Acoramidis Transthyretin Amyloidosis Prevention Trial in the Young (ACT-EARLY) Study in Asymptomatic Carriers of a Pathogenic TTR Variant

Summary

Transthyretin amyloidosis (ATTR) is a disease where the normally occurring transthyretin (TTR) protein falls apart and forms amyloid, a sticky plaque-like substance that accumulates in different organs in the body and can cause damage to the organ. There are two ways that the TTR protein can fall apart. One way occurs as a person ages, where the normal TTR protein can fall apart and form amyloid that may no longer be sufficiently cleared by the body. This type of ATTR is known as wild-type ATTR (ATTRwt). The other way occurs when a person inherits a defective TTR gene that causes the TTR protein to spontaneously fall apart. This form of the disease is known as variant ATTR (ATTRv) and can be detected in adults by a genetic test of their TTR gene before they age. Amyloid build-up in the heart causes the heart wall to become thick and stiff and can result in heart failure and even death. Accumulation of TTR amyloid in the heart is known as transthyretin amyloid cardiomyopathy or ATTR-CM. Amyloid can also deposit in the nerve tissues leading to nerve problems. Accumulation of TTR in the nerves is known as transthyretin amyloid polyneuropathy or ATTR-PN. Acoramidis is an experimental drug designed to bind tightly to TTR in the blood and stabilize its structure, so it does not form the harmful amyloid plaques that can cause damage to organs. This study is intended to determine if treatment with acoramidis in participants with ATTRv who have not yet developed any symptoms of disease can prevent or delay the development of ATTR-CM or ATTR-PN disease. If adults with an inherited defective TTR gene are treated early before any of the symptoms of disease have developed, it may be possible to delay the onset or prevent the disease entirely.

Interventions

• Acoramidis · DRUG

  TTR stabilizer administered orally twice daily (BID)

• Placebo oral tablet · DRUG

  Non-active control administered orally twice daily (BID)

Published eligibility criteria

Verbatim from the registry. Only the site can decide how these apply to a specific patient.

Key Inclusion Criteria:

* Male or female ≥ 18 to ≤ 75 years of age inclusive.
* Participants must have an established genotype (hetero- or homozygosity) through a medically-indicated genetic test of a TTR gene variant that is known to be pathogenic or likely pathogenic (eg, V30M/p.V50M, V122I/p.V142I, T60A/p.T80A, or all other pathogenic TTR variants).
* Participant's age is within 10 years younger than or older than PADO.

Key Exclusion Criteria:

* Evidence of ATTR-CM or ATTR-PN.
* Current or past (within last 1 to 12 months, depending on specific agent) treatment with other TTR modifying therapies.
* Contraindication to or inability to undergo cardiac magnetic resonance testing.
* Major organ dysfunction, including: kidney disease, liver disease, heart disease (including cardiomyopathy), neuropathy
* Other diseases or conditions such has cancer within 5 years, untreated hyperthyroidism or hypothyroidism, type 1 diabetes, active hepatitis B or C, HIV.
* Major surgery within the past 3 months or planned during the next 12 months.
* Known hypersensitivity to acoramidis.

Sites (104)

• University of California, San Diego (UCSD) - Medical Center, La Jolla, California · RECRUITING
• University of California, Los Angeles (UCLA) - David Geffen School of Medicine, Los Angeles, California · RECRUITING
• University of California, San Francisco (UCSF), San Francisco, California · RECRUITING
• Stanford University, Stanford, California · RECRUITING
• University of Colorado Anschutz, Aurora, Colorado · RECRUITING
• Yale University School of Medicine - Section of Cardiology, New Haven, Connecticut · RECRUITING
• MedStar Washington Hospital Center - MedStar Heart and Vascular Institute, Washington D.C., District of Columbia · RECRUITING
• Mayo Clinic - Jacksonville, Jacksonville, Florida · RECRUITING
• University of Miami, Miami, Florida · RECRUITING
• Cleveland Clinic Florida, Weston, Florida · RECRUITING
• Emory University School of Medicine, Atlanta, Georgia · RECRUITING
• John H. Stroger, Jr. Hospital of Cook County, Chicago, Illinois · RECRUITING
• University of Chicago - Medical Center, Chicago, Illinois · RECRUITING
• University of Maryland Medical Center, Baltimore, Maryland · RECRUITING
• Johns Hopkins University, Baltimore, Maryland · RECRUITING
• Massachusetts General Hospital, Boston, Massachusetts · RECRUITING
• Brigham and Women's Hospital, Boston, Massachusetts · RECRUITING
• Boston University (BU) School of Medicine, Boston, Massachusetts · RECRUITING
• Henry Ford Health System, Detroit, Michigan · RECRUITING
• Mayo Clinic - Rochester, Rochester, Minnesota · RECRUITING
• St. Luke's Hospital of Kansas City, Kansas City, Missouri · RECRUITING
• Washington University in St. Louis, St Louis, Missouri · RECRUITING
• Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey · RECRUITING
• New York University (NYU) School of Medicine - Langone Medical Center, New York, New York · RECRUITING
• Mount Sinai Hospital, New York, New York · RECRUITING
• Columbia University Medical Center, New York, New York · RECRUITING
• Laurelton Heart Specialists, Rosedale, New York · RECRUITING
• Duke University Medical Center, Durham, North Carolina · RECRUITING
• Cleveland Clinic, Cleveland, Ohio · RECRUITING
• Oregon Health & Science University, Portland, Oregon · RECRUITING
• Penn Presbyterian Medical Center, Philadelphia, Pennsylvania · RECRUITING
• University of Pittsburgh Medical Center, Presbyterian Hospital, Pittsburgh, Pennsylvania · RECRUITING
• Medical University of South Carolina (MUSC), Charleston, South Carolina · RECRUITING
• Prisma Health Cancer Institute, Greenville, South Carolina · RECRUITING
• National Neuromuscular Research Institute, Austin, Texas · RECRUITING
• University of Texas Southwestern, Dallas, Texas · RECRUITING
• University of Utah, Salt Lake City, Utah · RECRUITING
• INOVA Fairfax Hospital, Falls Church, Virginia · RECRUITING
• Virginia Commonwealth University, Richmond, Virginia · RECRUITING
• University of Washington Medical Center, Seattle, Washington · RECRUITING
• Hospital Italiano de Buenos Aires, Buenos Aires, Argentina · RECRUITING
• Hospital Britanico de Buenos Aires, Buenos Aires, Argentina · RECRUITING
• ICBA - Instituto Cardiovascular de Buenos Aires S.A., CABA, Argentina · RECRUITING
• St Vincent's Hospital Sydney, Darlinghurst, Australia · RECRUITING
• Fiona Stanley Hospital, Murdoch, Australia · RECRUITING
• Westmead Hospital, Westmead, Australia · RECRUITING
• Princess Alexandra Hospital, Woolloongabba, Australia · RECRUITING
• UZ Leuven, Leuven, Belgium · RECRUITING
• Fundacao Centro Medico de Campinas, Campinas, Brazil · RECRUITING
• Instituto do Coracao (InCor) do Hospital das Clinicas da FMUSP, Cerqueira César, Brazil · RECRUITING
• CAPED - Centro Avancado de Pesquisa, Estudos e Diagnostico, Ribeirão Preto, Brazil · RECRUITING
• Cardiopulmonar da Bahia S.A. (Hospital Cardio Pulmonar), Salvador, Brazil · RECRUITING
• University of Calgary, Calgary, Alberta, Canada · RECRUITING
• University of British Columbia, Vancouver, British Columbia, Canada · RECRUITING
• St. Michael's Hospital, Toronto, Ontario, Canada · RECRUITING
• Aarhus University Hospital, Aarhus, Denmark · RECRUITING
• CHU Bordeaux - Hopital Pellegrin, Bordeaux, France · RECRUITING
• AP-HP Hopital Henri Mondor, Créteil, France · RECRUITING
• AP-HP Hopital Bicetre, Le Kremlin-Bicêtre, France · RECRUITING
• CHU Rennes, Rennes, France · RECRUITING
• CHU de Toulouse - Hopital Rangueil, Toulouse, France · RECRUITING
• Charite Universitaetsmedizin Berlin, Berlin, Germany · RECRUITING
• Universitaetsklinikum Heidelberg, Heidelberg, Germany · RECRUITING
• Universitaetsmedizin der Johannes Gutenberg - Universitaet Mainz, Mainz, Germany · RECRUITING
• Hippokration General Hospital of Athens, Athens, Greece · RECRUITING
• General Hospital of Athens - Alexandra, Athens, Greece · RECRUITING
• The Mater Misericordiae University Hospital, Dublin, Ireland · RECRUITING
• Tallaght University Hospital - The Adelaide and Meath Hospital, Dublin, Ireland · RECRUITING
• Azienda Ospedaliero-Universitaria di Bologna IRCCS Policlinico di S.Orsola, Bologna, Italy · RECRUITING
• Azienda Ospedaliero-Universitaria Careggi, Florence, Italy · RECRUITING
• Fondazione IRCCS Policlinico San Matteo, Pavia, Italy · RECRUITING
• Fondazione Toscana Gabriele Monasterio per la Ricerca Medica e di Sanità Pubblica - Ospedale San Cataldo, Pisa, Italy · RECRUITING
• Azienda Ospedaliero Universitaria Policlinico Umberto I, Roma, Italy · RECRUITING
• Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore, Rome, Italy · RECRUITING
• Azienda Ospedaliero-Universitaria Sant'Andrea, Rome, Italy · RECRUITING
• Kumamoto University Hospital, Kumamoto, Japan · RECRUITING
• Shinshu University Hospital, Nagano, Japan · RECRUITING
• University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia · RECRUITING
• CHU de Fort de France, Fort-de-France, Martinique · RECRUITING
• National Institute of Medical Sciences and Nutrition - Salvador Zubiran(INCMNSZ), Tlalpan, Mexico · RECRUITING
• University Medical Center Groningen, Groningen, Netherlands · RECRUITING
• Maastricht University Medical Center, Maastricht, Netherlands · RECRUITING
• Erasmus MC, Rotterdam, Netherlands · RECRUITING
• Universitair Medisch Centrum Utrecht, Utrecht, Netherlands · RECRUITING
• Unidade Local de Saude de Santa Maria EPE - Hospital de Santa Maria, Lisbon, Portugal · RECRUITING
• Unidade Local de Saude de Santo Antonio EPE - Hospital de Santo Antonio, Porto, Portugal · RECRUITING
• National University Hospital - National University Health System, Singapore, Singapore · RECRUITING
• Singapore General Hospital, Singapore, Singapore · RECRUITING
• Seoul National University Hospital, Seoul, South Korea · RECRUITING
• Severance Hospital, Yonsei University Health System, Seoul, South Korea · RECRUITING
• Samsung Medical Center, Seoul, South Korea · RECRUITING
• Seoul St. Mary's Hospital, Seoul, South Korea · RECRUITING
• Hospital Universitario de A Coruna, A Coruña, Spain · RECRUITING
• Hospital Universitari de Bellvitge, Barcelona, Spain · RECRUITING
• Hospital Universitario Juan Ramon Jimenez, Huelva, Spain · RECRUITING
• Hospital Universitario Puerta de Hierro, Majadahonda, Spain · RECRUITING
• Hospital Universitario Son Llatzer, Palma de Mallorca, Spain · RECRUITING
• Hospital Clinico Universitario de Salamanca, Salamanca, Spain · RECRUITING
• Norrlands universitetssjukhus (University Hospital of Umea), Umeå, Sweden · RECRUITING
• Changhua Christian Hospital - Taiwan, Changhua, Taiwan · RECRUITING
• National Taiwan University Hospital, Taipei, Taiwan · RECRUITING
• Taipei Veterans General Hospital, Taipei, Taiwan · RECRUITING
• St. Bartholomew's Hospital, London, United Kingdom · RECRUITING
• University College London Hospitals NHS Foundation Trust, London, United Kingdom · RECRUITING