A cohort event monitoring study to characterise 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)

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  WAINZUA
• Study drug International non-proprietary name (INN) or common name:
  EPLONTERSEN SODIUM
• Anatomical Therapeutic Chemical (ATC) code:
  (N07XX21) eplontersen

  eplontersen
• Medical condition to be studied:
  Cardiac amyloidosis

  Familial amyloidosis

Population studied

• Short description of the study population:
  The NCT06465810 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 NCT06465810 cohort who meet the additional criteria below.; Inclusion Criteria:; 1. NCT06465810 participants who consented to have their data used for future related research studies. ; 2. NCT06465810 participants who initiated eplontersen treatment up to 1-year prior to enrolment into NCT06465810 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 NCT06465810 study observation period will be included.; Exclusion criteria:; 1. Patients with exposure to eplontersen more than 1-year prior to enrolment into NCT06465810 study.; 2. Patients who participated in an interventional ATTR study in the 12-months prior to enrolment into NCT06465810 study.
• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)
• Special population of interest:
  Hepatic impaired
• Special population of interest, other:
  Prior liver transplant

Study design details

• Study design:
  The sTTRing study is a retrospective observational cohort study and analyses of patients initiating eplontersen in the real-world, combining data from several different data sources.
• Main study objective:
  The primary objectives of the study are as follows: ; 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. ; The secondary objectives of the study are as follows:; 1.To describe eplontersen treatment use, including duration of treatment and reasons for discontinuation, overall and by sub-populations of individualswith prior liver transplant or individuals with pre-existing severe hepatic impairment. ; 2.To describe the incidence of safety events occurring in patients who initiate eplontersen treatment, including onset of new clinical events, abnormal laboratory values and serious adverse events separately i) in patients with prior liver transplant, overall and by reason for liver transplant, if feasible; and ii) in patients with pre-existing severe hepatic impairment
• Setting:
  The D8450R00003 study cohort includes individuals with confirmed diagnosis of ATTR , aged ≥18 years at the time of providing the informed consent. The overall sTTRing study population will be a subset of the D8450R00003 cohort who meet the additional inclusion criteria belowThe sTTRing study cohort will include those who meet the following additional 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 or during the D8450R00003 study observation period, irrespective of ATTR phenotype or genotype. For the comparative analyses, patients unexposed to eplontersen treatment and who initiated other ATTR treatments during D8450R00003 study observation period will be included. ; The sTTRing study cohort will exclude those to whom the following additional exclusion criteria apply:; 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.
• Comparators:
  If feasible, a comparator cohort of non-eplontersen exposed patients who initiated another ATTR treatment will be identified and matched eplontersen initiators to achieve balance, and comparative analyses will be performed to evaluate long-term safety of eplontersen relative to other treatments.
• Outcomes:
  1. The prevalence of liver transplant prior to eplontersen initiation (overall and by reason for liver transplant) ; 2. The prevalence of severe hepatic impairment at eplontersen initiation ; 3. Demographic and clinical characteristics (Laboratory markers, Clinical ATTR characteristics, Comorbidities, concomitant Medications, comorbidities. ; 4. ATTR Treatment details; 5. Safety endpoints ; 6. Total duration of follow-up (person time observed)
• Data analysis plan:
  The analysis will be descriptive in nature using descriptive statistics of counts, frequency, proportion and/or distribution characteristics (mean (SD), median (range)). Where possible, these characteristics will be described separately in new and prior eplontersen users; overall and by subgroups of interest, i.e., patients with prior liver transplant and patients with severe hepatic impairment at eplontersen initiation. Cohort event monitoring analysis will be performed to identify adverse events that require further characterisation including incidence densities and differences in incidence densities. If feasible, long-term safety of eplontersen will be compared to other treatments. An adequately balanced group of patients unexposed to eplontersen and new users of other ATTR treatments will be matched to patients initiating eplontersen treatment using propensity score matching methodology
• Summary results:
  Not applicable