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

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

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

Study Overview

• Status: Completed
• Conditions: Amyloidosis
• Intervention / Treatment: Drug: KIACTA (eprodisate disodium); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 261
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven
• Egypt
  • Cairo, Egypt, 11214
    • Al Hussain University Hospital
• Estonia
  • Tartu, Estonia, EE-51014
    • Tartu University Hospital
• Finland
  • Helsinki, Finland, FI-00290
    • Helsingin yliopistollinen keskussairaala / Meilahti
• France
  • Creteil, France, 94010
    • Hopital Henri Mondor
  • Lille, France, 59037
    • Hopital Claude Huriez
• Georgia
  • Tbilisi, Georgia, 0159
    • Tbilisi Heart and Vascular Clinic Ltd
• Germany
  • Heidelberg, Germany, 69120
    • Universität Heidelberg
• India
  • Kanpur, India, 208005
    • Regency Hospital
  • Nadiad, India, 387001
    • Muljibhai Patel Urological Hospital
  • New Delhi, India, 110060
    • Sir Ganga Ram Hospital
• Israel
  • Haifa, Israel, 31048
    • Bnei Zion Medical Center
  • Ramat-Gan, Israel, 52621
    • The Chaim Sheba Medical Center
• Italy
  • Pavia, Italy, 27100
    • IRCCS Policlinico San Matteo
• Latvia
  • Riga, Latvia, LV-1002
    • Pauls Stradins Clinical University Hospital
• Lithuania
  • Kaunas, Lithuania, LT-50009
    • Hospital of Lithuanian University of Health Sciences Kaunas Clinics
  • Vilnius, Lithuania, LT-08661
    • Vilnius University Hospital Santariskiu Klinikos
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Universitair Medisch Centrum Groningen
  • Maastricht, Netherlands, 6229 HX
    • Academisch Ziekenhuis Maastricht
• Peru
  • Lima, Peru, Lima 1
    • Hospital Nacional Arzobispo Loayza
• Poland
  • Olsztyn, Poland, 10-561
    • Wojewodzki Szpital Specjalistyczny
  • Warszawa, Poland, 02-653
    • ARS RHEUMATICA Sp. z o.o.
  • Wroclaw, Poland, 50-556
    • Akademicki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu
• Russian Federation
  • Ekaterinburg, Russian Federation, 620102
    • Sverdlovsk Regional Clinical Hospital #1
  • Kemerovo, Russian Federation, 650066
    • Kemerovo State Medical Academy of Roszdrav
  • Moscow, Russian Federation, 115522
    • Institute of Rheumatology of RAMN
  • Novosibirsk, Russian Federation, 630117
    • Research Institute of Clinical and Experimental Lymphology
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic de Barcelona
  • Malaga, Spain, 29009
    • Hospital Civil Carlos Haya
• Sweden
  • Stockholm, Sweden, SE-14186
    • Karolinska Universitetssjukhuset i Huddinge
• Tunisia
  • Monastir, Tunisia, 5000
    • Fattouma Bourguiba University Hospital
  • Sfax, Tunisia, 3029
    • Hédi Chaker University Hospital
  • Sousse, Tunisia, 4020
    • Sahloul Hospital
  • Tunis, Tunisia, 1007
    • La Rabta Hospital
  • Tunis, Tunisia, 1006
    • Hopital Charles Nicolle
• Turkey
  • Adana, Turkey, 01330
    • Cukurova University Medical Faculty Balcali Hospital
  • Ankara, Turkey, 06100
    • Hacettepe University Medical Faculty
  • Eskisehir, Turkey, 26480
    • Eskisehir Osmangazi University Medical Faculty
• Ukraine
  • Donetsk, Ukraine, 83003
    • Municipal Medical & Preventive Institution Donetsk Regional Clinical Territorial Medical Association
  • Kyiv, Ukraine, 03680
    • National Scientific Center "Institute of cardiology n.a. academician M.D Strazhesko"
  • Kyiv, Ukraine, 04050
    • State Institution "Institute of Nephrology of AMS of Ukraine"
  • Kyiv, Ukraine, 2125
    • State Institution "Institute of Nephrology of AMS of Ukraine"
• United Kingdom
  • London, United Kingdom, NW3 2PF
    • Royal Free Hospital
• United States
  • California
    • Glendale, California, United States, 91204
      • Raffi Minasian MD a Medical Corporation
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	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)	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.

What is the study measuring?

Primary Outcome Measures

Outcome 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)	Up to 24 months

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: C.T. Development America, Inc.
• Investigators: Study Director: Tomasz Sablinski, MD, PhD, CT Development America, Inc.

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: October 1, 2010
• First Submitted That Met QC Criteria: October 5, 2010
• First Posted (Estimate): October 6, 2010

Study Record Updates

• Last Update Posted (Estimate): March 10, 2016
• Last Update Submitted That Met QC Criteria: March 9, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Kiacta for AA amyloidosis
• Additional Relevant MeSH Terms: Metabolic Diseases; Proteostasis Deficiencies; Amyloidosis
• Other Study ID Numbers: CL-503012