TRITON-PN: A Study to Evaluate the Efficacy and Safety of Nucresiran in Patients With Hereditary Transthyretin Amyloidosis With Polyneuropathy

Официальное название

TRITON-PN: A Phase 3, Global, Randomized, Open-Label Study to Evaluate the Efficacy and Safety of Nucresiran in Patients With Hereditary Transthyretin-Mediated Amyloidosis With Polyneuropathy (hATTR-PN)

Обзор

The purpose of this study is to: * Determine the efficacy of nucresiran in patients with hATTR-PN by evaluating the effect on neurologic impairment, quality of life, nutritional status, disability, and gait speed * Demonstrate superiority of nucresiran compared to in-study vutrisiran with respect to serum transthyretin (TTR) levels

Вмешательства

• Препарат Nucresiran
  Nucresiran 300 mg administered SC q6M
• Препарат Vutrisiran
  Vutrisiran 25 mg administered SC q3M

Первичные конечные точки

• Change from Baseline in the Modified Neuropathy Impairment Score +7 (mNIS+7) Compared to the External Placebo Group from the APOLLO Study (NCT01960348) at Month 9 [Срок оценки: Baseline and Month 9]

Вторичные конечные точки (10)

• Change from Baseline in Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Total Score Compared to the External Placebo Group from the APOLLO Study (NCT01960348) at Month 9 [Срок оценки: Baseline and Month 9]
• Percent Reduction in Serum TTR Levels in the Nucresiran Group Compared to the In-study Vutrisiran Group through Month 9 [Срок оценки: Up to Month 9]
• Change from Baseline in Modified Body Mass Index (mBMI) Compared to the External Placebo Group from the APOLLO Study (NCT01960348) at Month 9 [Срок оценки: Baseline and Month 9]
• Change from Baseline in the mNIS+7 Compared to the External Placebo Group from the APOLLO Study (NCT01960348) at Month 18 [Срок оценки: Baseline and Month 18]
• Change from Baseline in Norfolk QoL-DN Total Score Compared to the External Placebo Group from the APOLLO Study (NCT01960348) at Month 18 [Срок оценки: Baseline and Month 18]
• Change from Baseline in mBMI Compared to the External Placebo Group from the APOLLO Study (NCT01960348) at Month 18 [Срок оценки: Baseline and Month 18]
• Change from Baseline in Rasch-built Overall Disability Scale (R-ODS) Compared to the External Placebo Group from the APOLLO Study (NCT01960348) at Month 18 [Срок оценки: Baseline and Month 18]
• Change from Baseline in Timed 10-meter Walk Test (10-MWT) Compared to the External Placebo Group from the APOLLO Study (NCT01960348) at Month 18 [Срок оценки: Baseline and Month 18]
• Percent Reduction in Serum TTR Levels in the Nucresiran Group Compared to the In-study Vutrisiran Group through Month 18 [Срок оценки: Up to Month 18]
• Percent Reduction in Serum TTR Levels in the Nucresiran Group Compared to the In-study Vutrisiran Group at Week 6 [Срок оценки: Week 6]

Критерии участия

Критерии включения

• Has documented diagnosis of hATTR-PN
• Has a diagnosis of hATTR amyloidosis with polyneuropathy with a documented TTR gene variant
• Has a neuropathy impairment score (NIS) of 5 to 130 (inclusive)
• Has a Karnofsky Performance Status (KPS) of ≥60%

Критерии исключения

• Has had a liver transplant or is likely, in the opinion of the Investigator, to undergo liver transplantation during the Treatment Period of the study
• Has known other (non-hATTR) forms of amyloidosis or clinical evidence of leptomeningeal amyloidosis
• Has a New York Heart Association (NYHA) heart failure classification >2
• Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 upper limit of normal (ULN)
• Has total bilirubin >1.5 ULN
• Has estimated glomerular filtration rate (eGFR) ≤30 mL/min/1.73m\^2
• Has other known causes of sensorimotor or autonomic neuropathy

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 9 центров

• Clinical Trial Site — Aurora
• Clinical Trial Site — Chicago
• Clinical Trial Site — Baltimore
• Clinical Trial Site — Boston
• Clinical Trial Site — Rochester
• Clinical Trial Site — New York
• Clinical Trial Site — Chapel Hill
• Clinical Trial Site — Dallas
• … и ещё 1 центр

Италия · 4 центра

• Clinical Trial Site — Florence
• Clinical Trial Site — Milan
• Clinical Trial Site — Pavia
• Clinical Trial Site — Roma

Франция · 3 центра

• Clinical Trial Site — Créteil
• Clinical Trial Site — Le Kremlin-Bicêtre
• Clinical Trial Site — Marseille

Испания · 3 центра

• Clinical Trial Site — Barcelona
• Clinical Trial Site — Huelva
• Clinical Trial Site — L'Hospitalet de Llobregat

Тайвань · 3 центра

• Clinical Trial Site — Taipei
• Clinical Trial Site — Taipei
• Clinical Trial Site — Taoyuan City

Австралия · 2 центра

• Clinical Trial Site — Darlinghurst
• Clinical Trial Site — Woolloongabba

Бразилия · 2 центра

• Clinical Trial Site — Ribeirão Preto
• Clinical Trial Site — São Paulo

Германия · 2 центра

• Clinical Trial Site — Berlin
• Clinical Trial Site — Münster

Греция · 2 центра

• Clinical Trial Site — Athens
• Clinical Trial Site — Heraklion

Япония · 2 центра

• Clinical Trial Site — Kumamoto
• Clinical Trial Site — Suita

Португалия · 2 центра

• Clinical Trial Site — Lisbon
• Clinical Trial Site — Porto

South Korea · 2 центра

• Clinical Trial Site — Seoul
• Clinical Trial Site — Seoul

Швеция · 2 центра

• Clinical Trial Site — Stockholm
• Clinical Trial Site — Umeå

Cyprus · 1 центр

• Clinical Trial Site — Égkomi

Малайзия · 1 центр

• Clinical Trial Site — Kuala Lumpur

Turkey (Türkiye) · 1 центр

• Clinical Trial Site — Istanbul

Идентификаторы

NCT: NCT07223203 · ALN-TTRSC04-004 · 2025-522544-40-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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