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

Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM) Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05667493
• Other study ID #: ION-682884-CS12
• Secondary ID: 2022-000826-74
• Status: Recruiting
• Phase: Phase 3
• Start date: November 30, 2022
• Est. completion date: August 2029

Study information

• Verified date: March 2024
• Source: Ionis Pharmaceuticals, Inc.
• Contact: Ionis Pharmaceuticals
• Phone: (844) 520-3239
• Email: ionisATTRCM2study[@]clinicaltrialmedia.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1400
• Est. completion date: August 2029
• Est. primary completion date: April 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Amyloidosis
• Cardiomyopathies
• Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)

Intervention

Drug:
• Eplontersen
Eplontersen will be administered by SC injection.

Locations

Country	Name	City	State
Australia	Advara HeartCare	Joondalup	Western Australia
Australia	Liverpool Hospital	Liverpool
Australia	Advara HeartCare Murdoch	Murdoch	West Australia
Austria	Medizinische Universität Graz	Graz
Austria	Medizinische Universität Innsbruck	Innsbruck
Belgium	Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan	Brugge
Canada	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
France	Centre Hospitalier Départemental Vendée	La Roche-sur-Yon
France	Centre Hospitalier Universitaire De Nantes - Hôpital Nord Laennec	Nantes
France	Hôpital Haut-Lévêque	Pessac
Germany	Universitätsklinikum des Saarlandes	Homburg
Germany	Universitätsklinikum Münster	Münster
Germany	Universitätsklinikum Würzburg	Würzburg
Greece	General Hospital of Athens "Alexandra"	Athens
Israel	Rambam Health Care Campus	Haifa
Israel	Kaplan Medical Center	Rehovot
Italy	Azienda Ospedaliero - Universitaria Careggi	Firenze
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia
Portugal	Hospital da Senhora da Oliveira	Guimarães
Portugal	Centro Hospitalar Universitário de São João	Porto
Portugal	Centro Hospitalar Universitário do Porto - Hospital Geral de Santo Antonio	Porto
Spain	Hospital Universitari Vall d'Hebrón	Barcelona
Spain	Hospital Universitario Puerta de Hierro	Majadahonda
Spain	Hospital Clínico Universitario Virgen de la Arrixaca	Murcia
Sweden	Sahlgrenska Universitetssjukhuset	Göteborg
Sweden	Skellefteå lasarett	Skellefteå
United Kingdom	Richmond Pharmacology	London
United States	Piedmont Heart of Fayetteville	Atlanta	Georgia
United States	University of Colorado Hospital - Anschutz Medical Campus	Aurora	Colorado
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Cedars-Sinai Medical Center	Beverly Hills	California
United States	Boston University School of Medicine	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	Cleveland Clinic Main Campus	Cleveland	Ohio
United States	The Ohio State University College of Medicine	Columbus	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	Piedmont Atlanta Hospital	Fayetteville	Georgia
United States	Indiana University Health University Hospital	Indianapolis	Indiana
United States	University of Kansas Medical Center (KUMC)	Kansas City	Kansas
United States	Altman Clinical and Translational Research Institute - Center for Clinical Research	La Jolla	California
United States	Vanderbilt Heart and Vascular Institute	Nashville	Tennessee
United States	Columbia University Irving Medical Center	New York	New York
United States	New York University Langone Cardiology Associates	New York	New York
United States	Weill Cornell Medicine Cardiology	New York	New York
United States	Penn Presbyterian Medical Center	Philadelphia	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	Barnes-Jewish Hospital	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	Mayo Clinic	Scottsdale	Arizona
United States	University of Washington	Seattle	Washington
United States	MedStar Washington Hospital Center	Washington	District of Columbia
United States	Cleveland Clinic Florida	Weston	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Ionis Pharmaceuticals, Inc.	AstraZeneca

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  France,  Germany,  Greece,  Israel,  Italy,  Portugal,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)		Baseline up to 36 months
Primary	Change From Baseline in Platelet Count		Baseline up to 36 months
Primary	Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)		Baseline up to 36 months
Primary	Change From Baseline in Urine Protein Creatinine Ratio (UPCR)		Baseline up to 36 months
Primary	Change From Baseline in AST		Baseline up to 36 months
Primary	Change From Baseline in ALT		Baseline up to 36 months
Primary	Number of Participants With Clinically Significant Changes From Baseline in Electrocardiogram (ECG) Parameters		Baseline up to 36 months
Primary	Number of Participants With Clinically Significant Changes From Baseline in Thyroid-Stimulating Hormone (TSH)		Baseline up to 36 months
Primary	Percentage of Participants With Anti-Drug Antibodies (ADA)		Baseline up to 36 months
Secondary	Change From Baseline in Transthyretin (TTR) Serum Levels		Baseline up to 36 months
Secondary	Change From Baseline in 6-minute Walk Test (6MWT)		Baseline up to 36 months
Secondary	Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ)		Baseline up to 36 months
Secondary	Change From Baseline in Short Form Health Survey Questionnaire (SF-36)		Baseline up to 36 months
Secondary	Change From Baseline in 5 Level EuroQol - 5 Dimension (EQ-5D-5L)		Baseline up to 36 months
Secondary	Change From Baseline in Biomarker: N-terminal prohormone of Brain Natriuretic Peptide (NT-proBNP)		Baseline up to 36 months
Secondary	Change From Baseline in Biomarker: High Sensitivity Cardiac Troponin T (hs-cTnT)		Baseline up to 36 months