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

Phase 3

Recruiting

• Conditions: Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)
• Interventions: Drug: Eplontersen

• Registration Number: NCT05667493
• Lead Sponsor: Ionis Pharmaceuticals, Inc.

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.

Study Timeline

• Study First Submitted: 2022-07-12
• Study Start: 2022-11-30
• Study First Submitted QC: 2022-12-19
• Study First Posted: 2022-12-28
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-08
• Last Update Posted: 2024-11-12
• Primary Completion: 2029-04
• Study Completion: 2029-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1400

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Eplontersen	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)	Baseline up to 36 months
Change From Baseline in ALT	Baseline up to 36 months
Number of Participants With Clinically Significant Changes From Baseline in Electrocardiogram (ECG) Parameters	Baseline up to 36 months
Change From Baseline in Platelet Count	Baseline up to 36 months
Change From Baseline in Urine Protein Creatinine Ratio (UPCR)	Baseline up to 36 months
Number of Participants With Clinically Significant Changes From Baseline in Thyroid-Stimulating Hormone (TSH)	Baseline up to 36 months
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)	Baseline up to 36 months
Change From Baseline in AST	Baseline up to 36 months
Percentage of Participants With Anti-Drug Antibodies (ADA)	Baseline up to 36 months

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Transthyretin (TTR) Serum Levels	Baseline up to 36 months
Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ)	Baseline up to 36 months
Change From Baseline in 6-minute Walk Test (6MWT)	Baseline up to 36 months
Change From Baseline in Biomarker: N-terminal prohormone of Brain Natriuretic Peptide (NT-proBNP)	Baseline up to 36 months
Change From Baseline in Short Form Health Survey Questionnaire (SF-36)	Baseline up to 36 months
Change From Baseline in 5 Level EuroQol - 5 Dimension (EQ-5D-5L)	Baseline up to 36 months
Change From Baseline in Biomarker: High Sensitivity Cardiac Troponin T (hs-cTnT)	Baseline up to 36 months

Trial Locations

Locations (96)

Azienda Ospedaliera - Universitaria Sant' Andrea; 🇮🇹 Roma, Italy

Unidade Local de Saúde de São José, E. P. E - Hospital de Santa Marta; 🇵🇹 Lisbon, Portugal

Complejo Hospitalario Universitario de Santiago (CHUS); 🇪🇸 Santiago De Compostela, Spain

Kaplan Medical Center; 🇮🇱 Rehovot, Israel

Azienda Ospedaliero - Universitaria Careggi; 🇮🇹 Firenze, Italy

The George Washington Medical Faculty Associates - Foggy Bottom North Pavilion; 🇺🇸 Washington, District of Columbia, United States

Emory Heart and Vascular Center - Emory Clifton Campus; 🇺🇸 Atlanta, Georgia, United States

Loyola University Medical Center; 🇺🇸 Maywood, Illinois, United States

University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

Allina Health Minneapolis Heart Institute - Abbott Northwestern's Heart Hospital; 🇺🇸 Minneapolis, Minnesota, United States

Saint Luke's Hospital of Kansas City; 🇺🇸 Kansas City, Missouri, United States

Carl and Edyth Lindner Research Center at The Christ Hospital; 🇺🇸 Cincinnati, Ohio, United States

Lancaster General Hospital; 🇺🇸 Lancaster, Pennsylvania, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

Stanford University (Leland Stanford Junior University); 🇺🇸 Stanford, California, United States

Houston Methodist Hospital; 🇺🇸 Houston, Texas, United States

University of Wisconsin - Madison; 🇺🇸 Madison, Wisconsin, United States

Instituto Cardiovascular de Buenos Aires; 🇦🇷 Ciudad Autonoma de Buenos Aires, Argentina

Hospital Italiano de Buenos Aires; 🇦🇷 Ciudad Autónoma De Buenos Aires, Argentina

Box Hill Hospital; 🇦🇺 Clayton, Australia

Royal Hobart Hospital; 🇦🇺 Hobart, Australia

Advara HeartCare - Joondalup; 🇦🇺 Joondalup, Australia

Westmead Hospital; 🇦🇺 Westmead, Australia

Princess Alexandra Hospital; 🇦🇺 Woolloongabba, Australia

Medizinische Universität Wien; 🇦🇹 Wien, Austria

Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto; 🇧🇷 Ribeirão Preto, Brazil

Instituto do Coração de São Paulo; 🇧🇷 São Paulo, Brazil

Hôpital Regional de Rimouski; 🇨🇦 Rimouski, Canada

Gordon and Leslie Diamond Health Care Centre; 🇨🇦 Vancouver, Canada

Vseobecna Fakultni Nemocnice v Praze; 🇨🇿 Praha, Czechia

Institut Klinické a Experimentální Medicíny; 🇨🇿 Praha, Czechia

Rigshospitalet; 🇩🇰 Copenhagen, Denmark

Hôpitaux Universitaires Henri Mondor; 🇫🇷 Créteil, France

Hôpital de la Timone; 🇫🇷 Marseille, France

Hôpital Rangueil; 🇫🇷 Toulouse, France

Universitaetsklinikum Heidelberg - Zentrum für Innere Medizin; 🇩🇪 Heidelberg, Germany

Uniklinik Köln; 🇩🇪 Köln, Germany

Fondazione Toscana Gabriele Monasterio per la Ricerca Medica e di Sanita Pubblica; 🇮🇹 Pisa, Italy

Royal Free London NHS Foundation Trust; 🇬🇧 Hampstead, United Kingdom

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Cedars-Sinai Medical Center; 🇺🇸 Beverly Hills, California, United States

Altman Clinical and Translational Research Institute - Center for Clinical Research; 🇺🇸 La Jolla, California, United States

University of Colorado Hospital - Anschutz Medical Campus; 🇺🇸 Aurora, Colorado, United States

MedStar Washington Hospital Center; 🇺🇸 Washington, District of Columbia, United States

Cleveland Clinic Florida; 🇺🇸 Weston, Florida, United States

Piedmont Heart of Fayetteville; 🇺🇸 Atlanta, Georgia, United States

Piedmont Atlanta Hospital; 🇺🇸 Fayetteville, Georgia, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

Indiana University Health University Hospital; 🇺🇸 Indianapolis, Indiana, United States

University of Kansas Medical Center (KUMC); 🇺🇸 Kansas City, Kansas, United States

University of Maryland Medical Center; 🇺🇸 Baltimore, Maryland, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Boston University School of Medicine; 🇺🇸 Boston, Massachusetts, United States

Barnes-Jewish Hospital; 🇺🇸 Saint Louis, Missouri, United States

New York University Langone Cardiology Associates; 🇺🇸 New York, New York, United States

Weill Cornell Medicine Cardiology; 🇺🇸 New York, New York, United States

Columbia University Irving Medical Center; 🇺🇸 New York, New York, United States

University of North Carolina at Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Cleveland Clinic Main Campus; 🇺🇸 Cleveland, Ohio, United States

The Ohio State University College of Medicine; 🇺🇸 Columbus, Ohio, United States

Oregon Health and Science University; 🇺🇸 Portland, Oregon, United States

Penn Presbyterian Medical Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Vanderbilt Heart and Vascular Institute; 🇺🇸 Nashville, Tennessee, United States

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

University of Utah; 🇺🇸 Salt Lake City, Utah, United States

Virginia Commonwealth University; 🇺🇸 Richmond, Virginia, United States

University of Washington; 🇺🇸 Seattle, Washington, United States

Advara HeartCare Murdoch; 🇦🇺 Murdoch, Australia

Advara HeartCare; 🇦🇺 Joondalup, Western Australia, Australia

Liverpool Hospital; 🇦🇺 Liverpool, Australia

Medizinische Universität Graz; 🇦🇹 Graz, Austria

Medizinische Universität Innsbruck; 🇦🇹 Innsbruck, Austria

Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan; 🇧🇪 Brugge, Belgium

University of Calgary; 🇨🇦 Calgary, Alberta, Canada

University Hospital - London Health Sciences Centre; 🇨🇦 London, Ontario, Canada

Centre Hospitalier de l'Université de Montréal (CHUM); 🇨🇦 Montréal, Quebec, Canada

Centre Hospitalier Départemental Vendée; 🇫🇷 La Roche-sur-Yon, France

Centre Hospitalier Universitaire De Nantes - Hôpital Nord Laennec; 🇫🇷 Nantes, France

Hôpital Haut-Lévêque; 🇫🇷 Pessac, France

Universitätsklinikum des Saarlandes; 🇩🇪 Homburg, Germany

Universitätsklinikum Münster; 🇩🇪 Münster, Germany

Universitätsklinikum Würzburg; 🇩🇪 Würzburg, Germany

General Hospital of Athens "Alexandra"; 🇬🇷 Athens, Greece

Rambam Health Care Campus; 🇮🇱 Haifa, Israel

Fondazione IRCCS Policlinico San Matteo; 🇮🇹 Pavia, Italy

Hospital da Senhora da Oliveira; 🇵🇹 Guimarães, Portugal

Centro Hospitalar Universitário do Porto - Hospital Geral de Santo Antonio; 🇵🇹 Porto, Portugal

Centro Hospitalar Universitário de São João; 🇵🇹 Porto, Portugal

Hospital Universitari Vall d'Hebrón; 🇪🇸 Barcelona, Spain

Hospital Universitario Puerta de Hierro; 🇪🇸 Majadahonda, Spain

Hospital Clínico Universitario Virgen de la Arrixaca; 🇪🇸 Murcia, Spain

Sahlgrenska Universitetssjukhuset; 🇸🇪 Göteborg, Sweden

Skellefteå lasarett; 🇸🇪 Skellefteå, Sweden

Richmond Pharmacology; 🇬🇧 London, United Kingdom