CARDIO-TTRansform: A Study to Evaluate the Efficacy and Safety of Eplontersen (Formerly Known as ION-682884, IONIS-TTR-LRx and AKCEA-TTR-LRx) in Participants With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)

January 20, 2024 updated by: Ionis Pharmaceuticals, Inc.

A Phase 3 Global, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of ION-682884 in Patients With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)

To evaluate the efficacy of eplontersen compared to placebo in participants with ATTR-CM receiving available standard of care (SoC). For more information, please visit https://www.cardio-ttransform.com.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a multicenter, double-blind study in approximately 1400 participants, who will be randomized to receive subcutaneous (SC) injections of either eplontersen or placebo once every 4 weeks. Participants will also receive daily supplemental doses of the recommended daily allowance of vitamin A.

Study Type

Interventional

Enrollment (Actual)

1438

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Argentina
    • Buenos Aires
      • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1428ART
        • Instituto Cardiovascular de Buenos Aires
      • Ciudad Autónoma De Buenos Aires, Buenos Aires, Argentina, C1199ABB
        • Hospital Italiano de Buenos Aires
  • Australia
    • New South Wales
      • Liverpool, New South Wales, Australia, 2170
        • Liverpool Hospital
      • Westmead, New South Wales, Australia, NSW 2145
        • The Westmead Institute for Medical Research
    • Queensland
      • Woolloongabba, Queensland, Australia, 4102
        • Princess Alexandra Hospital
    • South Australia
      • Leabrook, South Australia, Australia, 5068
        • Advara HeartCare
    • Tasmania
      • Hobart, Tasmania, Australia, 7000
        • Royal Hobart Hospital
    • Victoria
      • Box Hill, Victoria, Australia, 3128
        • Box Hill Hospital
    • West Australia
      • Murdoch, West Australia, Australia, 6150
        • Advara HeartCare Murdoch
      • Murdoch, West Australia, Australia, 6150
        • GenesisCare Murdoch
    • Western Australia
      • Joondalup, Western Australia, Australia, 6027
        • Advara HeartCare
      • Joondalup, Western Australia, Australia, 6027
        • GenesisCare Joondalup
  • Austria
      • Vienna, Austria, 1090
        • Medizinische Universität Wien
    • Styria
      • Graz, Styria, Austria, 8036
        • Medizinische Universität Graz
    • Tyrol
      • Innsbruck, Tyrol, Austria, 6020
        • Medizinische Universität Innsbruck
  • Belgium
    • Limburg
      • Genk, Limburg, Belgium, 3600
        • Ziekenhuis Oost-Limburg - Campus Sint-Jan
    • West-Vlaanderen
      • Brugge, West-Vlaanderen, Belgium, 8000
        • Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan
  • Brazil
      • Campinas, Brazil, 13083881
        • Universidade Estadual de Campinas
      • Porto Alegre, Brazil, 90560-030
        • Hospital Moinhos de Vento
      • Ribeirão Preto, Brazil, 14026-900
        • Centro Avançado de Pesquisa e Estudos para o Diagnóstico CAPED
      • Ribeirão Preto, Brazil, 14040-030
        • Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto
      • São Paulo, Brazil, 04012-909
        • Instituto Dante Pazzanese de Cardiologia
      • São Paulo, Brazil, 01323-030
        • A Beneficência Portuguesa de São Paulo - Unidade Mirante
      • São Paulo, Brazil, 05403-000
        • Instituto do Coração de São Paulo
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4Z6
        • University of Calgary
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 1M9
        • Gordon and Leslie Diamond Health Care Centre
    • Ontario
      • London, Ontario, Canada, N6A 5A5
        • University Hospital - London Health Sciences Centre
      • Toronto, Ontario, Canada, M5G 2M9
        • Toronto General Hospital
    • Quebec
      • Montréal, Quebec, Canada, H2X 0C1
        • Centre hospitalier de l'Université de Montréal (CHUM)
      • Rimouski, Quebec, Canada, G5L 5T1
        • Hôpital Regional de Rimouski
  • Czechia
      • Prague, Czechia, 128 08
        • Vseobecna fakultni nemocnice v Praze
      • Prague, Czechia, 140 21
        • Institut Klinicke A Experimentalni Mediciny
    • South Moravian
      • Brno, South Moravian, Czechia, 656 91
        • Fakultní Nemocnice u sv. Anny v Brn
  • Denmark
    • Hovedstaden
      • Copenhagen, Hovedstaden, Denmark, 2100
        • Rigshospitalet
    • Syddanmark
      • Odense, Syddanmark, Denmark, 5000
        • Odense Universitetshospital
  • France
      • Créteil, France, 94010
        • Hôpitaux Universitaires Henri Mondor
      • La Roche-sur-Yon, France, 85925
        • Centre Hospitalier Departemental Vendée
      • Marseille, France, 13005
        • Hôpital de la Timone
      • Pessac, France, 33604
        • Hôpital Haut-Lévêque
      • Saint-Herblain, France, 44805
        • Centre Hospitalier Universitaire De Nantes - Hôpital Nord Laennec
    • Occitanie
      • Toulouse, Occitanie, France, 31059
        • Hôpital Rangueil
  • Germany
      • Berlin, Germany, 13353
        • Charité Universitätsmedizin Berlin
      • Berlin, Germany, 10117
        • Charité Campus Mitte
      • Heidelberg, Germany, 69120
        • Universitaetsklinikum Heidelberg - Zentrum fur Innere Medizin
      • Köln, Germany, 50937
        • Uniklinik Koln
      • Münster, Germany, 48149
        • Universitatsklinikum Munster
      • Würzburg, Germany, 97078
        • Universitätsklinikum Würzburg
    • Saarland
      • Homburg, Saarland, Germany, 66421
        • Universitätsklinikum des Saarlandes
  • Greece
      • Athens, Greece, 11528
        • Alexandra General Hospital
  • Israel
      • Haifa, Israel, 3109601
        • Rambam Health Care Campus
      • Jerusalem, Israel, 9112001
        • Hadassah University Hospital Ein Kerem
      • Rehovot, Israel
        • Kaplan Medical Center
  • Italy
      • Ancona, Italy, 60126
        • Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona
      • Bologna, Italy, 40138
        • Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant Orsola-Malpighi
      • Florence, Italy, 50139
        • Azienda Ospedaliero - Universitaria Careggi
      • Padua, Italy, 35128
        • Azienda Ospedale - Università di Padova
      • Pavia, Italy, 27100
        • Fondazione IRCCS Policlinico San Matteo
      • Pisa, Italy, 56126
        • Fondazione Toscana Gabriele Monasterio per la Ricerca Medica e di Sanita Pubblica
      • Roma, Italy, 00189
        • Azienda Ospedaliera - Universitaria Sant' Andrea
  • Japan
      • Kumamoto, Japan, 860-8556
        • Kumamoto University Hospital
    • Ehime
      • Uwajima-shi, Ehime, Japan, 798-8510
        • Uwajima City Hospital
    • Fukuoka
      • Kitakyushu-shi, Fukuoka, Japan, 807-8555
        • Hospital of the university of occupational and environmental health
      • Kurume-shi, Fukuoka, Japan, 830-0011
        • Kurume University Hospital
    • Hokkaido
      • Sapporo-shi, Hokkaido, Japan, 060-8543
        • Sapporo Medical University Hospital
    • Hukuoka
      • Fukuoka, Hukuoka, Japan, 810-0001
        • Saiseikai Fukuoka General Hospital
      • Kitakyushu, Hukuoka, Japan, 802-8555
        • Kokura Memorial Hospital
    • Kyoto
      • Kyoto-shi, Kyoto, Japan, 602-8566
        • University Hospital Kyoto Prefectural University of Medicine
    • Nagano
      • Matsumoto, Nagano, Japan, 390-8621
        • Shinshu University Hospital
    • Okayama
      • Okayama-shi,, Okayama, Japan, 700-8558
        • Okayama University Hospital
    • Osaka
      • Osaka-shi, Osaka, Japan, 545-8586
        • Osaka Metropolitan University Hospital
    • Shizuoka
      • Hamamatsu, Shizuoka, Japan, 431-3192
        • Hamamatsu University Hospital
    • Tokyo
      • Shinjuku-Ku, Tokyo, Japan, 160-8582
        • Keio University Hospital
  • Poland
      • Kraków, Poland, 31-202
        • Krakowski Szpital Specjalistyczny im. Jana Pawa II
      • Warszawa, Poland, 04-628
        • Narodowy Instytut Kardiologii Stefana kardyna Wyszyskiego - Pastwowy Instytut Badawczy
  • Portugal
      • Guimarães, Portugal, 4835-044
        • Hospital da Senhora da Oliveira - Guimarães
      • Lisbon, Portugal, 1169-024
        • Centro Hospitalar Universitário de Lisboa Central - Hospital de Santa Marta
      • Porto, Portugal, 4099-001
        • Centro Hospitalar Universitario do Porto - Hospital Geral de Santo Antonio
      • Porto, Portugal, 4200-319
        • Centro Hospitalar Universitário de São João
  • Puerto Rico
      • San Juan, Puerto Rico, 00921
        • Veterans Affairs Caribbean Healthcare System
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron
      • Majadahonda, Spain, 28222
        • Hospital Universitario Puerta de Hierro - Majadahonda
      • Murcia, Spain, 30120
        • Hospital Clínico Universitario Virgen de la Arrixaca
      • Santiago de Compostela, Spain, 15706
        • Complejo Hospitalario Universitario de Santiago
  • Sweden
      • Göteborg, Sweden, 413 45
        • Sahlgrenska Universitetssjukhuset
      • Skellefteå, Sweden, 931 86
        • Skellefteå lasarett
  • United Kingdom
      • Edgbaston, United Kingdom, B15 2SQ
        • Synexus Midlands Clinical Research Centre
      • Hexham, United Kingdom, TS19 8PE
        • Synexus - North Tees Clinical Research Centre
      • Liverpool, United Kingdom, L22 0LG
        • Synexus - Merseyside Clinical Research Centre
      • Liverpool, United Kingdom, L22 0LG
        • Synexus - Manchester Clinical Research Centre
      • London, United Kingdom, SE1 1YR
        • Richmond Pharmacology
      • London, United Kingdom, HR3M+6R
        • Royal Free London NHS Foundation Trust
    • Scotland
      • Glasgow, Scotland, United Kingdom, G20 0SP
        • Synexus - Scotland Clinical Research Centre
    • Wales
      • Cardiff, Wales, United Kingdom, CF15 9SS
        • Synexus - Wales
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic - Arizona
    • California
      • La Jolla, California, United States, 92037
        • Altman Clinical and Translational Research Institute Center for Clinical Research
      • Los Angeles, California, United States, 90048
        • Cedars-Sinai Medical Center
      • San Francisco, California, United States, 94143
        • University of California, San Francisco (UCSF) - Medical Center
      • Stanford, California, United States, 94305
        • Stanford hospital
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Hospital - Anschutz Medical Campus
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • MedStar Washington Hospital Center
      • Washington, District of Columbia, United States, 20037
        • The George Washington Medical Faculty Associates - Foggy Bottom North Pavilion
    • Florida
      • Weston, Florida, United States, 33331
        • Cleveland Clinic Florida
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory Heart and Vascular Center - Emory Clifton Campus
      • Fayetteville, Georgia, United States, 30214
        • Piedmont Heart of Fayetteville
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Chicago, Illinois, United States, 60637
        • The University of Chicago Medical Center
      • Maywood, Illinois, United States, 60153
        • Loyola University Medical Center
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Health
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Medical Center
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Health System
      • New Orleans, Louisiana, United States, 70112
        • Louisiana State University Health Sciences Center
      • New Orleans, Louisiana, United States, 70112
        • Tulane University Heart and Vascular Institute
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02118
        • Boston University School of Medicine
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Health System
    • Minnesota
      • Minneapolis, Minnesota, United States, 55407
        • Minneapolis Heart Institute
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic - Rochester
    • Missouri
      • Kansas City, Missouri, United States, 64111
        • Saint Luke'S Hospital of Kansas City
      • Saint Louis, Missouri, United States, 63110
        • Barnes-Jewish Hospital
    • New York
      • New York, New York, United States, 10034
        • Columbia University Irving Medical Center
      • New York, New York, United States, 10016
        • New York University Langone Cardiology Associates
      • New York, New York, United States, 10065
        • Weill Cornell Medicine Cardiology
      • Rosedale, New York, United States, 11422
        • Laurelton Heart Specialists
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • The University of North Carolina at Chapel Hill
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Carl and Edyth Lindner Research Center at The Christ Hospital
      • Cleveland, Ohio, United States, 44106
        • University Hospitals Cleveland Medical Center
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Main Campus
      • Columbus, Ohio, United States, 43210
        • The Ohio State University College of Medicine
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
    • Pennsylvania
      • Lancaster, Pennsylvania, United States, 17602
        • Lancaster General Hospital
      • Philadelphia, Pennsylvania, United States, 19104
        • Penn Presbyterian Medical Center
      • Pittsburgh, Pennsylvania, United States, 15261
        • University of Pittsburgh Medical School
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern Medical Center
      • Houston, Texas, United States, 77030
        • Houston Methodist Hospital
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • University of Utah
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University (VCU)
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin - Madison
      • Milwaukee, Wisconsin, United States, 53226
        • Froedtert & Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal or abstinent. If engaged in sexual relations of child-bearing potential, agree to use 1 highly effective contraceptive method
  • Males must be surgically sterile or, abstinent or, if engaged in sexual relations with a woman of child-bearing potential, the participant or the participant's non-pregnant female partner must be using a highly effective contraceptive method
  • Amyloid deposits in cardiac or non-cardiac tissue confirmed by Congo Red (or equivalent) staining OR technetium scintigraphy (99mTc -3,3-diphosphono-1,2- propanodicarboxylic acid [DPD-Tc], 99m Tc-pyrophosphate [PYP-Tc], or 99m Tc-hydroxymethylene-diphosphonate [HMDP-Tc]) with Grade 2 or 3 cardiac uptake in the absence of abnormal light chains ratio, centrally confirmed
  • End-diastolic interventricular septum thickness of > 12 millimeters (mm) on Screening echocardiogram
  • New York Heart Association (NYHA) class I-III

Exclusion Criteria:

  • Acute coronary syndrome, unstable angina, stroke, transient ischemic attack (TIA), coronary revascularization, cardiac device implantation, cardiac valve repair, or major surgery within 3 months of Screening
  • Cardiomyopathy not primarily caused by ATTR-CM, for example, cardiomyopathy due to hypertension, valvular heart disease, or ischemic heart disease
  • Monoclonal gammopathy of undetermined significance (MGUS) and/or alterations in immunoglobulin free light chain (FLC) ratio unless fat, bone marrow, or heart biopsy confirming the absence of light chain and the presence of TTR protein by mass spectrometry or immunoelectron microscopy. For participants with chronic kidney disease (CKD) and without presence of monoclonal protein in blood and urine, the acceptable FLC ratio is 0.26-2.25. Results different from that may be discussed with local hematologist, Investigator and Medical Monitor if the risks associated with the biopsy outweigh the benefits
  • Prior liver or heart transplant, and/or Left Ventricular Assist Device (LVAD) or anticipated liver transplant or LVAD within 1 year after randomization
  • Current or previous treatment with Tegsedi™ (inotersen) or Onpattro™ (patisiran) or other oligonucleotide or ribonucleic acid (RNA) therapeutic (including small interfering ribonucleic acid [siRNA]; does not apply to COVID-19 mitochondrial [mRNA] vaccinations)
  • Current treatment with diflunisal, doxycycline, with or without ursodeoxycholic acid, and/or non-dihydropyridine calcium-channel blocker (e.g., verapamil, diltiazem). Participants receiving any of these agents must respect a wash-out period of 14 days before randomization.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Eplontersen
Eplontersen by subcutaneous injection once every 4 weeks
Drug: Eplontersen
Eplontersen by subcutaneous injection
Other Names:
  • ION-682884
  • AKCEA-TTR-LRx
  • IONIS-TTR-LRx
Placebo Comparator: Placebo
Eplontersen-matching placebo by subcutaneous injection once every 4 weeks
Drug: Placebo
Eplontersen-matching placebo by subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Composite Outcome of Cardiovascular (CV) Mortality and Recurrent CV Clinical Events up to Week 140
Time Frame: Baseline up to Week 140
Baseline up to Week 140

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in the 6-minute Walk Test (6MWT) Distance at Week 121
Time Frame: Baseline to Week 121
The 6MWT is a submaximal exercise test that entails measurement of distance walked over a span of 6 minutes. The 6MWT provides information regarding functional capacity, response to therapy and prognosis across a range of chronic cardiopulmonary conditions.
Baseline to Week 121
Change From Baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Week 121
Time Frame: Baseline to Week 121

The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a 23-item self-administered questionnaire developed to independently measure the participant's perception of their health status, which includes heart failure symptoms, impact on physical and social function, and how their heart failure impacts their quality of life (QOL) within a 2-week recall period.

The KCCQ tool quantifies the following six (6) distinct domains and two (2) summary scores. KCCQ responses are provided along a rating scale continuum with equal spacing from worst to best, with a higher score equaling a better score.
Baseline to Week 121
CV Clinical Events up to Week 140
Time Frame: Baseline up to Week 140
Baseline up to Week 140
CV Mortality up to Week 140
Time Frame: Baseline up to Week 140
Baseline up to Week 140
All-Cause Mortality up to Week 140
Time Frame: Baseline up to Week 140
Baseline up to Week 140

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ionis Pharmaceuticals, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 13, 2020

Primary Completion (Estimated)

June 1, 2025

Study Completion (Estimated)

November 1, 2025

Study Registration Dates

First Submitted

October 21, 2019

First Submitted That Met QC Criteria

October 21, 2019

First Posted (Actual)

October 23, 2019

Study Record Updates

Last Update Posted (Estimated)

January 23, 2024

Last Update Submitted That Met QC Criteria

January 20, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ION-682884-CS2
  • 2019-002835-27 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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