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)
- Conditions
- Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)
- Interventions
- Drug: Placebo
- Registration Number
- NCT04136171
- Lead Sponsor
- Ionis Pharmaceuticals, Inc.
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 1438
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Eplontersen-matching placebo by subcutaneous injection once every 4 weeks Eplontersen Eplontersen Eplontersen by subcutaneous injection once every 4 weeks
- Primary Outcome Measures
Name Time Method Composite Outcome of Cardiovascular (CV) Mortality and Recurrent CV Clinical Events up to Week 140 Baseline up to Week 140
- Secondary Outcome Measures
Name Time Method Change From Baseline in the 6-minute Walk Test (6MWT) Distance at Week 121 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.
CV Clinical Events up to Week 140 Baseline up to Week 140 All-Cause Mortality up to Week 140 Baseline up to Week 140 Change From Baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Week 121 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.CV Mortality up to Week 140 Baseline up to Week 140
Trial Locations
- Locations (144)
Penn Presbyterian Medical Center
🇺🇸Philadelphia, Pennsylvania, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
University of Pittsburgh Medical School
🇺🇸Pittsburgh, Pennsylvania, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Indiana University Health
🇺🇸Indianapolis, Indiana, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
Alexandra General Hospital
🇬🇷Athens, Greece
Uniklinik Koln
🇩🇪Köln, Germany
Stanford Hospital
🇺🇸Stanford, California, United States
Emory Heart and Vascular Center - Emory Clifton Campus
🇺🇸Atlanta, Georgia, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Boston University School of Medicine
🇺🇸Boston, Massachusetts, United States
The Ohio State University College of Medicine
🇺🇸Columbus, Ohio, United States
Altman Clinical and Translational Research Institute Center for Clinical Research
🇺🇸La Jolla, California, United States
Cleveland Clinic Main Campus
🇺🇸Cleveland, Ohio, United States
Columbia University Irving Medical Center
🇺🇸New York, New York, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
New York University Langone Cardiology Associates
🇺🇸New York, New York, United States
Laurelton Heart Specialists
🇺🇸Rosedale, New York, United States
Charité Universitätsmedizin Berlin
🇩🇪Berlin, Germany
University of Calgary
🇨🇦Calgary, Alberta, Canada
Universitaetsklinikum Heidelberg - Zentrum fur Innere Medizin
🇩🇪Heidelberg, Germany
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Instituto Cardiovascular de Buenos Aires
🇦🇷Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
Instituto Dante Pazzanese de Cardiologia
🇧🇷São Paulo, Brazil
Fondazione IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
The Westmead Institute for Medical Research
🇦🇺Westmead, New South Wales, Australia
Charité Campus Mitte
🇩🇪Berlin, Germany
Centre Hospitalier Universitaire De Nantes - Hôpital Nord Laennec
🇫🇷Saint-Herblain, France
Institut Klinické a Experimentální Medicíny
🇨🇿Prague, Czechia
Hôpital de la Timone
🇫🇷Marseille, France
Azienda Ospedaliera - Universitaria Sant' Andrea
🇮🇹Roma, Italy
Universitätsklinikum Würzburg
🇩🇪Würzburg, Germany
University of Wisconsin - Madison
🇺🇸Madison, Wisconsin, United States
Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona
🇮🇹Ancona, Italy
Fakultní Nemocnice u sv. Anny v Brn
🇨🇿Brno, South Moravian, Czechia
Hôpital Haut-Lévêque
🇫🇷Pessac, France
Box Hill Hospital
🇦🇺Box Hill, Victoria, Australia
Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto
🇧🇷Ribeirão Preto, Brazil
Liverpool Hospital
🇦🇺Liverpool, New South Wales, Australia
Narodowy Instytut Kardiologii Stefana kardyna Wyszyskiego - Pastwowy Instytut Badawczy
🇵🇱Warszawa, Poland
Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant Orsola-Malpighi
🇮🇹Bologna, Italy
Azienda Ospedaliero - Universitaria Careggi
🇮🇹Florence, Italy
Vseobecna Fakultni Nemocnice v Praze
🇨🇿Prague, Czechia
Hôpitaux Universitaires Henri Mondor
🇫🇷Créteil, France
Centre Hospitalier de l'Université de Montréal (CHUM)
🇨🇦Montréal, Quebec, Canada
Centro Avançado de Pesquisa e Estudos para o Diagnóstico CAPED
🇧🇷Ribeirão Preto, Brazil
Synexus - Manchester Clinical Research Centre
🇬🇧Liverpool, United Kingdom
Fondazione Toscana Gabriele Monasterio per la Ricerca Medica e di Sanita Pubblica
🇮🇹Pisa, Italy
Gordon and Leslie Diamond Health Care Centre
🇨🇦Vancouver, British Columbia, Canada
University Hospital - London Health Sciences Centre
🇨🇦London, Ontario, Canada
Hospital Moinhos de Vento
🇧🇷Porto Alegre, Brazil
Centre Hospitalier Départemental Vendée
🇫🇷La Roche-sur-Yon, France
Rambam Health Care Campus
🇮🇱Haifa, Israel
Veterans Affairs Caribbean Healthcare System
🇵🇷San Juan, Puerto Rico
Azienda Ospedale - Università di Padova
🇮🇹Padua, Italy
Synexus - Scotland Clinical Research Centre
🇬🇧Glasgow, Scotland, United Kingdom
Uwajima City Hospital
🇯🇵Uwajima-shi, Ehime, Japan
Saiseikai Fukuoka General Hospital
🇯🇵Fukuoka, Hukuoka, Japan
Hospital Universitario Puerta de Hierro - Majadahonda
🇪🇸Majadahonda, Spain
Centro Hospitalar Universitário do Porto - Hospital Geral de Santo Antonio
🇵🇹Porto, Portugal
Hospital Universitari Vall d'Hebrón
🇪🇸Barcelona, Spain
Sapporo Medical University Hospital
🇯🇵Sapporo-shi, Hokkaido, Japan
Osaka Metropolitan University Hospital
🇯🇵Osaka-shi, Osaka, Japan
Universitätsklinikum des Saarlandes
🇩🇪Homburg, Saarland, Germany
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Medizinische Universität Wien
🇦🇹Vienna, Austria
Ziekenhuis Oost-Limburg - Campus Sint-Jan
🇧🇪Genk, Limburg, Belgium
Lancaster General Hospital
🇺🇸Lancaster, Pennsylvania, United States
Medizinische Universität Graz
🇦🇹Graz, Styria, Austria
Hôpital Rangueil
🇫🇷Toulouse, Occitanie, France
Rigshospitalet
🇩🇰Copenhagen, Hovedstaden, Denmark
Odense Universitetshospital
🇩🇰Odense, Syddanmark, Denmark
Okayama University Hospital
🇯🇵Okayama-shi,, Okayama, Japan
University of California, San Francisco (UCSF) - Medical Center
🇺🇸San Francisco, California, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Minneapolis Heart Institute
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic - Rochester
🇺🇸Rochester, Minnesota, United States
Carl and Edyth Lindner Research Center at The Christ Hospital
🇺🇸Cincinnati, Ohio, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Froedtert & Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Advara HeartCare Murdoch
🇦🇺Murdoch, West Australia, Australia
A Beneficência Portuguesa de São Paulo - Unidade Mirante
🇧🇷São Paulo, Brazil
Cleveland Clinic Florida
🇺🇸Weston, Florida, United States
Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
Barnes-Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
GenesisCare Joondalup
🇦🇺Joondalup, Western Australia, Australia
Instituto do Coração de São Paulo
🇧🇷São Paulo, Brazil
University of Washington
🇺🇸Seattle, Washington, United States
Mayo Clinic - Arizona
🇺🇸Phoenix, Arizona, United States
The George Washington Medical Faculty Associates - Foggy Bottom North Pavilion
🇺🇸Washington, District of Columbia, United States
Piedmont Heart of Fayetteville
🇺🇸Fayetteville, Georgia, United States
MedStar Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
The University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Weill Cornell Medicine Cardiology
🇺🇸New York, New York, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
GenesisCare Murdoch
🇦🇺Murdoch, West Australia, Australia
Hospital Italiano de Buenos Aires
🇦🇷Ciudad Autónoma De Buenos Aires, Buenos Aires, Argentina
Royal Hobart Hospital
🇦🇺Hobart, Tasmania, Australia
Advara HeartCare
🇦🇺Joondalup, Western Australia, Australia
Advara Heartcare
🇦🇺Leabrook, South Australia, Australia
Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan
🇧🇪Brugge, West-Vlaanderen, Belgium
Universidade Estadual de Campinas
🇧🇷Campinas, Brazil
Hôpital Regional de Rimouski
🇨🇦Rimouski, Quebec, Canada
Universitätsklinikum Münster
🇩🇪Münster, Germany
Hadassah University Hospital Ein Kerem
🇮🇱Jerusalem, Israel
Kaplan Medical Center
🇮🇱Rehovot, Israel
Kurume University Hospital
🇯🇵Kurume-shi, Fukuoka, Japan
Hospital of the University of Occupational and Environmental Health
🇯🇵Kitakyushu-shi, Fukuoka, Japan
University Hospital Kyoto Prefectural University of Medicine
🇯🇵Kyoto-shi, Kyoto, Japan
Hamamatsu University Hospital
🇯🇵Hamamatsu, Shizuoka, Japan
Kokura Memorial Hospital
🇯🇵Kitakyushu, Hukuoka, Japan
Keio University Hospital
🇯🇵Shinjuku-Ku, Tokyo, Japan
Krakowski Szpital Specjalistyczny im. Jana Pawa II
🇵🇱Kraków, Poland
Shinshu University Hospital
🇯🇵Matsumoto, Nagano, Japan
Kumamoto University Hospital
🇯🇵Kumamoto, Japan
Hospital da Senhora da Oliveira - Guimarães
🇵🇹Guimarães, Portugal
Centro Hospitalar Universitário de Lisboa Central - Hospital de Santa Marta
🇵🇹Lisbon, Portugal
Centro Hospitalar Universitário de São João
🇵🇹Porto, Portugal
Hospital Clínico Universitario Virgen de la Arrixaca
🇪🇸Murcia, Spain
Skellefteå lasarett
🇸🇪Skellefteå, Sweden
Sahlgrenska Universitetssjukhuset
🇸🇪Göteborg, Sweden
Complejo Hospitalario Universitario de Santiago
🇪🇸Santiago de Compostela, Spain
Synexus - Wales
🇬🇧Cardiff, Wales, United Kingdom
Synexus Midlands Clinical Research Centre
🇬🇧Edgbaston, United Kingdom
Synexus - North Tees Clinical Research Centre
🇬🇧Hexham, United Kingdom
Synexus - Merseyside Clinical Research Centre
🇬🇧Liverpool, United Kingdom
Richmond Pharmacology
🇬🇧London, United Kingdom
University of Colorado Hospital - Anschutz Medical Campus
🇺🇸Aurora, Colorado, United States
Saint Luke's Hospital of Kansas City
🇺🇸Kansas City, Missouri, United States
Louisiana State University Health Sciences Center
🇺🇸New Orleans, Louisiana, United States
Tulane University Heart and Vascular Institute
🇺🇸New Orleans, Louisiana, United States
Ochsner Health System
🇺🇸New Orleans, Louisiana, United States
The University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Virginia Commonwealth University (VCU)
🇺🇸Richmond, Virginia, United States
Royal Free London NHS Foundation Trust
🇬🇧London, United Kingdom
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
Medizinische Universität Innsbruck
🇦🇹Innsbruck, Tyrol, Austria