NEURO-TTRansform: A Study to Evaluate the Efficacy and Safety of Eplontersen (Formerly Known as ION-682884, IONIS-TTR-LRx and AKCEA-TTR-LRx) in Participants With Hereditary Transthyretin-Mediated Amyloid Polyneuropathy
NCT ID: NCT04136184
Last Updated: 2024-12-13
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
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COMPLETED
PHASE3
168 participants
INTERVENTIONAL
2019-12-11
2023-07-12
Brief Summary
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Detailed Description
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Conditions
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Keywords
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Study Design
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RANDOMIZED
CROSSOVER
TREATMENT
NONE
Study Groups
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Inotersen
Participants received inotersen, 300 milligrams (mg), subcutaneously (SC), once weekly up to Week 34. After Week 35 assessment, participants received eplontersen, 45 mg, SC, once every 4 weeks starting from Week 37 up to Week 81.
Inotersen
Inotersen by subcutaneous injection
Eplontersen
Eplontersen by subcutaneous injection
Eplontersen
Participants received eplontersen, 45 mg, SC, once every 4 weeks up to Week 81.
Eplontersen
Eplontersen by subcutaneous injection
Interventions
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Inotersen
Inotersen by subcutaneous injection
Eplontersen
Eplontersen by subcutaneous injection
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal or abstinent
3. Males must be surgically sterile or, abstinent or, if engaged in sexual relations with a woman of child-bearing potential, the participant or the participantss non-pregnant female partner must be using a highly effective contraceptive method
4. Diagnosis of hereditary transthyretin-mediated polyneuropathy as defined by meeting all 3 of the following:
* Stage 1 or Stage 2 Familial Amyloid Polyneuropathy (FAP) or Coutinho Stage
* Documented genetic mutation in the TTR gene
* Symptoms and signs consistent with neuropathy associated with transthyretin amyloidosis, including Neuropathy Impairment Score (NIS) ≥ 10 and ≤ 130
Exclusion Criteria
2. Karnofsky performance status ≤ 50
3. Other causes of sensorimotor or autonomic neuropathy (e.g., autoimmune disease), including uncontrolled diabetes
4. Prior liver transplant or anticipated liver transplant within 1-yr of Screening
5. New York Heart Association (NYHA) functional classification of ≥ 3
6. Acute coronary syndrome within 6 months of screening or major surgery within 3 months of Screening
7. Other types of amyloidosis
8. Have any other conditions, which, in the opinion of the Investigator or Sponsor would make the participant unsuitable for inclusion, or could interfere with the participant participating in or completing the Study
9. Current treatment with any approved drug for hereditary TTR amyloidosis such as Vyndaqel® / Vyndamax™ (tafamidis), Tegsedi™ (inotersen), Onpattro™ (patisiran), off-label use of diflunisal or doxycycline, and tauroursodeoxycholic acid (TUDCA). If previously treated with Vyndaqel® / Vyndamax™, diflunisal or doxycycline, and TUDCA, must have discontinued treatment for at least 2 weeks prior to Study Day 1
10. Previous treatment with Tegsedi™ (Inotersen) or Onpattro™ (patisiran), or other oligonucleotide or RNA therapeutic (including siRNA)
18 Years
82 Years
ALL
No
Sponsors
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Ionis Pharmaceuticals, Inc.
INDUSTRY
Responsible Party
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Locations
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Mayo Clinic - Arizona
Scottsdale, Arizona, United States
Mayo Clinic - Jacksonville
Jacksonville, Florida, United States
Indiana University School of Medicine - Indianapolis
Indianapolis, Indiana, United States
University of Kansas Medical Center
Kansas City, Kansas, United States
Johns Hopkins University Neurology Research Office
Baltimore, Maryland, United States
Boston University School of Medicine
Boston, Massachusetts, United States
Mayo Clinic - Rochester
Rochester, Minnesota, United States
The Neurological Institute of New York
New York, New York, United States
University of North Carolina Hospitals - Neurology Clinic
Chapel Hill, North Carolina, United States
Oregon Health and Science University
Portland, Oregon, United States
Penn Presbyterian Medical Center
Philadelphia, Pennsylvania, United States
University of Washington Medical Center
Seattle, Washington, United States
Hospital Italiano de Buenos Aires
Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina
Hospital El Cruce
San Juan Bautista, Buenos Aires, Argentina
STAT Research
Buenos Aires, , Argentina
Instituto Fleni
Buenos Aires, , Argentina
Perron Institute for Neurological and Translational Science
Nedlands, Western Australia, Australia
Instituto de Neurologia de Curitiba
Curitiba, Paraná, Brazil
Universidade Estadual de Campinas
Campinas, , Brazil
Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto
Ribeirão Preto, , Brazil
Hospital Universitário Clementino Fraga Filho
Rio de Janeiro, , Brazil
Associação de Assistência à Criança Deficiente - Unidade Lar Escola
São Paulo, , Brazil
Toronto General Hospital
Toronto, Ontario, Canada
The Cyprus Institute of Neurology and Genetics
Égkomi, , Cyprus
Centre Hospitalier Universitaire de Toulouse
Toulouse, Haute-Garonne, France
Hôpital de la Timone
Marseille, , France
Hôpital Bicêtre
Le Kremlin-Bicêtre, Île-de-France Region, France
Universitätsklinikum Würzburg
Würzburg, Bavaria, Germany
Universitätsklinikum Heidelberg
Heidelberg, , Germany
University General Hospital of Heraklion (PAGNI)
Heraklion, Crete, Greece
Azienda Ospedaliera Universitaria Policlinico Gaetano Martino
Messina, , Italy
Fondazione IRCCS Istituto Neurologico Carlo Besta
Milan, , Italy
Fondazione IRCCS Policlinico San Matteo
Pavia, , Italy
Fondazione Policlinico Universitario Agostino Gemelli
Roma, , Italy
Auckland City Hospital
Grafton, Auckland, New Zealand
Centro Hospitalar Universitário Lisboa Norte - Hospital De Santa Maria
Lisbon, , Portugal
Centro Hospitalar Universitário do Porto - Hospital Geral de Santo Antonio
Porto, , Portugal
Hospital Son Llàtzer
Palma de Mallorca, Balearic Islands, Spain
Hospital Clínico San Carlos
Madrid, , Spain
Norrlands Universitetssjukhus
Umeå, , Sweden
Chang Gung Memorial Hospital - Linkou Branch
Taoyuan, Guishan District, Taiwan
China Medical University Hospital
Taichung, Taichung, Taiwan
Taipei Veterans General Hospital
Taipei City, Taipei, Taiwan
National Taiwan University Hospital
Taipei, , Taiwan
İstanbul Üniversitesi - Istanbul Tıp Fakültesi
Istanbul, , Turkey (Türkiye)
Countries
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References
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Coelho T, Marques W Jr, Dasgupta NR, Chao CC, Parman Y, Franca MC Jr, Guo YC, Wixner J, Ro LS, Calandra CR, Kowacs PA, Berk JL, Obici L, Barroso FA, Weiler M, Conceicao I, Jung SW, Buchele G, Brambatti M, Chen J, Hughes SG, Schneider E, Viney NJ, Masri A, Gertz MR, Ando Y, Gillmore JD, Khella S, Dyck PJB, Waddington Cruz M; NEURO-TTRansform Investigators. Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy. JAMA. 2023 Oct 17;330(15):1448-1458. doi: 10.1001/jama.2023.18688.
Coelho T, Waddington Cruz M, Chao CC, Parman Y, Wixner J, Weiler M, Barroso FA, Dasgupta NR, Jung SW, Schneider E, Viney NJ, Dyck PJB, Ando Y, Gillmore JD, Khella S, Gertz MA, Obici L, Berk JL. Characteristics of Patients with Hereditary Transthyretin Amyloidosis-Polyneuropathy (ATTRv-PN) in NEURO-TTRansform, an Open-label Phase 3 Study of Eplontersen. Neurol Ther. 2023 Feb;12(1):267-287. doi: 10.1007/s40120-022-00414-z. Epub 2022 Dec 16.
Coelho T, Ando Y, Benson MD, Berk JL, Waddington-Cruz M, Dyck PJ, Gillmore JD, Khella SL, Litchy WJ, Obici L, Monteiro C, Tai LJ, Viney NJ, Buchele G, Brambatti M, Jung SW, St L O'Dea L, Tsimikas S, Schneider E, Geary RS, Monia BP, Gertz M. Design and Rationale of the Global Phase 3 NEURO-TTRansform Study of Antisense Oligonucleotide AKCEA-TTR-LRx (ION-682884-CS3) in Hereditary Transthyretin-Mediated Amyloid Polyneuropathy. Neurol Ther. 2021 Jun;10(1):375-389. doi: 10.1007/s40120-021-00235-6. Epub 2021 Feb 26.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
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2019-001698-10
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
ION-682884-CS3
Identifier Type: -
Identifier Source: org_study_id