Long-term Safety of Eplontersen Treated aTTR Patients and in Liver Transplant and Severely Hepatic Impaired Subpopulations (sTTRing)

Post-Authorisation Safety Study: A Cohort Event Monitoring Study to Characterise the Use of Eplontersen in Patients With Prior Liver Transplant and Pre-existing Severe Hepatic Impairment and to Assess Long-term Safety Among All New Users of Eplontersen (sTTRing)

The aim of this observational cohort study is to characterise use of eplontersen in patients with prior liver transplant or with pre-existing severe hepatic impairment, as well as to assess long-term safety among all new users of eplontersen; all are areas of missing information

Primary objectives are:

1. To describe demographic and clinical characteristics of patients at eplontersen initiation, including the prevalence of prior liver transplant (overall and by reason for liver transplant), and the prevalence of severe hepatic impairment; and to describe patients in these subgroups (prior liver transplant, severe hepatic impairment).
2. To describe long-term safety in patients who initiate eplontersen treatment, including onset of new clinical events, abnormal laboratory values and serious adverse events.

Study Overview

• Status: Not yet recruiting
• Conditions: Transthyretin Amyloidosis; Transthyretin Amyloidosis With Cardiomyopathy; Transthyretin Amyloidosis With Polyneuropathy
• Intervention / Treatment: Other: None ( observational study )

Detailed Description

Study D8450R00003 enrolls adults (≥18 years) with a confirmed ATTR diagnosis at the time of informed consent. The sTTRing study will represent a subset of D8450R00003 participants who consent to secondary research use of their data and who initiated eplontersen treatment within 1 year prior to enrollment in D8450R00003. For comparative analyses, patients not exposed to eplontersen who initiated alternative ATTR therapies during the D8450R00003 observation period will also be included.

sTTRing data collection will begin in Q3 2026 and conclude in Q1 2032. Interim analyses will be reported annually from Q3 2027 through Q3 2031, with a final report submitted in Q1 2033.

The primary endpoints supporting the primary study objective are: (1) the prevalence of patients with a history of liver transplantation, categorized by reason for liver transplant, and (2) the prevalence of severe hepatic impairment. Safety outcomes will be summarized by incidence risk and event rates across prespecified time intervals (e.g., 0-6 months and from 7 months to the end of available follow-up) and over the full duration of follow-up. These summaries will be included in interim reports as part of both primary and secondary objectives.

Cohort Event Monitoring will be used to identify safety events requiring further characterization. When more than 10 events are observed for a given outcome, cumulative hazard rates will be estimated. To optimize sample size, comparative analyses will be conducted, where feasible, at the final analysis and presented in the final report.

• Study Type: Observational
• Enrollment (Estimated): 320

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The D8450R00003 study cohort includes individuals with confirmed diagnosis of ATTR, aged ≥18 years at the time of providing the informed consent. The sTTRing study population will be a subset of the D8450R00003 cohort who meet the additional criteria below.

Description

Inclusion Criteria:

1. D8450R00003 participants who consented to have their data used for future related research studies.
2. D8450R00003 participants who initiated eplontersen treatment up to 1-year prior to enrolment into D8450R00003 study observation period, irrespective of ATTR phenotype or genotype. For the comparative analyses, patients unexposed to eplontersen treatment and who initiated another ATTR treatment during D8450R00003 study observation period will be included

Exclusion Criteria:

1. Patients with exposure to eplontersen more than 1-year prior to enrolment into D8450R00003 study.
2. Patients who participated in an interventional ATTR study in the 12-months prior to enrolment into D8450R00003 study.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Eplontersen users; D8450R00003 population of new and prior eplontersen users (including prior liver transplant and severe hepatic impairment subpopulations)	Other: None ( observational study ); Not applicable this is observational study no intervention is planned.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Demographic and clinical characteristics of eplontersen users, including the prevalence of prior liver transplant and severe hepatic impairment	Prevalence of liver transplant prior to eplontersen initiation (overall by reason for liver transplant),; Prevalence of severe hepatic impairment prior to eplontersen initiation These will be summarised as prevalence proportion and 95% CI. Secondary outcomes: Demographic characteristics (e.g. age, sex), general health factors (e.g. BMI), indication related characteristics (e.g. ATTR diagnoses dates and duration since first diagnosis, type, severity), prior and concomitant medications (as part of standard care of ATTR at eplontersen initiation), pre-existing and concurrent relevant morbidities will be described using descriptive statistics of counts, proportions and/or distribution characteristics (mean (SD), median (range)).	Quarter 2 2026- Quarter 1 2032
Long term safety with patients who initiated eplonersen treatment	Onset of new clinical events, abnormal laboratory values, serious adverse events will be analysed as follows: a) Counts and frequency of first events and total number of events, incidence rate and incidence risk of events per time periods (e.g., 0-6, 7-end of follow-up available at time of reporting). b) Cohort event monitoring analysis including a. Incidence densities per 6 months (in the first year) or 12-months (after one year) intervals will be estimated. b. Differences in incidence densities per 6 or 12months intervals c. Nelson-Aalen estimator of cumulative hazard rate function over time. c) For SAEs, qualitative case reports of clinical course and patients' characteristics and comorbidities will be provided. These outcomes are all relative to primary objective 2 of study and are all relative to the same outcome measure.	Quarter 2 2026- Quarter 1 2032

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Eplontersen treatment use	To describe eplontersen treatment use, including duration of treatment and reasons for discontinuation (overall, in patients with prior liver transplant, in patients with pre-existing severe hepatic impairment). These outcomes are all relative to secondary objective 1 of the study which is to describe "eplontersen treatment use".	Quarter 2 2026- Quarter 1 2032
Long-term safety in patients who initiate eplontersen treatment by subgroups	Same as primary objective 2, separately in i) patients with prior liver transplant and ii) patients with pre-existing severe hepatic impairment. These outcomes are relative to primary objective 2 of the study and to the same outcome measure, i.e. "long-term safety in patients who initiated eplontersen treatment". This is a long-term safety study without a prespecified adverse event of interest; therefore, all safety events are in scope, as defined in the protocol: all serious adverse events identified; other adverse events, including any new diagnosis reported as a co-morbidity, new sign or symptom, or new abnormal laboratory value within 115 days of last eplontersen dose. To support systematic and comprehensive listing of all AEs, clinical data in D8450R00003, in addition to serious adverse events, will be coded using MedDRA. Clinical data that cannot be mapped to MedDRA will also be considered.	Quarter 2 2026- Quarter 1 2032

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: ICON Clinical Research

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): January 29, 2032
• Study Completion (Estimated): January 29, 2032

Study Registration Dates

• First Submitted: May 19, 2026
• First Submitted That Met QC Criteria: June 11, 2026
• First Posted (Actual): June 17, 2026

Study Record Updates

• Last Update Posted (Actual): June 17, 2026
• Last Update Submitted That Met QC Criteria: June 11, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: ATTR, Transthyretin amyloidosis
• Additional Relevant MeSH Terms: Amyloidosis, Hereditary, Transthyretin-Related; Investigative Techniques; Methods; Observation
• Other Study ID Numbers: D8450R00022

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No