An Extension Study to Assess Long-Term Safety of Eplonter... | NCT05667493

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

NCT05667493

Sponsor

Ionis Pharmaceuticals, Inc.

Status

Enrolling by invitation

Last Update Posted

Apr 17, 2026Actual

Enrollment

1,400Estimated

Phase

Phase 3

Conditions

Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)

Interventions

Eplontersen

Countries

United States
Argentina
Australia
Austria
Belgium
Brazil
Canada
Czechia
Denmark
France
Germany
Greece
Israel
Italy
Japan
Poland
Portugal
Spain
Sweden
United Kingdom

Protocol Section

Identification Module Status Module Sponsor/Collaborators Module Oversight Module Description Module Conditions Module Design Module Arms/Interventions Module Outcomes Module Eligibility Module Contacts/Locations Module References Module IPD Sharing Statement Module

Results Section

Participant Flow Module Baseline Characteristics Module Outcome Measures Module Adverse Events Module More Info Module

Annotation Section

Annotation Module

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module Condition Browse Module Intervention Browse Module

Protocol Section

Identification Module

NCT ID

ID	Type	Description	Link
2022-000826-74	EudraCT Number

Status Module

Record Verification Date

Apr 2026

Overall Recruitment Status or Expanded Access Status

Enrolling by invitation

Last Known Status

Not provided

Delayed Posting

Not provided

Why Stopped

Not provided

Expanded Access Info

Start Date

Nov 30, 2022Actual

Primary Completion Date

Aug 2029Estimated

Completion Date

Aug 2029Estimated

First Submitted Date

Jul 12, 2022

First Submission Date that Met QC Criteria

Dec 19, 2022

First Posted Date

Dec 28, 2022Actual

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

Apr 16, 2026

Last Update Posted Date

Apr 17, 2026Actual

Name	Class
AstraZeneca	INDUSTRY

Oversight Module

Has Data Monitoring Committee (DMC)

Is FDA Regulated Drug

Yes

Is FDA Regulated Device

Is Unapproved Device

Not provided

Pediatric Postmarket Surveillance of a Device Product

Not provided

Product Exported from US

Not provided

FDAAA801 Violation

Not provided

Description Module

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 extension, Phase 3 study in up to approximately 1400 participants from the 682884-CS2 study. Eligible participants will receive eplontersen once every 4 weeks for up to 36 months or until 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.

Design Module

Study Type

Interventional

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Not provided

Target Follow-Up Duration

Not provided

Phases

Phase 3

Interventional Study Design

Allocation

Biospecimen

No data available

No data is available for this block.

Enrollment

1,400Estimated

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Eplontersen	Experimental	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.	Drug: Eplontersen

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Eplontersen	Drug	Eplontersen will be administered by SC injection.	Eplontersen

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)		Baseline up to 36 months
Change From Baseline in Platelet Count		Baseline up to 36 months
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)		Baseline up to 36 months
Change From Baseline in Urine Protein Creatinine Ratio (UPCR)		Baseline up to 36 months

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Transthyretin (TTR) Serum Levels		Baseline up to 36 months
Change From Baseline in 6-minute Walk Test (6MWT)		Baseline up to 36 months

Other Outcomes

Not provided

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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.
Investigator is willing to treat the participant with open-label eplontersen.
Willingness to adhere to vitamin A supplementation per protocol.

Exclusion Criteria:

Permanently discontinued study drug administration while participating in the Index Study (ION 682884-CS2) or IST (ISIS 420915-CS101 Study).
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.

Accepts Healthy Volunteers

Sex

All

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

18 Years

Maximum Age

Not provided

Standard Ages

AdultOlder Adult

Study Population

Not provided

Sampling Method

Not provided

Contacts/Locations Module

Central Contacts

Not provided

Overall Officials

Not provided

Locations

Facility	Status	City	State	ZIP	Country	Contacts
Mayo Clinic		Scottsdale	Arizona	85259	United States
Cedars-Sinai Medical Center

IPD Sharing Statement Module

Plan to Share IPD

Yes

Description

Ionis may share anonymized individual participant data, aggregated clinical data, and other types of data that support the results in this study. Data requests from qualified researchers will be considered once all three of the following criteria are met: (1) 12 months from marketing approval of the study drug in both the United States and European Union; (2) 18 months from conclusion of the study; and (3) 6 months from publication of study article. Access would be via a secure environment and is contingent upon approval of a research proposal and entry into an appropriate data use agreement. Requests to access data can be submitted via the website https://vivli.org/ourmember/ionis/.

Types

Not provided

Time Frame

Not provided

Access Criteria

Not provided

URL

Not provided

ID	Term
D057165	Proteostasis Deficiencies
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases