Extension Study Assessing Long Term Safety and Efficacy of IONIS-TTR Rx in Familial Amyloid Polyneuropathy (FAP)

NCT ID: NCT02175004

Last Updated: 2023-11-18

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

135 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-06-26

Study Completion Date

2021-01-07

Brief Summary

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This study evaluates the safety and tolerability of extended dosing with IONIS-TTR Rx in patients with Familial Amyloid Polyneuropathy.

Detailed Description

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Familial Amyloid Polyneuropathy (FAP) is a rare, hereditary disease caused by mutations in the transthyretin (TTR) protein. TTR is made by the liver and secreted into the blood. TTR mutations cause it to misfold and deposit in multiple organs causing FAP.

IONIS-TTR Rx is an antisense drug that is designed to decrease the amount of mutant and normal TTR made by the liver. It is predicted that decreasing the amount of TTR protein will result in a decrease in the formation of TTR deposits, and thus slow or stop disease progression.

This study evaluates the safety and tolerability of extended dosing with IONIS-TTR Rx in patients with Familial Amyloid Polyneuropathy.

Conditions

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FAP Familial Amyloid Polyneuropathy TTR Transthyretin Amyloidosis

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Previous Placebo-Inotersen 300 mg

Participants received subcutaneous (SC) doses of 300 milligrams (mg) inotersen once weekly for up to 260 weeks. Participants who received inotersen-matching placebo in the previous study- ISIS 420915-CS2 (NCT01737398) were included in this group.

Group Type EXPERIMENTAL

Inotersen

Intervention Type DRUG

Inotersen SC

Previous Inotersen-Inotersen 300 mg

Participants received SC doses of 300 mg inotersen once weekly for up to 260 weeks. Participants who received inotersen in the previous study- ISIS 420915-CS2 were included in this group.

Group Type EXPERIMENTAL

Inotersen

Intervention Type DRUG

Inotersen SC

Interventions

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Inotersen

Inotersen SC

Intervention Type DRUG

Other Intervention Names

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TEGSEDI IONIS-TTR Rx ISIS 420915

Eligibility Criteria

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Inclusion Criteria

* Satisfactory completion of dosing \& efficacy assessments in ISIS 420915-CS2

Exclusion Criteria

* Any new condition or worsening of existing condition that could make the patient unsuitable for participation, or interfere with the patient participating in and/or completing the study
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ionis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of California, Irvine

Orange, California, United States

Site Status

Indiana University School of Medicine

Indianapolis, Indiana, United States

Site Status

Johns Hopkins University Bayview Medical Center

Baltimore, Maryland, United States

Site Status

Boston University School of Medicine - Amyloid Treatment & Research Program

Boston, Massachusetts, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Mount Sinai Medical Center

New York, New York, United States

Site Status

Columbia University Medical Center - The Neurological Institute

New York, New York, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, United States

Site Status

FLENI

Buenos Aires, , Argentina

Site Status

Federal University of Rio de Janeiro - University Hospital

Rio de Janeiro, , Brazil

Site Status

AACD

São Paulo, , Brazil

Site Status

CHU Henri Mondor - Department of Neurology

Créteil, , France

Site Status

CHU Bicetre Aphp French Referral Center for FAP/Cornamyl Network

Le Kremlin-Bicêtre, , France

Site Status

UKM; Universitätsklinikum Münster, Klinik für Transplantationsmedizin

Münster, , Germany

Site Status

Universita Degli Studi Di Messina - Azienda Ospedaliera Universitaria Policlinico "Gaetano Martino"

Messina, Sicily, Italy

Site Status

Centro per lo Studio e la Cura delle Amiloidosi Sistemiche - Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

Site Status

CHLN - Hospital de Santa Maria

Lisbon, , Portugal

Site Status

CHP-HGSA, Unidade Clinica de Paramiloidose

Porto, , Portugal

Site Status

Hospital Universitari Vall D' Hebron

Barcelona, , Spain

Site Status

Hospital Clinic

Barcelona, , Spain

Site Status

University College London - National Amyloidosis Centre

London, , United Kingdom

Site Status

Countries

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United States Argentina Brazil France Germany Italy Portugal Spain United Kingdom

References

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Brannagan TH, Coelho T, Wang AK, Polydefkis MJ, Dyck PJ, Berk JL, Drachman B, Gorevic P, Whelan C, Conceicao I, Plante-Bordeneuve V, Merlini G, Obici L, Plana JMC, Gamez J, Kristen AV, Mazzeo A, Gentile L, Narayana A, Olugemo K, Aquino P, Benson MD, Gertz M; NEURO-T. T. R. Open-Label Extension Investigators. Long-term efficacy and safety of inotersen for hereditary transthyretin amyloidosis: NEURO-TTR open-label extension 3-year update. J Neurol. 2022 Dec;269(12):6416-6427. doi: 10.1007/s00415-022-11276-8. Epub 2022 Jul 31.

Reference Type DERIVED
PMID: 35908242 (View on PubMed)

Karam C, Brown D, Yang M, Done N, Zhu JJ, Greatsinger A, Bozas A, Vera-Llonch M, Signorovitch J. Long-term treatment effects of inotersen on health-related quality of life in patients with hATTR amyloidosis with polyneuropathy: Analysis of the open-label extension of the NEURO-TTR trial. Muscle Nerve. 2022 Oct;66(4):438-446. doi: 10.1002/mus.27675. Epub 2022 Aug 4.

Reference Type DERIVED
PMID: 35799473 (View on PubMed)

Yarlas A, Lovley A, McCausland K, Brown D, Vera-Llonch M, Conceicao I, Karam C, Khella S, Obici L, Waddington-Cruz M. Early Data on Long-term Impact of Inotersen on Quality-of-Life in Patients with Hereditary Transthyretin Amyloidosis Polyneuropathy: Open-Label Extension of NEURO-TTR. Neurol Ther. 2021 Dec;10(2):865-886. doi: 10.1007/s40120-021-00268-x. Epub 2021 Aug 5.

Reference Type DERIVED
PMID: 34355354 (View on PubMed)

Brannagan TH, Wang AK, Coelho T, Waddington Cruz M, Polydefkis MJ, Dyck PJ, Plante-Bordeneuve V, Berk JL, Barroso F, Merlini G, Conceicao I, Hughes SG, Kwoh J, Jung SW, Guthrie S, Pollock M, Benson MD, Gertz M; NEURO-TTR open-label extension investigators. Early data on long-term efficacy and safety of inotersen in patients with hereditary transthyretin amyloidosis: a 2-year update from the open-label extension of the NEURO-TTR trial. Eur J Neurol. 2020 Aug;27(8):1374-1381. doi: 10.1111/ene.14285. Epub 2020 May 29.

Reference Type DERIVED
PMID: 32343462 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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2013-004561-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ISIS 420915-CS3

Identifier Type: -

Identifier Source: org_study_id

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