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

Amyloidosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01215747
• Other study ID #: CL-503012
• Status: Completed
• Phase: Phase 3
• First received: October 1, 2010
• Last updated: March 9, 2016
• Start date: November 2010
• Est. completion date: March 2016

Study information

• Verified date: March 2016
• Source: C.T. Development America, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 261
• Est. completion date: March 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Amyloidosis

Intervention

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.
• Placebo
Orally 1 to 3 capsules (placebo) twice daily and adjusted as per the Creatine Clearance (CrCl) level increases or decreases:

Locations

Country	Name	City	State
Belgium	UZ Leuven	Leuven
Egypt	Al Hussain University Hospital	Cairo
Estonia	Tartu University Hospital	Tartu
Finland	Helsingin yliopistollinen keskussairaala / Meilahti	Helsinki
France	Hôpital Henri Mondor	Creteil
France	Hôpital Claude Huriez	Lille
Georgia	Tbilisi Heart and Vascular Clinic Ltd	Tbilisi
Germany	Universität Heidelberg	Heidelberg
India	Regency Hospital	Kanpur
India	Muljibhai Patel Urological Hospital	Nadiad
India	Sir Ganga Ram Hospital	New Delhi
Israel	Bnei Zion Medical Center	Haifa
Israel	The Chaim Sheba Medical Center	Ramat-Gan
Italy	IRCCS Policlinico San Matteo	Pavia
Latvia	Pauls Stradins Clinical University Hospital	Riga
Lithuania	Hospital of Lithuanian University of Health Sciences Kaunas Clinics	Kaunas
Lithuania	Vilnius University Hospital Santariskiu Klinikos	Vilnius
Netherlands	Universitair Medisch Centrum Groningen	Groningen
Netherlands	Academisch Ziekenhuis Maastricht	Maastricht
Peru	Hospital Nacional Arzobispo Loayza	Lima
Poland	Wojewodzki Szpital Specjalistyczny	Olsztyn
Poland	ARS RHEUMATICA Sp. z o.o.	Warszawa
Poland	Akademicki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu	Wroclaw
Russian Federation	Sverdlovsk Regional Clinical Hospital #1	Ekaterinburg
Russian Federation	Kemerovo State Medical Academy of Roszdrav	Kemerovo
Russian Federation	Institute of Rheumatology of RAMN	Moscow
Russian Federation	Research Institute of Clinical and Experimental Lymphology	Novosibirsk
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Civil Carlos Haya	Malaga
Sweden	Karolinska Universitetssjukhuset i Huddinge	Stockholm
Tunisia	Fattouma Bourguiba University Hospital	Monastir
Tunisia	Hedi Chaker University Hospital	Sfax
Tunisia	Sahloul Hospital	Sousse
Tunisia	Hôpital Charles Nicolle	Tunis
Tunisia	La Rabta Hospital	Tunis
Turkey	Cukurova University Medical Faculty Balcali Hospital	Adana
Turkey	Hacettepe University Medical Faculty	Ankara
Turkey	Eskisehir Osmangazi University Medical Faculty	Eskisehir
Ukraine	Municipal Medical & Preventive Institution Donetsk Regional Clinical Territorial Medical Association	Donetsk
Ukraine	National Scientific Center "Institute of cardiology n.a. academician M.D Strazhesko"	Kyiv
Ukraine	State Institution "Institute of Nephrology of AMS of Ukraine"	Kyiv
Ukraine	State Institution "Institute of Nephrology of AMS of Ukraine"	Kyiv
United Kingdom	Royal Free Hospital	London
United States	Boston Medical Center	Boston	Massachusetts
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Raffi Minasian MD a Medical Corporation	Glendale	California

Sponsors (1)

Lead Sponsor	Collaborator
C.T. Development America, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Egypt,  Estonia,  Finland,  France,  Georgia,  Germany,  India,  Israel,  Italy,  Latvia,  Lithuania,  Netherlands,  Peru,  Poland,  Russian Federation,  Spain,  Sweden,  Tunisia,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	rate of change (slope) in creatinine clearance (CrCL) over time		baseline to primary endpoint, measured every 3 months to end of study visit	No
Secondary	Progression to end-stage renal disease (ESRD)		baseline, every 3 months to end of study visit	No
Secondary	estimated glomerular filtration rate (eGFR)		screening, baseline, every 3 months, 12 months , early termination, treatment completion, end of study visit	No
Secondary	serum cystatin C over time		baseline, every 3 months, 12 months, early termination, treatment completion, end of study visit	No
Secondary	urinary protein/creatinine ratio		screening, baseline, every 3 months, 12 months, early termination, treatment completion, end of study visit	No
Secondary	serum amyloid A		baseline, every 3 months, 12 months, early termination, treatment completion, end of study visit	No
Secondary	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	No