Clinical Trial
Study Details
Status
RECRUITING
Study ID #
NCT05667493
Study Start
Primary Completion
Study Completion
Enrollment
1400
Study Type
Interventional
Phase
Phase 3
Interventions
Eplontersen

Eplontersen will be administered by SC injection.

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
Summary

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

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.

Conditions
Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)
Study Contact
Name
Ionis Pharmaceuticals
Role
Contact
Phone
(844) 520-3239
Email
ionisATTRCM2study@clinicaltrialmedia.com
Locations
Facility

Mayo Clinic
Scottsdale, AZ 85259
United States

Facility

Cedars-Sinai Medical Center
Beverly Hills, CA 90211
United States

Facility

Altman Clinical and Translational Research Institute - Center for Clinical Research
La Jolla, CA 92037
United States

Facility

University of Colorado Hospital - Anschutz Medical Campus
Aurora, CO 80045
United States

Facility

MedStar Washington Hospital Center
Washington, DC 20010
United States

Facility

Cleveland Clinic Florida
Weston, FL 33331
United States

Facility

Piedmont Heart of Fayetteville
Atlanta, GA 30309
United States

Facility

Piedmont Atlanta Hospital
Fayetteville, GA 30214
United States

Facility

Northwestern University
Chicago, IL 60611
United States

Facility

Indiana University Health University Hospital
Indianapolis, IN 46202
United States

Facility

University of Kansas Medical Center (KUMC)
Kansas City, KS 66160
United States

Facility

University of Maryland Medical Center
Baltimore, MD 21201
United States

Facility

Massachusetts General Hospital
Boston, MA 02114
United States

Facility

Boston University School of Medicine
Boston, MA 02118
United States

Facility

Mayo Clinic
Rochester, MN 55905
United States

Facility

Barnes-Jewish Hospital
Saint Louis, MO 63110
United States

Facility

New York University Langone Cardiology Associates
New York, NY 10016
United States

Facility

Weill Cornell Medicine Cardiology
New York, NY 10021
United States

Facility

Columbia University Irving Medical Center
New York, NY 10034
United States

Facility

University of North Carolina at Chapel Hill
Chapel Hill, NC 27599
United States

Facility

Duke University Medical Center
Durham, NC 27710
United States

Facility

Cleveland Clinic Main Campus
Cleveland, OH 44195
United States

Facility

The Ohio State University College of Medicine
Columbus, OH 43210
United States

Facility

Oregon Health and Science University
Portland, OR 97239
United States

Facility

Penn Presbyterian Medical Center
Philadelphia, PA 19104
United States

Facility

Vanderbilt Heart and Vascular Institute
Nashville, TN 37232
United States

Facility

University of Texas Southwestern Medical Center
Dallas, TX 75390
United States

Facility

University of Utah
Salt Lake City, UT 84112
United States

Facility

Virginia Commonwealth University
Richmond, VA 23298
United States

Facility

University of Washington
Seattle, WA 98195
United States

Facility

Advara HeartCare Murdoch
Murdoch 6150
Australia

Facility

Advara HeartCare
Joondalup WA 6027
Australia

Facility

Liverpool Hospital
Liverpool 2170
Australia

Facility

Medizinische Universität Graz
8036 Graz
Austria

Facility

Medizinische Universität Innsbruck
6020 Innsbruck
Austria

Facility

Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan
8000 Brugge
Belgium

Facility

University of Calgary
Calgary AB T2N 4Z6
Canada

Facility

University Hospital - London Health Sciences Centre
London ON N6A 5A5
Canada

Facility

Centre Hospitalier de l'Université de Montréal (CHUM)
Montréal QC H2X 0C1
Canada

Facility

Centre Hospitalier Départemental Vendée
85925 La Roche-sur-Yon
France

Facility

Centre Hospitalier Universitaire De Nantes - Hôpital Nord Laennec
44093 Nantes
France

Facility

Hôpital Haut-Lévêque
33604 Pessac
France

Facility

Universitätsklinikum des Saarlandes
66421 Homburg
Germany

Facility

Universitätsklinikum Münster
48149 Münster
Germany

Facility

Universitätsklinikum Würzburg
97078 Würzburg
Germany

Facility

General Hospital of Athens "Alexandra"
115 28 Athens
Greece

Facility

Rambam Health Care Campus
Haifa 3109601
Israel

Facility

Kaplan Medical Center
Rehovot 7661041
Israel

Facility

Azienda Ospedaliero - Universitaria Careggi
50134 Firenze
Italy

Facility

Fondazione IRCCS Policlinico San Matteo
27100 Pavia
Italy

Facility

Hospital da Senhora da Oliveira
4835-044 Guimarães
Portugal

Facility

Centro Hospitalar Universitário do Porto - Hospital Geral de Santo Antonio
4099-001 Porto
Portugal

Facility

Centro Hospitalar Universitário de São João
4200-319 Porto
Portugal

Facility

Hospital Universitari Vall d'Hebrón
08035 Barcelona
Spain

Facility

Hospital Universitario Puerta de Hierro
28222 Majadahonda
Spain

Facility

Hospital Clínico Universitario Virgen de la Arrixaca
30120 Murcia
Spain

Facility

Sahlgrenska Universitetssjukhuset
413 45 Göteborg
Sweden

Facility

Skellefteå lasarett
931 86 Skellefteå
Sweden

Facility

Richmond Pharmacology
London
SE1 1YR
United Kingdom

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.

Eligibility Minimum Age
18 Years
Sexes Eligible for Study
ALL
Eligibility Std Ages
Adult
Older Adult