Efficacy and Safety Study of KIACTA in Preventing Renal Function Decline in AA Amyloidosis

• rate of change (slope) in creatinine clearance (CrCL) over time [ Time Frame: baseline to primary endpoint, measured every 3 months to end of study visit ] [ Designated as safety issue: No ]
• Progression to end-stage renal disease (ESRD) [ Time Frame: baseline, every 3 months to end of study visit ] [ Designated as safety issue: No ]
• estimated glomerular filtration rate (eGFR) [ Time Frame: screening, baseline, every 3 months, 12 months , early termination, treatment completion, end of study visit ] [ Designated as safety issue: No ]
• serum cystatin C over time [ Time Frame: baseline, every 3 months, 12 months, early termination, treatment completion, end of study visit ] [ Designated as safety issue: No ]
• urinary protein/creatinine ratio [ Time Frame: screening, baseline, every 3 months, 12 months, early termination, treatment completion, end of study visit ] [ Designated as safety issue: No ]
• serum amyloid A [ Time Frame: baseline, every 3 months, 12 months, early termination, treatment completion, end of study visit ] [ Designated as safety issue: No ]
• Time from baseline to persistent decrease in CrCL of 40% or more, a persistent increase in SCr of 80% or more, progression to ESRD, or all-cause mortality [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]

• persistent decrease in creatinine clearance (CrCl) of 40% or more [ Time Frame: baseline to primary endpoint, measured every 3 months to end of study visit ] [ Designated as safety issue: No ]
• peristent increase in Serum Creatinine (SCr) of 80% or more [ Time Frame: baseline to primary endpoint, measured every 3 months to end of study visit ] [ Designated as safety issue: No ]
• Progression to end-stage renal disease (ESRD) [ Time Frame: baseline, every 3 months to end of study visit ] [ Designated as safety issue: No ]
• estimated glomerular filtration rate (eGFR) [ Time Frame: screening, baseline, every 3 months, 12 months , early termination, treatment completion, end of study visit ] [ Designated as safety issue: No ]
• serum cystatin C over time [ Time Frame: baseline, every 3 months, 12 months, early termination, treatment completion, end of study visit ] [ Designated as safety issue: No ]
• urinary protein/creatinine ratio [ Time Frame: screening, baseline, every 3 months, 12 months, early termination, treatment completion, end of study visit ] [ Designated as safety issue: No ]
• serum amyloid A [ Time Frame: baseline, every 3 months, 12 months, early termination, treatment completion, end of study visit ] [ Designated as safety issue: No ]

The primary purpose of this study is to assess the efficacy and safety of treatment with Kiacta in adult patients with AA Amyloidosis.

• Drug: KIACTA (eprodisate disodium)
  Orally 1 to 3 capsules (Kiacta 400 mg) twice daily and adjusted as per the Creatine Clearance (CrCl) level increases or decreases.
• Drug: Placebo
  Orally 1 to 3 capsules (placebo) twice daily and adjusted as per the Creatine Clearance (CrCl) level increases or decreases:

• Experimental: Kiacta (eprodisate disodium)
  Intervention: Drug: KIACTA (eprodisate disodium)
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

Inclusion Criteria:

• females must be of nonchildbearing potential (more than 1 yr postmenopausal)or use effective contraception for at least 2 months prior to the baseline visit and through 30 days after the last dose of study medication
• confirmed diagnosis of AA amyloidosis demonstrated by positive biopsy using congo red staining and immunohistochemistry or immunoelectronmicroscopy. Mass spectroscopy will be used upon approval of the sponsor on a case to case basis.
• persistent proteinuria greater than 1 g/24h at 2 distinct 24-hr urine collections
• must have CrCl greater than 25 ml/min/1.73 m2 at 2 distinct 24 hr urine collections

Exclusion Criteria:

• evidence or suspicion of chronic kidney disease secondary to a disease other than AA amyloidosis (eg, diabetes, long-standing uncontrolled hypertension, polycystic kidney disease, recurring polynephritis, or systemic lupus erythematosus)
• history of kidney transplantation
• evidence or suspicion of a cause of potentially reversible acute renal failure within 3 months prior to baseline visit
• presence of concomitant diseases or medication that could interfere with the interpretation of study results or compromise patient safety
• presence of condition that could reduce life expectancy to less than 2 yrs
• Type 1 or 2 diabetes mellitus
• significant hepatic enzyme elevation
• unstable angina, myocardial infarction, coronary artery bypass graft surgery, or percutaneous transluminal coronary angioplasty within 6 months prior to the baseline visit; presence of NY Heart Assoc class III or IV heart failure
• presence of, or history of stroke or transient ischemic attack within 6 months prior to baseline visit
• initiation of, or any changes in, angiotensin converting enzyme inhibitor, angiotensin II receptor antagonist therapy, or renin inhibitor within 3 months prior to baseline visit
• initiation of, or any changes in, cytotoxic agents, anti-tumor necrosis factor agents, anti interleukin-1 or 6 agents, or colchicine therapy within 3 months prior to baseline visit
• previous use of Kiacta
• history of malignancy within 5 yrs prior to study entry, except for cervical carcinoma in situ, nonmelanomatous carcinoma of the skin, or ductal carcinoma in situ of the breast that has been surgically cured
• use of investigational drug within 30 days prior to the first screening visit
• active alcohol and/or drug abuse