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

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

Official Title
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International Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of the Efficacy and Safety of KIACTA in Preventing Renal Function Decline in Patients With AA Amyloidosis

Conditions
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Amyloidosis

Intervention / Treatment
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* Drug: KIACTA (eprodisate disodium)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Kiacta (eprodisate disodium)<br> | Drug: KIACTA (eprodisate disodium)<br>* Orally 1 to 3 capsules (Kiacta 400 mg) twice daily and adjusted as per the Creatine Clearance (CrCl) level increases or decreases.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Orally 1 to 3 capsules (placebo) twice daily and adjusted as per the Creatine Clearance (CrCl) level increases or decreases:<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from baseline to a persistent decrease in Creatinine clearance (CrCL) of 40% or more, a persistent increase in Serum Creatinine(SCr) of 80% or more, or progression to end-stage renal disease(ESRD) |  | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rate of change (slope) in creatinine clearance (CrCL) over time |  | baseline to primary endpoint, measured every 3 months to end of study visit | 
| Progression to end-stage renal disease (ESRD) |  | baseline, every 3 months to end of study visit | 
| estimated glomerular filtration rate (eGFR) |  | screening, baseline, every 3 months, 12 months , early termination, treatment completion, end of study visit | 
| serum cystatin C over time |  | baseline, every 3 months, 12 months, early termination, treatment completion, end of study visit | 
| urinary protein/creatinine ratio |  | screening, baseline, every 3 months, 12 months, early termination, treatment completion, end of study visit | 
| serum amyloid A |  | baseline, every 3 months, 12 months, early termination, treatment completion, end of study visit | 
| 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 |  | Up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kiacta for AA amyloidosis