physical exam;

- Height/Weight collected;

- Vital signs will be obtained. Blood pressure will be recorded.

- Blood samples collected for study specific tests (aldosterone and cortisol)
(approximately 2 teaspoons). Biomarkers (approximately 2 teaspoons) will also be
collected at Visit 9. No more than approximately 4 teaspoons will be collected at Visit
9;

After Visit 2, a member of the study staff will continue to call you about every 1 ½ months
to make sure subjects are taking the study drug as required, if subjects are taking any
other medications and if they are experiencing any side effects. There will be 4 more phone
calls that will occur between Visit 2-3, Visit 3-4, Visit 4-5 and Visit 5-6. Subjects will
receive a total of 8 phone calls during this study.

The total amount of blood collected over the course of this study is no more than
approximately 38 teaspoons.

Treatment with the study drugs will continue for the first 12 months of participation in
this study. If subjects do not respond after 3 months of treatment or only partially respond
to the treatment, dosage may be increased (up to 120 unit injections twice a week for 3
months). If subjects still do not respond at the increased dose, the study drug will be
discontinued after another 3 months of treatment.

If subjects respond to the treatment during the 12 months of treatment but then their
response goes away during the follow up period, they will be placed back on study drug for
an additional 6 months.

If, for any reason, the study drug is stopped before the last treatment visit, subjects will
be asked to come into the clinic to complete study procedures. Subjects will be asked to
have all end-of-study testing done for safety.

Acthar cannot be abruptly stopped and must be gradually lessened. Except if subjects are
experiencing an allergic reaction, the drug will be administered at half the dose for 1
week, then ¼ dose for another week, then stopped.

If subjects are on insulin or other oral antidiabetic medications, Acthar may decrease
glucose (sugar) tolerance. This may result in an increase blood sugar. Subjects will be
asked to let the study doctor know if they are on these medications to discuss glucose
monitoring and a plan on how to keep taking these medications while on Acthar and what to do
if they experience an increase in blood sugar.

Inclusion Criteria:

1. Signed informed consent prior to any study specific procedures

2. Male and females aged 18 years and older

3. BMI 40 kg/m2 or less

4. History of nephrotic syndrome due to IgA (confirmed from renal biopsy performed
within last 5 years)

5. Protein to creatinine (PCR) ratio 2.5 g/g or more (spot urine)

6. Estimated GFR (eGFR) greater than 30 mL/min/1.73/m2 (as calculated using the
abbreviated Modification of Diet in Renal Disease [MDRD] equation as per
http://www.kidney.org/professionals/kdoqi/gfr_calculator.cfm).

7. Any prior course of therapy with (but not within the last 3 months): steroids,
cyclophosphamide, chlorambucil, cyclosporine or tacrolimus ). If, after f/u period,
it was determined that subject did not achieve a complete or partial response,
subject will be eligible for this study.

8. Antihypertensive treatment including use of Angiotensin-converting enzyme inhibitors
(ACEI) and/or Angiotensin receptor blockers (ARB):

- Unless there is a history of intolerance to ACEI or ARB therapy, the subject
must be treated with at least one of these agents,

- Treatment with ACEI and/or ARB for 3 months or more prior to Visit 1, with
stable maintenance dose(s) for 30 days or more prior to Visit 1,

- If treated with other antihypertensive therapies, treatment duration of 30 days
or more and stable maintenance dose for 7 days or more prior to Visit 1; and

9. Blood pressure determined by the average of 3 or more seated readings taken 5 minutes
or more apart at Visit 1:

- Mean systolic blood pressure 140 mmHg or less and

- Mean diastolic blood pressure 80 mmHg or less.

10. Subjects must have the following laboratory results for study inclusion:

- Hemoglobin 9 g/dL or more

- Platelets 100 X 10^3 cells/mu-L

- AST 2x ULN or less

- ALT 2x ULN or less

- Total bilirubin 2x ULN or less

- HgbA1c less than 6.5%

Exclusion Criteria:

1. Inability or refusal to give informed consent

2. Unwillingness to receive or intolerant of SC injections of study medication

3. Use of disease modifying agent within "delayed effect" 1 month of Visit 1 with:
glucorticoids, cyclophosphamide, cyclosporine, cellcept

4. Therapies and/or medications:

- History of previous use of Acthar for treatment of nephrotic syndrome

- Prior sensitivity to Acthar or other porcine protein products

- Planned treatment with live or live attenuated vaccines once enrolled in the
study

5. Chronic systemic corticosteroid use, defined as any dose of systemic corticosteroid
taken for more than 4 consecutive weeks within 1 month prior to Visit 1 (use of
topical, inhaled, or intra-articular corticosteroids is allowed)

6. Planned treatment with live or live attenuated vaccines once enrolled in the study.

7. Contraindication to Acthar per Prescribing Information*

8. For the purpose of this study: history of peptic ulcer is defined as 6 months or less
prior to Visit 1.

9. Renal target disease exclusions*

10. Out of control or severe hypertension

11. History of Systemic Lupus Erythematosus

12. Uncontrolled Type 1 or type 2 diabetes mellitus (prior diagnosis of gestational
diabetes mellitus is not an exclusion)

13. History of Deep Vein Thrombosis (DVT) 6 months or less prior to Visit 1

14. Presence of renal vein thrombosis:

- Known current diagnosis by ultrasound, magnetic resonance imaging (MRI) or
computed tomography scan

- Signs or symptoms consistent with occurrence of acute renal vein thrombosis
(hematuria in combination with flank pain and >30% unexplained acute rise in
serum creatinine) with renal vein thrombosis confirmed by ultrasound, MRI or
computed tomography scan

15. Reproductive status:

- Women who are pregnant

- Women who are breastfeeding

- Women of childbearing potential who are unwilling or unable to use an acceptable
method of birth control to avoid pregnancy for the entire study period, as
evaluated by the Investigator (women who are not of childbearing potential are
those that have a history of hysterectomy, bilateral oophorectomy, or are
postmenopausal with no history of menstrual flow for 12 months or more prior to
Visit 1

16. Chronic active hepatitis C or B infection

17. Known immunocompromised status, including but not limited to individuals who have
undergone organ transplantation or who are known to be positive for human
immunodeficiency virus

18. Undergoing or have received therapy for solid tumor malignancy 5 years or less prior
to Visit 1 (with the exception of treated and cured basal cell or treated and cured
squamous cell carcinoma)

19. Undergoing or have received therapy for blood malignancy 5 years or less from Visit 1

20. Cardiovascular:

- History of or active congestive heart failure (NYHA Functional Classification
Class II through IV) on http://sscts.org/ClassificationHeartFailureNYHA.aspx

OR

- History of known dilated cardiomyopathy with left ventricular ejection fraction
30% or less

OR

- Occurrence of any of the following within 3 months of Visit 1:

- Unstable angina

- Myocardial infarction

- Coronary artery bypass graft or percutaneous transluminal coronary
angioplasty

- Transient ischemic attack or cerebrovascular disease; or Unstable
arrhythmia

21. Administration of any other investigational medication or participation in an
interventional clinical research study within 30 days of Visit 1

22. Abuse of alcohol or other substance abuse within the 6 months prior to Visit 1 as
determined by the Investigator

23. Subject is a participating Investigator, study coordinator, employee of an
Investigator, or immediate family member of any of the aforementioned