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

A Prospective, Non-interventional, Long-term, Multinational Cohort Safety Study of Patients With Hereditary Transthyretin Amyloidosis With Polyneuropathy (hATTR-PN)

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.

Study Overview

• Status: Recruiting
• Conditions: Hereditary Transthyretin Amyloidosis With Polyneuropthy
• Intervention / Treatment: Other: Data Collection

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 Type: Observational
• Enrollment (Estimated): 240

Contacts and Locations

• Study Contact: Name: Ionis Pharmaceuticals; Phone Number: (844) 915-5145; Email: ionisNCT04850105study@clinicaltrialmedia.com

Study Locations

• Canada
  • Toronto, Canada, ON M2K 0A6
    • Recruiting
    • Study Center
• France
  • Saint-Herblain, France, 44093
    • Recruiting
    • Study Centre
  • Cedex
    • Lille, Cedex, France, 59037
      • Recruiting
      • Study Center
  • Romaine
    • Nice, Romaine, France, 06001
      • Recruiting
      • Study Center
• Germany
  • Heidelberg, Germany, 69120
    • Recruiting
    • Study Center
• Greece
  • Athens, Greece, 115 28
    • Recruiting
    • Study Center
  • Athens, Greece, 11528
    • Recruiting
    • Study Center
  • Heraklion, Greece, 71500
    • Recruiting
    • Study Center
• Italy
  • Bologna, Italy, 40139
    • Recruiting
    • Study Center
  • Genova, Italy, 16132
    • Recruiting
    • Study Center
  • Messina, Italy, 98125
    • Recruiting
    • Study Center
  • Milano, Italy, 20133
    • Recruiting
    • Study Center
  • Napoli, Italy, 80131
    • Recruiting
    • Study Center
  • Pavia, Italy, 27100
    • Recruiting
    • Study Center
  • Roma, Italy, 00173
    • Recruiting
    • Study Center
  • Roma
    • Lagosanto, Roma, Italy, 00168
      • Recruiting
      • Study Center
  • Rome
    • Roma, Rome, Italy, 00189
      • Recruiting
      • Study Centre
• Portugal
  • Lisboa, Portugal, 1649 035
    • Recruiting
    • Study Center
• Spain
  • Madrid, Spain, 28041
    • Recruiting
    • Study Center
  • Andalucia
    • Huelva, Andalucia, Spain, 21005
      • Recruiting
      • Study Center
  • Avenida De Roma
    • Oviedo, Avenida De Roma, Spain, 33011
      • Recruiting
      • Study Centre
  • Barcelona
    • Villarreal, Barcelona, Spain, 08036
      • Recruiting
      • Study Centre
  • Cataluna
    • Barcelona, Cataluna, Spain, 08035
      • Recruiting
      • Study Centre
  • Comunidad De Madrid
    • Madrid, Comunidad De Madrid, Spain, 28040
      • Recruiting
      • Study Centre
  • Islas Baleares
    • Palma De Mallorca, Islas Baleares, Spain, 07198
      • Recruiting
      • Study Center
• United States
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Recruiting
      • Study Center
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • Study Center
    • Los Angeles, California, United States, 90073
      • Recruiting
      • Study Center
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Recruiting
      • Study Center
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Recruiting
      • Study Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • Study Centre
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Study Center
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Study Center
    • Rosedale, New York, United States, 11422
      • Recruiting
      • Study Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Study Center
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Recruiting
      • Study Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Study Center
  • Texas
    • Dallas, Texas, United States, 75204
      • Recruiting
      • Study Center
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Recruiting
      • Study Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The TEGSEDI-exposed cohort will consist of patients diagnosed with hATTR-PN who are receiving TEGSEDI. Data from the TEGSEDI-exposed cohort will be compared to data collected prospectively from a TEGSEDI-unexposed 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.

Patients in Europe, US, and Canada will be enrolled from centers that manage patients with hATTR-PN.

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
TEGSEDI-exposed cohort; 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.	Other: Data Collection; Data on each patient will be collected at study enrollment and at each follow-up visit. No mandatory visits, tests, or assessments are required for this study. All visits will be scheduled and conducted according to the clinical site's normal clinical practice.
TEGSEDI-unexposed cohort; 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.	Other: Data Collection; Data on each patient will be collected at study enrollment and at each follow-up visit. No mandatory visits, tests, or assessments are required for this study. All visits will be scheduled and conducted according to the clinical site's normal clinical practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Further characterization of the long-term safety of TEGSEDI in patients with hATTR-PN under real-world conditions.	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)	10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Description of the incidence rate of the Adverse Events of Special Interest (AESI) in the TEGSEDI-exposed and TEGSEDI-unexposed patients.	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	10 years
Description of the time to onset of Adverse Events of Special Interest (AESI) in the TEGSEDI-exposed and TEGSEDI-unexposed patients.	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	10 years

Collaborators and Investigators

• Sponsor: Akcea Therapeutics
• Collaborators: United BioSource, LLC

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2021
• Primary Completion (Estimated): March 31, 2036
• Study Completion (Estimated): March 31, 2036

Study Registration Dates

• First Submitted: April 6, 2021
• First Submitted That Met QC Criteria: April 14, 2021
• First Posted (Actual): April 20, 2021

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Amyloidosis; Hereditary Transthyretin Amyloidosis; hATTR-PN; hATTR
• Additional Relevant MeSH Terms: Metabolic Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Neuromuscular Diseases; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Proteostasis Deficiencies; Metabolism, Inborn Errors; Heredodegenerative Disorders, Nervous System; Amyloidosis, Familial; Amyloid Neuropathies; Amyloidosis; Amyloid Neuropathies, Familial
• Other Study ID Numbers: TEG4001; EUPAS37728 (Other Identifier: EU PAS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No