Acthar on Proteinuria in IgA Nephropathy Patients
Acthar on Proteinuria in IgA Nephropathy Patients
IgA nephropathy occurs when IgA-a protein that helps the body fight infections-settles in the
 kidneys. IgA deposits may cause the kidneys to leak blood and sometimes protein in the urine.
 Proteinuria (abnormal amounts of protein in urine) can be a sign of kidney damage. Current
 treatments for IgA nephropathy is limited to Angiotensin Converting Enzyme (ACE) inhibitor
 medications with fish oil. ACE Inhibitors, also called ACEI medications, slows the
 angiotensin converting enzyme so that blood vessels can be relaxed.

 This study involves the study drugs, Acthar and Lisinopril (an ACEI medication routinely
 given for high blood pressure).

 In previous clinical studies, some subjects with IgA nephropathy have experienced reductions
 in proteinuria with consistent use of Acthar. Acthar is approved by the Food and Drug
 Administration (FDA) and used to treat patients with proteinuria.

 The purpose is to study the safety and effectiveness of the study drug Acthar given at
 different doses.
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