Transthyretin Amyloidosis
Conditions
Keywords
Eplontersen, pregnancy, Wainua, Wainzua
Brief summary
The overall objective of this DPSS is to describe the occurrence of pregnancy and maternal complications, adverse effects on the developing fetus and neonate, and adverse effects on the infant associated with exposure to eplontersen during pregnancy and/or lactation.
Detailed description
Currently, there are no clinical studies of eplontersen use in pregnant individuals. Although it is expected that exposure to eplontersen during pregnancy or lactation is very rare, it is important to capture as many exposed cases as possible. This descriptive pregnancy safety study (DPSS) will add to the current body of knowledge regarding the safety of eplontersen exposure during pregnancy and lactation and maternal, fetal, and infant outcomes following exposure to eplontersen. The study is designed to fulfill health authorities' post-marketing requirements. This DPSS will analyze secondary data on cases of eplontersen-exposed pregnant and lactating individuals collected through a PRegnancy outcomes Intensive Monitoring (PRIM) enhanced pharmacovigilance (PV) approach utilizing AstraZeneca's PV Global Safety Database (PV-Argus). Data sources: All eplontersen-exposed cases reported to AstraZeneca PV-Argus as notifiable events related to pregnancy and lactation; and cases reported from clinical trials, spontaneous post-marketing reports, post-marketing observational studies, patient-oriented programs, published literature, and personal communication by healthcare providers will be eligible for inclusion in the analysis. Data on eplontersen-exposed cases will be captured and processed using a pre-specified follow-up schedule and questionnaires. In case of missing data, there will be several attempts to collect data using all contact methods supplied by the reporters at the time of initial report. Study size: This DPSS is descriptive in nature, and a formal sample size calculation is not performed. Feasibility calculations indicate that the DPSS may capture five exposed pregnancies over the study period. Data analysis: Analyses will be conducted in accordance with the study objectives, table/listing shells, and applicable guidelines. Demographics, medical and obstetric history, and disease characteristics will be summarized using descriptive statistics. The outcomes will be reported as a proportion and 95% confidence interval (if applicable) and calculated by dividing the number of cases of the outcome by the appropriate denominator for the particular outcome. If fewer than ten cases are reported, formal analyses will not be performed, and reporting will be limited to case narratives.
Interventions
None listed
Sponsors
AstraZeneca
ICON plc
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* all pregnancy and/or lactation cases with exposure to eplontersen and a diagnosis of an approved indication for treatment with eplontersen * all adverse event reports in infants in the first 12 months of age that are or can be linked to pregnancy or lactation reports in individuals previously diagnosed with an approved indication and exposed to eplontersen during pregnancy or lactaction
Exclusion criteria
* all case reports considered invalid (i.e. minimum data is not provided at first report nor follow-up), or where reporter indicates that they do not wish to be contacted to obtain follow-up information, or the reporter/patient cannot be identified
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major congenital malformations | November 2025 - December 2035 | All major congenital malformations diagnosed in utero, at birth or during the the first year of life. Considering the small number of patients anticipated to be included in this study, it is possible that only case narratives will be developed. However, if at least ten exposed pregnancies are reported, the data will be summarized quantitatively, using relevant measures. Major congenital malformation will be reported as numbers and proportions. When presented, the 95% confidence intervals (CIs) for proportion of the outcome of interest will be constructed using the exact (Clopper-Pearson) method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| composite outcome of pregnancy and infant adverse outcomes ( except major congenital malformation | November 2025-December 2035 | pregnancy complications, spontaneous abortion, stillbirth, induced abortion, preterm birth, small for gestational age, postnatal growth deficiencies, infant development delay, neonatal mortality, infant mortality, as well as any other infant adverse events |
Countries
Germany
Contacts
CONTACTAstraZeneca Clinical Study Information Center
PRINCIPAL_INVESTIGATORMyriam Alexander, PHD
AstraZeneca
Outcome results
None listed