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Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)Phase 3NCT05667493

An Extension Study to Assess Long-Term Safety of Eplontersen in Adults With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR-CM)

A Phase 3 study testing Eplontersen in people with Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM), run by Ionis Pharmaceuticals, Inc. at 134 sites in 20 countries.

Enrolling by invitation

Enrolling by invitation. The study team selects and invites participants, usually from an existing group of patients.

Sites and contacts
Official record
Search all trials

Trial summary

The purpose of this study is to evaluate the safety and tolerability of extended dosing with eplontersen in participants with ATTR-CM. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Eplontersen
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,400 participants
Where
134 sitesin 20 countries
Study dates
30 Nov 2022to Aug 2029
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Satisfactory completion of Treatment Period and the End of Treatment Visit of the Index Study (ION-682884-CS2) OR diagnosis of ATTR-CM and satisfactory participation on ISIS 420915- CS101 study as judged by the Investigator and Sponsor.
  • Investigator is willing to treat the participant with open-label eplontersen.
  • Willingness to adhere to vitamin A supplementation per protocol.

Who cannot join

  • Permanently discontinued study drug administration while participating in the Index Study (ION 682884-CS2) or IST (ISIS 420915-CS101 Study).
  • Have any new condition or worsening of an existing condition that in the opinion of the Investigator or Sponsor would make the participant unsuitable for enrolment, or which could interfere with the participant participating in or completing the study, including the need for treatment with medications disallowed in the Index Study.

Trial locations and contacts

134 sites in 20 countries. Contact the study team or a site near you to ask about taking part.

134 sites in 20 countries

United States46 sites

  • Piedmont Heart of Fayetteville

    Atlanta, Georgia, 30309

  • Emory Heart and Vascular Center - Emory Clifton Campus

    Atlanta, Georgia, 30322

  • University of Colorado Hospital - Anschutz Medical Campus

    Aurora, Colorado, 80045

  • University of Maryland Medical Center

    Baltimore, Maryland, 21201

  • Cedars-Sinai Medical Center

    Beverly Hills, California, 90211

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Boston University School of Medicine

    Boston, Massachusetts, 02118

  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27599

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Northwestern University

    Chicago, Illinois, 60611

  • Carl and Edyth Lindner Research Center at The Christ Hospital

    Cincinnati, Ohio, 45219

  • University Hospitals Cleveland Medical Center

    Cleveland, Ohio, 44106

  • Cleveland Clinic Main Campus

    Cleveland, Ohio, 44195

  • The Ohio State University College of Medicine

    Columbus, Ohio, 43210

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • Henry Ford Health System

    Detroit, Michigan, 48202

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Piedmont Atlanta Hospital

    Fayetteville, Georgia, 30214

  • Houston Methodist Hospital

    Houston, Texas, 77030

  • Indiana University Health University Hospital

    Indianapolis, Indiana, 46202

  • University of Kansas Medical Center (KUMC)

    Kansas City, Kansas, 66160

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • Saint Luke's Hospital of Kansas City

    Kansas City, Missouri, 64111

  • Altman Clinical and Translational Research Institute - Center for Clinical Research

    La Jolla, California, 92037

  • Lancaster General Hospital

    Lancaster, Pennsylvania, 17602

  • University of Wisconsin - Madison

    Madison, Wisconsin, 53792

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • Allina Health Minneapolis Heart Institute - Abbott Northwestern's Heart Hospital

    Minneapolis, Minnesota, 55407

  • Vanderbilt Heart and Vascular Institute

    Nashville, Tennessee, 37232

  • New York University Langone Cardiology Associates

    New York, New York, 10016

  • Weill Cornell Medicine Cardiology

    New York, New York, 10021

  • Columbia University Irving Medical Center

    New York, New York, 10034

  • Penn Presbyterian Medical Center

    Philadelphia, Pennsylvania, 19104

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Virginia Commonwealth University

    Richmond, Virginia, 23298

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of Utah

    Salt Lake City, Utah, 84112

  • University Of California San Francisco Urology Practice

    San Francisco, California, 94143

  • Mayo Clinic

    Scottsdale, Arizona, 85259

  • University of Washington

    Seattle, Washington, 98195

  • Barnes-Jewish Hospital

    St Louis, Missouri, 63110

  • Stanford University (Leland Stanford Junior University)

    Stanford, California, 94305

  • MedStar Washington Hospital Center

    Washington D.C., District of Columbia, 20010

  • The George Washington Medical Faculty Associates - Foggy Bottom North Pavilion

    Washington D.C., District of Columbia, 20037

  • Cleveland Clinic Florida

    Weston, Florida, 33331

Other trials in United States

Japan11 sites

  • Saiseikai Fukuoka General Hospital

    Fukuoka, Hukuoka [Fukuoka], 810-0001

  • Saiseikai Fukuoka General Hospital

    Fukuoka, 810-0001

  • Hamamatsu University Hospital

    Hamamatsu, 4313192

  • Kumamoto University Hospital

    Kumamoto, 860-8556

  • Kurume University Hospital

    Kurume, 830-0011

  • Kurume University Hospital

    Kurume-Shi, Fukuoka, 830-0011

  • Shinshu University Hospital

    Matsumoto, 390-8621

  • Okayama University Hospital

    Okayama, 700-8558

  • Osaka Metropolitan University Hospital

    Osaka, 545-8586

  • Sapporo Medical University Hospital

    Sapporo, 060-8543

  • Keio University Hospital

    Shinjuku-Ku, 160-8582

Other trials in Japan

Australia10 sites

  • Box Hill Hospital

    Clayton, 3168

  • Royal Hobart Hospital

    Hobart, 7000

  • Advara HeartCare

    Joondalup, Western Australia, 6027

  • Advara HeartCare - Joondalup

    Joondalup, 6027

  • Advara Heartcare Leabrook

    Leabrook, 5068

  • Liverpool Hospital

    Liverpool, 2170

  • Advara HeartCare Murdoch

    Murdoch, Western Australia, 6150

  • Advara HeartCare Murdoch

    Murdoch, 6150

  • Westmead Hospital

    Westmead, 2145

  • Princess Alexandra Hospital

    Woolloongabba, 4102

Other trials in Australia

United Kingdom8 sites

  • AES - Synexus - Scotland Clinical Research Centre

    Bellshill, England, ML4 3NJ

  • AES - Synexus - Wales

    Cardiff, Wales, CF15 9SS

  • AES - Synexus - Midlands

    Edgbaston, England, B15 2SQ

  • Royal Free London NHS Foundation Trust

    Hampstead, NW3 2PF

  • Synexus - Merseyside Clinical Research Centre

    Liverpool, L22 0LG

  • Richmond Pharmacology

    London, SE1 1YR

  • Synexus - Manchester Clinical Research Centre

    Manchester, England, M15 6SE

  • Synexus - Merseyside Clinical Research Centre

    Manchester, M15 6SE

Other trials in United Kingdom

Brazil7 sites

  • Hospital Moinhos de Vento

    Porto Alegre, 90560-030

  • Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto

    Ribeirão Preto, 14040-030

  • A Beneficência Portuguesa de São Paulo - Unidade Mirante

    São Paulo, 01323-030

  • Instituto Dante Pazzanese de Cardiologia

    São Paulo, 04012-909

  • Instituto do Coração de São Paulo

    São Paulo, 05403-000

  • Universidade Estadual de Campinas

    São Paulo, 13083881

  • Centro Avançado de Pesquisa e Estudos para o Diagnóstico CAPED

    São Paulo, 14026-900

Other trials in Brazil

Portugal7 sites

  • Hospital da Senhora da Oliveira

    Guimarães, 4835-044

  • Unidade Local de Saúde do Alto Ave, E. P. E (Hospital da Senhora da Oliveira Guimarães)

    Guimarães, 4835-044

  • Unidade Local de Saúde de São José, E. P. E - Hospital de Santa Marta

    Lisbon, 1169-024

  • Centro Hospitalar Universitário do Porto - Hospital Geral de Santo Antonio

    Porto, 4099-001

  • Unidade Local de Saúde de Santo António, E. P. E - Hospital Geral de Santo Antonio

    Porto, 4099-001

  • Centro Hospitalar Universitário de São João

    Porto, 4200-319

  • Unidade Local de Saúde de São João, EPE

    Porto, 4200-319

Other trials in Portugal

Canada6 sites

  • University of Calgary

    Calgary, Alberta, T2N 4Z6

  • University Hospital - London Health Sciences Centre

    London, Ontario, N6A 5A5

  • Centre Hospitalier de l'Université de Montréal (CHUM)

    Montreal, Quebec, H2X 0C1

  • Hôpital Regional de Rimouski

    Rimouski, G5L 5T1

  • Toronto General Hospital

    Toronto, Ontario, M5G 2C4

  • Gordon and Leslie Diamond Health Care Centre

    Vancouver, V5Z 1M9

Other trials in Canada

France6 sites

  • Hôpitaux Universitaires Henri Mondor

    Créteil, 94010

  • Centre Hospitalier Départemental Vendée

    La Roche-sur-Yon, 85925

  • Hôpital de la Timone

    Marseille, 13005

  • Centre Hospitalier Universitaire De Nantes - Hôpital Nord Laennec

    Nantes, 44093

  • Hôpital Haut-Lévêque

    Pessac, 33604

  • Hôpital Rangueil

    Toulouse, 31059

Other trials in France

Italy6 sites

  • Azienda Ospedaliero Universitaria Delle Marche

    Ancona, 60126

  • Azienda Ospedaliero - Universitaria Careggi

    Florence, 50134

  • Azienda Ospedale Università di Padova

    Padova, 35128

  • Fondazione IRCCS Policlinico San Matteo

    Pavia, 27100

  • Fondazione Toscana Gabriele Monasterio per la Ricerca Medica e di Sanita Pubblica

    Pisa, 56124

  • Azienda Ospedaliera - Universitaria Sant' Andrea

    Roma, 00189

Other trials in Italy

Germany5 sites

  • Uniklinik Köln

    Cologne, 50937

  • Universitaetsklinikum Heidelberg - Zentrum für Innere Medizin

    Heidelberg, 69120

  • Universitätsklinikum des Saarlandes

    Homburg, 66421

  • Universitätsklinikum Münster

    Münster, 48149

  • Universitätsklinikum Würzburg

    Würzburg, 97078

Other trials in Germany

Spain4 sites

  • Hospital Universitari Vall d'Hebrón

    Barcelona, 08035

  • Hospital Universitario Puerta de Hierro

    Majadahonda, 28222

  • Hospital Clínico Universitario Virgen de la Arrixaca

    Murcia, 30120

  • Complejo Hospitalario Universitario de Santiago (CHUS)

    Santiago de Compostela, 15706

Other trials in Spain

Austria3 sites

  • Medizinische Universität Graz

    Graz, 8036

  • Medizinische Universität Innsbruck

    Innsbruck, 6020

  • Medizinische Universität Wien

    Vienna, 1090

Other trials in Austria

Czechia3 sites

  • Fakultní Nemocnice u sv. Anny v Brně

    Brno, 656 91

  • Vseobecna Fakultni Nemocnice v Praze

    Prague, 116 36

  • Institut Klinické a Experimentální Medicíny

    Prague, 140 21

Other trials in Czechia

Israel3 sites

  • Rambam Health Care Campus

    Haifa, 3109601

  • Hadassah University Hospital Ein Kerem

    Jerusalem, 9112001

  • Kaplan Medical Center

    Rehovot, 7661041

Other trials in Israel

Argentina2 sites

  • Hospital Italiano de Buenos Aires

    Buenos Aires, C1199ABB

  • Instituto Cardiovascular de Buenos Aires

    Buenos Aires, C1428ART

Other trials in Argentina

Belgium2 sites

  • Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan

    Bruges, 8000

  • Ziekenhuis Oost-Limburg - Campus Sint-Jan

    Limbourg, 3600

Other trials in Belgium

Sweden2 sites

  • Sahlgrenska Universitetssjukhuset

    Gothenburg, 413 45

  • Skellefteå lasarett

    Skellefteå, 931 86

Other trials in Sweden

Denmark1 site

  • Rigshospitalet

    Copenhagen, 2100

Other trials in Denmark

Greece1 site

  • General Hospital of Athens "Alexandra"

    Athens, 115 28

Other trials in Greece

Poland1 site

  • Krakowski Szpital Specjalistyczny im. Jana Pawła II

    Krakow, 31- 202

Other trials in Poland

About this study

Official title: An Open-Label Extension Study to Assess the Long-Term Safety of Eplontersen (ION-682884) in Patients With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR-CM)

The purpose of this study is to evaluate the safety and tolerability of extended dosing with eplontersen in participants with ATTR-CM.

Read the detailed description

This is a multicenter, open-label extension, Phase 3 study in up to approximately 1400 participants from the 682884-CS2 study. Eligible participants will receive eplontersen once every 4 weeks for up to 36 months or until after eplontersen is approved and available in the site's country, whichever occurs first. Participants will also receive daily supplemental doses of the recommended daily allowance (RDA) of vitamin A.

Being tested
Eplontersen
Keywords
Amyloidosis
Medical subject headings
Amyloidosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EplontersenDrug

    Also called ION-682884, IONIS-TTR-LRx

    Eplontersen will be administered by SC injection.

Study groups in NCT05667493
Study groupRoleWhat they receive
EplontersenExperimentalEplontersen will be administered once every month by sub-cutaneous (SC) injection for up to 36 months or 6 months after eplontersen is approved and available in the site's country, whichever occurs first.
Receives: Drug: Eplontersen

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)

    Measured: Baseline up to 36 months

  2. Change From Baseline in Platelet Count

    Measured: Baseline up to 36 months

  3. Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)

    Measured: Baseline up to 36 months

  4. Change From Baseline in Urine Protein Creatinine Ratio (UPCR)

    Measured: Baseline up to 36 months

Secondary outcomes (3)

  1. Change From Baseline in Transthyretin (TTR) Serum Levels

    Measured: Baseline up to 36 months

  2. Change From Baseline in 6-minute Walk Test (6MWT)

    Measured: Baseline up to 36 months

  3. Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ)

    Measured: Baseline up to 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Dec 2022
  2. Study start30 Nov 2022
  3. Primary completionAug 2029 (estimated)
  4. Study completionAug 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
1,400 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05667493
Sponsor's protocol ID
ION-682884-CS12
Other IDs
2022-000826-74
Status last verified
Apr 2026
First submitted
12 Jul 2022
Last updated
17 Apr 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Ionis may share anonymized individual participant data, aggregated clinical data, and other types of data that support the results in this study. Data requests from qualified researchers will be considered once all three of the following criteria are met: (1) 12 months from marketing approval of the study drug in both the United States and European Union; (2) 18 months from conclusion of the study; and (3) 6 months from publication of study article. Access would be via a secure environment and is contingent upon approval of a research proposal and entry into an appropriate data use agreement. Requests to access data can be submitted via the website https://vivli.org/ourmember/ionis/.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Eplontersen in people with Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM), run by Ionis Pharmaceuticals, Inc. at 134 sites in 20 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: enrolling by invitation, as of the sponsor's last update on 17 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 134 sites in United States, Japan, Australia, United Kingdom, Brazil and 15 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) (time frame: Baseline up to 36 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05667493.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2026; AzTrials last refreshed its copy on 26 Oct 2026.

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