Clinical trial NCT05667493: An Extension Study to Assess Long-Term Safety of Eplontersen in Adults With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR-CM)
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)
Keywords: Amyloidosis
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: AstraZeneca
First posted: 2022-12-28
Enrollment: 1400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed description: This is a multicenter, open-label, Phase 3 study in up to approximately 1400 participants. Eligible participants will receive eplontersen once every 4 weeks for up to 36 months or 6 months 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. This study will consist of the following periods: less than or equal to (≤) 10-week screening assessment period, up to 36-month treatment period, and up to 6-month post-treatment evaluation period.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
timeFrame: Baseline up to 36 months
measure: Change From Baseline in Platelet Count
timeFrame: Baseline up to 36 months
measure: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
timeFrame: Baseline up to 36 months
measure: Change From Baseline in Urine Protein Creatinine Ratio (UPCR)
timeFrame: Baseline up to 36 months
measure: Change From Baseline in AST
timeFrame: Baseline up to 36 months
measure: Change From Baseline in ALT
timeFrame: Baseline up to 36 months
measure: Number of Participants With Clinically Significant Changes From Baseline in Electrocardiogram (ECG) Parameters
timeFrame: Baseline up to 36 months
measure: Number of Participants With Clinically Significant Changes From Baseline in Thyroid-Stimulating Hormone (TSH)
timeFrame: Baseline up to 36 months
measure: Percentage of Participants With Anti-Drug Antibodies (ADA)
timeFrame: Baseline up to 36 months
Secondary outcomes:
measure: Change From Baseline in Transthyretin (TTR) Serum Levels
timeFrame: Baseline up to 36 months
measure: Change From Baseline in 6-minute Walk Test (6MWT)
timeFrame: Baseline up to 36 months
measure: Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ)
timeFrame: Baseline up to 36 months
measure: Change From Baseline in Short Form Health Survey Questionnaire (SF-36)
timeFrame: Baseline up to 36 months
measure: Change From Baseline in 5 Level EuroQol - 5 Dimension (EQ-5D-5L)
timeFrame: Baseline up to 36 months
measure: Change From Baseline in Biomarker: N-terminal prohormone of Brain Natriuretic Peptide (NT-proBNP)
timeFrame: Baseline up to 36 months
measure: Change From Baseline in Biomarker: High Sensitivity Cardiac Troponin T (hs-cTnT)
timeFrame: Baseline up to 36 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Beverly Hills
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: La Jolla
country: United States
facility: Altman Clinical and Translational Research Institute - Center for Clinical Research
state: California
city: Stanford
country: United States
facility: Stanford University (Leland Stanford Junior University)
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Medical Campus
state: Colorado
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Washington
country: United States
facility: The George Washington Medical Faculty Associates - Foggy Bottom North Pavilion
state: District of Columbia
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Atlanta
country: United States
facility: Piedmont Heart of Fayetteville
state: Georgia
city: Atlanta
country: United States
facility: Emory Heart and Vascular Center - Emory Clifton Campus
state: Georgia
city: Fayetteville
country: United States
facility: Piedmont Atlanta Hospital
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Health University Hospital
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center (KUMC)
state: Kansas
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston University School of Medicine
state: Massachusetts
city: Minneapolis
country: United States
facility: Allina Health Minneapolis Heart Institute - Abbott Northwestern's Heart Hospital
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: New York
country: United States
facility: New York University Langone Cardiology Associates
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine Cardiology
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Carl and Edyth Lindner Research Center at The Christ Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Main Campus
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University College of Medicine
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Lancaster
country: United States
facility: Lancaster General Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Penn Presbyterian Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt Heart and Vascular Institute
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Madison
country: United States
facility: University of Wisconsin - Madison
state: Wisconsin
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Instituto Cardiovascular de Buenos Aires
city: Ciudad Autónoma De Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Murdoch
country: Australia
facility: Advara HeartCare Murdoch
state: West Australia
city: Joondalup
country: Australia
facility: Advara HeartCare
state: Western Australia
city: Clayton
country: Australia
facility: Box Hill Hospital
city: Hobart
country: Australia
facility: Royal Hobart Hospital
city: Joondalup
country: Australia
facility: Advara HeartCare - Joondalup
city: Liverpool
country: Australia
facility: Liverpool Hospital
city: Murdoch
country: Australia
facility: Advara HeartCare Murdoch
city: Westmead
country: Australia
facility: Westmead Hospital
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
city: Graz
country: Austria
facility: Medizinische Universität Graz
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
city: Wien
country: Austria
facility: Medizinische Universität Wien
city: Brugge
country: Belgium
facility: Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan
city: Ribeirão Preto
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto
city: São Paulo
country: Brazil
facility: Instituto do Coração de São Paulo
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: London
country: Canada
facility: University Hospital - London Health Sciences Centre
state: Ontario
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal (CHUM)
state: Quebec
city: Rimouski
country: Canada
facility: Hôpital Regional de Rimouski
city: Vancouver
country: Canada
facility: Gordon and Leslie Diamond Health Care Centre
city: Praha
country: Czechia
facility: Vseobecna Fakultni Nemocnice v Praze
city: Praha
country: Czechia
facility: Institut Klinické a Experimentální Medicíny
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Créteil
country: France
facility: Hôpitaux Universitaires Henri Mondor
city: La Roche-sur-Yon
country: France
facility: Centre Hospitalier Départemental Vendée
city: Marseille
country: France
facility: Hôpital de la Timone
city: Nantes
country: France
facility: Centre Hospitalier Universitaire De Nantes - Hôpital Nord Laennec
city: Pessac
country: France
facility: Hôpital Haut-Lévêque
city: Toulouse
country: France
facility: Hôpital Rangueil
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg - Zentrum für Innere Medizin
city: Homburg
country: Germany
facility: Universitätsklinikum des Saarlandes
city: Köln
country: Germany
facility: Uniklinik Köln
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg
city: Athens
country: Greece
facility: General Hospital of Athens "Alexandra"
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Firenze
country: Italy
facility: Azienda Ospedaliero - Universitaria Careggi
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Pisa
country: Italy
facility: Fondazione Toscana Gabriele Monasterio per la Ricerca Medica e di Sanita Pubblica
city: Roma
country: Italy
facility: Azienda Ospedaliera - Universitaria Sant' Andrea
city: Guimarães
country: Portugal
facility: Hospital da Senhora da Oliveira
city: Lisbon
country: Portugal
facility: Unidade Local de Saúde de São José, E. P. E - Hospital de Santa Marta
city: Porto
country: Portugal
facility: Centro Hospitalar Universitário do Porto - Hospital Geral de Santo Antonio
city: Porto
country: Portugal
facility: Centro Hospitalar Universitário de São João
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebrón
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro
city: Murcia
country: Spain
facility: Hospital Clínico Universitario Virgen de la Arrixaca
city: Santiago De Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago (CHUS)
city: Göteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset
city: Skellefteå
country: Sweden
facility: Skellefteå lasarett
city: Hampstead
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
city: London
country: United Kingdom
facility: Richmond Pharmacology
Study officials:
References: