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.
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
- Conditions the study is for
- Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)
- 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
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
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
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
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
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
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
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
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
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
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
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
Austria3 sites
Medizinische Universität Graz
Graz, 8036
Medizinische Universität Innsbruck
Innsbruck, 6020
Medizinische Universität Wien
Vienna, 1090
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
Israel3 sites
Rambam Health Care Campus
Haifa, 3109601
Hadassah University Hospital Ein Kerem
Jerusalem, 9112001
Kaplan Medical Center
Rehovot, 7661041
Argentina2 sites
Hospital Italiano de Buenos Aires
Buenos Aires, C1199ABB
Instituto Cardiovascular de Buenos Aires
Buenos Aires, C1428ART
Belgium2 sites
Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan
Bruges, 8000
Ziekenhuis Oost-Limburg - Campus Sint-Jan
Limbourg, 3600
Sweden2 sites
Sahlgrenska Universitetssjukhuset
Gothenburg, 413 45
Skellefteå lasarett
Skellefteå, 931 86
Poland1 site
Krakowski Szpital Specjalistyczny im. Jana Pawła II
Krakow, 31- 202
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 group | Role | What they receive |
|---|---|---|
| Eplontersen | Experimental | 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. Receives: Drug: Eplontersen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
Measured: Baseline up to 36 months
Change From Baseline in Platelet Count
Measured: Baseline up to 36 months
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
Measured: Baseline up to 36 months
Change From Baseline in Urine Protein Creatinine Ratio (UPCR)
Measured: Baseline up to 36 months
Secondary outcomes (3)
Change From Baseline in Transthyretin (TTR) Serum Levels
Measured: Baseline up to 36 months
Change From Baseline in 6-minute Walk Test (6MWT)
Measured: Baseline up to 36 months
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.
- First posted28 Dec 2022
- Study start30 Nov 2022
- Primary completionAug 2029 (estimated)
- Study completionAug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)Studies of the same condition, open and under way.
- More trials run by Ionis Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
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/.