Acthar on Proteinuria in IgA Nephropathy Patients

• Status: Withdrawn
• Trial end date: 2020-01-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Baylor College of Medicine
• Treatments: Adrenocorticotropic Hormone

Criteria

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