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:
- 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).
- To describe long-term safety in patients who initiate eplontersen treatment, including onset of new clinical events, abnormal laboratory values and serious adverse events.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
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.
Tipo de estudo
Inscrição (Estimado)
Contactos e Locais
Contato de estudo
- Nome: AstraZeneca Clinical Study Information Center
- Número de telefone: 1-877-240-9479
- E-mail: information.center@astrazeneca.com
Locais de estudo
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Hanover, Alemanha
- Recrutamento
- Research Site
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British Columbia
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Vancouver, British Columbia, Canadá, V6Z 1Y6
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- Research Site
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Beijing, China
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- Research Site
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Majadahonda, Espanha
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- Research Site
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California
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Los Angeles, California, Estados Unidos, 90095
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- Research Site
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Birmingham, Reino Unido
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- Research Site
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Método de amostragem
População do estudo
Descrição
Inclusion Criteria:
- D8450R00003 participants who consented to have their data used for future related research studies.
- 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:
- Patients with exposure to eplontersen more than 1-year prior to enrolment into D8450R00003 study.
- Patients who participated in an interventional ATTR study in the 12-months prior to enrolment into D8450R00003 study.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
Coortes e Intervenções
Grupo / Coorte |
Intervenção / Tratamento |
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Eplontersen users
D8450R00003 population of new and prior eplontersen users (including prior liver transplant and severe hepatic impairment subpopulations)
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Not applicable this is observational study no intervention is planned.
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
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Demographic and clinical characteristics of eplontersen users, including the prevalence of prior liver transplant and severe hepatic impairment
Prazo: Quarter 2 2026- Quarter 1 2032
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Quarter 2 2026- Quarter 1 2032
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Long term safety with patients who initiated eplonersen treatment
Prazo: Quarter 2 2026- Quarter 1 2032
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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
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
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Eplontersen treatment use
Prazo: Quarter 2 2026- Quarter 1 2032
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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".
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Quarter 2 2026- Quarter 1 2032
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Long-term safety in patients who initiate eplontersen treatment by subgroups
Prazo: Quarter 2 2026- Quarter 1 2032
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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.
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Quarter 2 2026- Quarter 1 2032
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- D8450R00022
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