Health Condition 1: null- AA Amyloidosis
Conditions
Interventions
Intervention1: 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.
(Duration 24 months)
Con
Sponsors
Auven Therapeutics Development Switzerland SARL
PPD Pharmaceutical Development India Private Limited
Eligibility
Inclusion criteria
Inclusion criteria: All tests to confirm patients eligibility must be performed during the screening period defined as 3 months prior to the baseline visit and up to 1 week prior to the baseline visit. To be eligible to participate in the study, patients must meet all of the criteria listed below: a) Patients must be at least 18 years of age and no more than 80 years of age. b) Patients are males or non pregnant, non lactating females. - Women must be of nonchildbearing potential (ie, more than 1 year 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 as follows: i. Oral contraception with an additional barrier method (since the investigational product may impair effectiveness of oral contraception) ii. Double-barrier method (diaphragm with spermicidal gel or condom with contraceptive foam) iii. Transdermal or long-acting injected contraceptive (eg, depot medroxyprogesterone acetate [Depo Provera]) iv. Intrauterine device or implantable contraceptive v. Partner who is surgically sterile (vasectomy) vi. Total abstinence. - A woman of childbearing potential must have a negative serum pregnancy test at the first screening visit. Urine pregnancy tests will also be performed at every subsequent visit. Should a patient become pregnant during the study, study medication will be discontinued and the patient will be withdrawn from the study and followed-up by research personnel until delivery. Pregnant women will be contacted by telephone every 3 months until delivery. - Male patients with partners of childbearing potential must be surgically sterile or use a contraceptive method as previously described. c) Patients must have a confirmed diagnosis of AA amyloidosis demonstrated by positive biopsy using Congo red staining and immunohistochemistry or immunoelectron microscopy during the screening period. Tissue from previous biopsy or written pathology report confirmation of a previous biopsy can be used for confirmation of diagnosis, if available. d) Patients must have persistent proteinuria defined as urinary protein excretion >=1 g/24 h at 2 distinct 24-hour urine collections at least 1 week apart during the screening period. e) Patients must have CrCl >=25 mL/min/1.73 m2 at 2 distinct 24-hour urine collections at least 1 week apart during the screening period. f) Patients must have the ability and willingness to provide informed consent and to comply with all study procedures. Note: As per the Indian Regulatory (DCGI) Approval for the study, patients aged >= 18 yrs and <= 75 yrs should be included in the study.
Exclusion criteria
Exclusion criteria: A patient meeting any of the criteria listed below during the screening period will not be eligible to participate in the study and will not be randomly assigned to treatment. Some of these criteria, as indicated below, will need to be reconfirmed at the baseline visit prior to providing the patient with study medication. a) Evidence or suspicion of chronic kidney disease secondary to a disease process other than renal AA amyloidosis (eg, diabetes, long-standing uncontrolled hypertension, polycystic kidney disease, recurring polynephritis, or systemic lupus erythematosus). b) History of kidney transplantation. c) Evidence or suspicion of a cause of potentially reversible acute renal failure, such as uncontrolled hypertension, urinary tract infection, or drug nephrotoxicity within 3 months prior to the baseline visit. d) Presence of concomitant diseases or concomitant medication that could interfere with the interpretation of study results or compromise patient safety. To be reconfirmed at the baseline visit. e) Presence of conditions that could reduce life expectancy to less than 2 years. To be reconfirmed at the baseline visit. f) Presence of type 1 or type 2 diabetes mellitus. g) Presence of significant hepatic enzyme elevation (as defined by aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase more than 5 times the upper limit of normal and/or total bilirubin 50% above the upper limit of normal) or presence of cirrhosis. h) Presence of unstable angina, myocardial infarction, coronary artery bypass graft surgery, or percutaneous transluminal coronary angioplasty within 6 months prior to the baseline visit. i) Presence of, or history of, stroke or transient ischemic attack within 6 months prior to the baseline visit. j) Presence of New York Heart Association class III or IV heart failure (Section 13.1). k) Use of any investigational drug within 30 days prior to the first screening visit. To be reconfirmed at the baseline visit. l) Active alcohol and/or drug abuse. m) Initiation of, or any changes in, angiotensin converting enzyme inhibitor, angiotensin II receptor antagonist therapy, or renin inhibitor within 3 months prior to the baseline visit. n) Initiation of, or any changes in, cytotoxic agents, anti-tumor necrosis factor agents, anti-interleukin-1 or anti-interleukin-6 agents, or colchicine therapy within 3 months prior to the baseline visit. o) Previous use of Kiacta. p) History of malignancy within 5 years 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.
Design outcomes
Primary
| Measure | 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)Timepoint: Time Frame: Up to 24 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Estimated glomerular filtration rate (eGFR)Timepoint: Time Frame: screening, baseline, every 3 months, 12 months , early termination, treatment completion, end of study visit;Progression to end-stage renal disease (ESRD)Timepoint: Time Frame: baseline, every 3 months to end of study visit;Rate of change (slope)in Creatinine clearance(CrCL) overtimeTimepoint: Time Frame: baseline to primary endpoint, measured every 3 months to end of study visit;Serum amyloid ATimepoint: Time Frame: baseline, every 3 months, 12 months, early termination, treatment completion, end of study visit;Serum cystatin C over timeTimepoint: Time Frame: 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 mortalityTimepoint: Time Frame: Up to 24 months;Urinary protein/creatinine ratioTimepoint: Time Frame: screening, baseline, every 3 months, 12 months, early termination, treatment completion, end of study visit | — |
Countries
Argentina, Belgium, Brazil, Bulgaria, Chile, Czech Republic, Egypt, Finland, France, Germany, India, Israel, Italy, Lithuania, Mexico, Netherlands, Peru, Poland, Russian Federation, Spain, Sweden, Tunisia, Turkey, Ukraine, United Kingdom, United States of America
Contacts
Public ContactArun Sundriyal
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Outcome results
None listed