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

April 16, 2026 updated by: Ionis Pharmaceuticals, Inc.

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.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

1400

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 Locations

  • Argentina
      • Buenos Aires, Argentina, C1199ABB
        • Hospital Italiano de Buenos Aires
      • Buenos Aires, Argentina, C1428ART
        • Instituto Cardiovascular de Buenos Aires
  • Australia
      • Clayton, Australia, 3168
        • Box Hill Hospital
      • Hobart, Australia, 7000
        • Royal Hobart Hospital
      • Joondalup, Australia, 6027
        • Advara HeartCare - Joondalup
      • Leabrook, Australia, 5068
        • Advara HeartCare Leabrook
      • Liverpool, Australia, 2170
        • Liverpool Hospital
      • Murdoch, Australia, 6150
        • Advara HeartCare Murdoch
      • Westmead, Australia, 2145
        • Westmead Hospital
      • Woolloongabba, Australia, 4102
        • Princess Alexandra Hospital
    • Western Australia
      • Joondalup, Western Australia, Australia, 6027
        • Advara HeartCare
      • Murdoch, Western Australia, Australia, 6150
        • Advara HeartCare Murdoch
  • Austria
      • Graz, Austria, 8036
        • Medizinische Universität Graz
      • Innsbruck, Austria, 6020
        • Medizinische Universität Innsbruck
      • Vienna, Austria, 1090
        • Medizinische Universität Wien
  • Belgium
      • Bruges, Belgium, 8000
        • Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan
      • Limbourg, Belgium, 3600
        • Ziekenhuis Oost-Limburg - Campus Sint-Jan
  • Brazil
      • Porto Alegre, Brazil, 90560-030
        • Hospital Moinhos de Vento
      • 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
      • São Paulo, Brazil, 13083881
        • Universidade Estadual De Campinas
      • São Paulo, Brazil, 14026-900
        • Centro Avançado de Pesquisa e Estudos para o Diagnóstico CAPED
  • Canada
      • Rimouski, Canada, G5L 5T1
        • Hôpital Regional de Rimouski
      • Vancouver, Canada, V5Z 1M9
        • Gordon and Leslie Diamond Health Care Centre
    • Alberta
      • Calgary, Alberta, Canada, T2N 4Z6
        • University of Calgary
    • Ontario
      • London, Ontario, Canada, N6A 5A5
        • University Hospital - London Health Sciences Centre
      • Toronto, Ontario, Canada, M5G 2C4
        • Toronto General Hospital
    • Quebec
      • Montreal, Quebec, Canada, H2X 0C1
        • Centre hospitalier de l'Université de Montréal (CHUM)
  • Czechia
      • Brno, Czechia, 656 91
        • Fakultni nemocnice u sv. Anny v Brne
      • Prague, Czechia, 140 21
        • Institut Klinicke a Experimentalni Mediciny
      • Prague, Czechia, 116 36
        • Vseobecna Fakultni Nemocnice V Praze
  • Denmark
      • Copenhagen, Denmark, 2100
        • Rigshospitalet
  • France
      • Créteil, France, 94010
        • Hôpitaux Universitaires Henri Mondor
      • La Roche-sur-Yon, France, 85925
        • Centre Hospitalier Departemental Vendee
      • Marseille, France, 13005
        • Hopital de la Timone
      • Nantes, France, 44093
        • Centre Hospitalier Universitaire de Nantes - Hopital Nord Laennec
      • Pessac, France, 33604
        • Hôpital Haut-Lévêque
      • Toulouse, France, 31059
        • Hôpital Rangueil
  • Germany
      • Cologne, Germany, 50937
        • Uniklinik Koln
      • Heidelberg, Germany, 69120
        • Universitaetsklinikum Heidelberg - Zentrum für Innere Medizin
      • Homburg, Germany, 66421
        • Universitatsklinikum des Saarlandes
      • Münster, Germany, 48149
        • Universitätsklinikum Münster
      • Würzburg, Germany, 97078
        • Universitatsklinikum Wurzburg
  • Greece
      • Athens, Greece, 115 28
        • General Hospital of Athens "Alexandra"
  • Israel
      • Haifa, Israel, 3109601
        • Rambam Health Care Campus
      • Jerusalem, Israel, 9112001
        • Hadassah University Hospital Ein Kerem
      • Rehovot, Israel, 7661041
        • Kaplan Medical Center
  • Italy
      • Ancona, Italy, 60126
        • Azienda Ospedaliero Universitaria delle Marche
      • Florence, Italy, 50134
        • Azienda Ospedaliero - Universitaria Careggi
      • Padova, Italy, 35128
        • Azienda Ospedale Università di Padova
      • Pavia, Italy, 27100
        • Fondazione IRCCS Policlinico San Matteo
      • Pisa, Italy, 56124
        • Fondazione Toscana Gabriele Monasterio per la Ricerca Medica e di Sanita Pubblica
      • Roma, Italy, 00189
        • Azienda Ospedaliera - Universitaria Sant' Andrea
  • Japan
      • Fukuoka, Japan, 810-0001
        • Saiseikai Fukuoka General Hospital
      • Hamamatsu, Japan, 4313192
        • Hamamatsu University Hospital
      • Kumamoto, Japan, 860-8556
        • Kumamoto University Hospital
      • Kurume, Japan, 830-0011
        • Kurume University Hospital
      • Matsumoto, Japan, 390-8621
        • Shinshu University Hospital
      • Okayama, Japan, 700-8558
        • Okayama University Hospital
      • Osaka, Japan, 545-8586
        • Osaka Metropolitan University Hospital
      • Sapporo, Japan, 060-8543
        • Sapporo Medical University Hospital
      • Shinjuku-Ku, Japan, 160-8582
        • Keio University Hospital
    • Fukuoka
      • Kurume-Shi, Fukuoka, Japan, 830-0011
        • Kurume University Hospital
    • Hukuoka [Fukuoka]
      • Fukuoka, Hukuoka [Fukuoka], Japan, 810-0001
        • Saiseikai Fukuoka General Hospital
  • Poland
      • Krakow, Poland, 31- 202
        • Krakowski Szpital Specjalistyczny im. Jana Pawła II
  • Portugal
      • Guimarães, Portugal, 4835-044
        • Hospital da Senhora da Oliveira
      • Guimarães, Portugal, 4835-044
        • Unidade Local de Saude do Alto Ave, E. P. E (Hospital da Senhora da Oliveira Guimaraes)
      • Lisbon, Portugal, 1169-024
        • Unidade Local de Saúde de São José, E. P. E - Hospital de Santa Marta
      • Porto, Portugal, 4099-001
        • Centro Hospitalar Universitário do Porto - Hospital Geral de Santo Antonio
      • Porto, Portugal, 4200-319
        • Centro Hospitalar Universitario de Sao Joao
      • Porto, Portugal, 4099-001
        • Unidade Local de Saude de Santo Antonio, E. P. E - Hospital Geral de Santo Antonio
      • Porto, Portugal, 4200-319
        • Unidade Local de Saúde de São João, EPE
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron
      • Majadahonda, Spain, 28222
        • Hospital Universitario Puerta de Hierro
      • Murcia, Spain, 30120
        • Hospital Clínico Universitario Virgen de la Arrixaca
      • Santiago de Compostela, Spain, 15706
        • Complejo Hospitalario Universitario de Santiago (CHUS)
  • Sweden
      • Gothenburg, Sweden, 413 45
        • Sahlgrenska Universitetssjukhuset
      • Skellefteå, Sweden, 931 86
        • Skellefteå lasarett
  • United Kingdom
      • Hampstead, United Kingdom, NW3 2PF
        • Royal Free London NHS Foundation Trust
      • Liverpool, United Kingdom, L22 0LG
        • Synexus - Merseyside Clinical Research Centre
      • London, United Kingdom, SE1 1YR
        • Richmond Pharmacology
      • Manchester, United Kingdom, M15 6SE
        • Synexus - Merseyside Clinical Research Centre
    • England
      • Bellshill, England, United Kingdom, ML4 3NJ
        • AES - Synexus - Scotland Clinical Research Centre
      • Edgbaston, England, United Kingdom, B15 2SQ
        • AES - Synexus - Midlands
      • Manchester, England, United Kingdom, M15 6SE
        • Synexus - Manchester Clinical Research Centre
    • Wales
      • Cardiff, Wales, United Kingdom, CF15 9SS
        • AES - Synexus - Wales
  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Mayo Clinic
    • California
      • Beverly Hills, California, United States, 90211
        • Cedars-Sinai Medical Center
      • La Jolla, California, United States, 92037
        • Altman Clinical and Translational Research Institute - Center for Clinical Research
      • San Francisco, California, United States, 94143
        • University Of California San Francisco Urology Practice
      • Stanford, California, United States, 94305
        • Stanford University (Leland Stanford Junior University)
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Hospital - Anschutz Medical Campus
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20010
        • Medstar Washington Hospital Center
      • Washington D.C., 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
      • Atlanta, Georgia, United States, 30309
        • Piedmont Heart of Fayetteville
      • Fayetteville, Georgia, United States, 30214
        • Piedmont Atlanta Hospital
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Maywood, Illinois, United States, 60153
        • Loyola University Medical Center
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Health University Hospital
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Medical Center
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Medical Center (KUMC)
    • 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
        • Allina Health Minneapolis Heart Institute - Abbott Northwestern's Heart Hospital
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • Missouri
      • Kansas City, Missouri, United States, 64111
        • Saint Luke's Hospital of Kansas City
      • St 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, 10021
        • Weill Cornell Medicine Cardiology
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • 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
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt Heart and Vascular Institute
    • 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
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin - Madison

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. 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.
  2. Investigator is willing to treat the participant with open-label eplontersen.
  3. Willingness to adhere to vitamin A supplementation per protocol.

Exclusion Criteria:

  1. Permanently discontinued study drug administration while participating in the Index Study (ION 682884-CS2) or IST (ISIS 420915-CS101 Study).
  2. 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.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Eplontersen
Eplontersen 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.
Drug: Eplontersen
Eplontersen will be administered by SC injection.
Other Names:
  • ION-682884
  • IONIS-TTR-LRx

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
Time Frame: Baseline up to 36 months
Baseline up to 36 months
Change From Baseline in Platelet Count
Time Frame: Baseline up to 36 months
Baseline up to 36 months
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
Time Frame: Baseline up to 36 months
Baseline up to 36 months
Change From Baseline in Urine Protein Creatinine Ratio (UPCR)
Time Frame: Baseline up to 36 months
Baseline up to 36 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Change From Baseline in Transthyretin (TTR) Serum Levels
Time Frame: Baseline up to 36 months
Baseline up to 36 months
Change From Baseline in 6-minute Walk Test (6MWT)
Time Frame: Baseline up to 36 months
Baseline up to 36 months
Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ)
Time Frame: Baseline up to 36 months
Baseline up to 36 months

Collaborators and Investigators

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

Sponsor

Ionis Pharmaceuticals, Inc.

Collaborators

AstraZeneca

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)

November 30, 2022

Primary Completion (Estimated)

August 1, 2029

Study Completion (Estimated)

August 1, 2029

Study Registration Dates

First Submitted

July 12, 2022

First Submitted That Met QC Criteria

December 19, 2022

First Posted (Actual)

December 28, 2022

Study Record Updates

Last Update Posted (Actual)

April 17, 2026

Last Update Submitted That Met QC Criteria

April 16, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ION-682884-CS12
  • 2022-000826-74 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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/.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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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