A Non-interventional Cohort Safety Study of Patients With hATTR-PN

Recruiting

• Conditions: Hereditary Transthyretin Amyloidosis With Polyneuropthy
• Interventions: Other: Data Collection

• Registration Number: NCT04850105
• Lead Sponsor: Akcea Therapeutics

Brief Summary

This is a prospective, non-interventional, Long-term, multinational cohort safety study of patients with Hereditary Transthyretin Amyloidosis with Polyneuropathy (hATTR-PN). The overarching goal of this study is to further characterize the long-term safety of TEGSEDI (inotersen) in patients with hATTR-PN under real-world conditions.

Detailed Description

Study Rationale:

hATTR-PN is an inherited, progressive, fatal disease caused by misfolded transthyretin (TTR) proteins that accumulate as amyloid fibrils predominantly in the peripheral nerves, heart, gastrointestinal tract, and other organs. hATTR-PN is a rare disease and there are no large epidemiological studies that reliably provide an indication of its prevalence. The worldwide distribution is unequal, with higher rates in Portugal, Japan, Brazil, Northern Sweden, and the US. Current estimates suggest there may be 10,000 afflicted patients worldwide.

TEGSEDI (inotersen) is an antisense oligonucleotide inhibitor of human TTR protein synthesis. In Europe and Canada, TEGSEDI is indicated for the treatment of Stage 1 or Stage 2 polyneuropathy in adult patients with hereditary transthyretin amyloidosis (hATTR). In the US, TEGSEDI is indicated for treatment of the polyneuropathy of hereditary TTR-mediated amyloidosis in adults. Efficacy has been demonstrated in patients with hATTR-PN, as reflected by a slowing or reversal of disease progression.

Research Question:

The overarching goal of this study is to further characterize the long-term safety of TEGSEDI in patients with hATTR-PN under real-world conditions.

Population:

Patients in Europe, US, and Canada will be enrolled from centers that manage patients with hATTR-PN. Physicians participating in the study will be instructed to invite all patients who meet study eligibility criteria to enroll until the enrollment period is closed.

Study Timeline

• Study First Submitted: 2021-04-06
• Study First Submitted QC: 2021-04-14
• Study First Posted: 2021-04-20
• Study Start: 2021-09-21
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-23
• Last Update Posted: 2025-04-24
• Primary Completion: 2036-03-31
• Study Completion: 2036-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

1. Either:

   1. TEGSEDI Exposed Cohort: Patients diagnosed with hATTR-PN who have taken any dose of TEGSEDI within 25 weeks prior to enrollment
   2. TEGSEDI Unexposed Cohort: Patients diagnosed with hATTR-PN who have not taken any dose of TEGSEDI within 25 weeks prior to enrollment and are eligible for TEGSEDI treatment per applicable product label

2. Clinically managed in Canada, Europe, or the US

3. Have provided appropriate written informed consent

Exclusion Criteria

• None

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
TEGSEDI-exposed cohort	Data Collection	This cohort consist of patients diagnosed with hATTR-PN who are receiving any dose of commercial TEGSEDI and who have provided written informed consent to be included into the study.
TEGSEDI-unexposed cohort	Data Collection	This cohort which will consist of patients diagnosed with hATTR-PN who have not taken any dose of TEGSEDI within 25 weeks prior to enrollment and are eligible for TEGSEDI treatment per applicable product label and who have provided written informed consent to be included into the study.

Primary Outcome Measures

Name	Time	Method
Further characterization of the long-term safety of TEGSEDI in patients with hATTR-PN under real-world conditions.	10 years	* Determination of the incidence rate of thrombocytopenia in patients with hATTR-PN treated with TEGSEDI (TEGSEDI-exposed cohort); * Comparison of the relative rates of thrombocytopenia in hATTR-PN patients treated with TEGSEDI (TEGSEDI exposed) to hATTR-PN patients unexposed to TEGSEDI (TEGSEDI- unexposed)

Secondary Outcome Measures

Name	Time	Method
Description of the incidence rate of the Adverse Events of Special Interest (AESI) in the TEGSEDI-exposed and TEGSEDI-unexposed patients.	10 years	To describe the incidence rate of the following Adverse Events of Special Interest (AESI): * severe thrombocytopenia; * serious and non-serious bleeding events; * glomerulonephritis; * composite of stroke and/or cervicocephalic arterial dissection; * central nervous system (CNS) vasculitis; * ocular toxicity due to vitamin A deficiency
Description of the time to onset of Adverse Events of Special Interest (AESI) in the TEGSEDI-exposed and TEGSEDI-unexposed patients.	10 years	To describe the time to onset of the following Adverse Events of Special Interest (AESI): * severe thrombocytopenia; * serious and non-serious bleeding events; * glomerulonephritis; * composite of stroke and/or cervicocephalic arterial dissection; * central nervous system (CNS) vasculitis; * ocular toxicity due to vitamin A deficiency

Trial Locations

Locations (2)

Study Centre; 🇪🇸 Madrid, Comunidad De Madrid, Spain

Study Center; 🇪🇸 Madrid, Spain