A Precision Medicine Approach Using Gene Silencing to Treat a Chronic Liver Disease Called Metabolic Dysfunction-Associated Steatohepatitis (MASH) in Adult Participants at Increased Genetic Risk for This Condition

Официальное название

A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of siRNA Gene Silencing for the Treatment of Metabolic Dysfunction-Associated Steatohepatitis (MASH) in Participants With Genetic Risk Factors

Обзор

This study is researching an investigational drug, ALN-HSD called "study drug". This study is focused on participants who are known to have Metabolic dysfunction-Associated SteatoHepatitis (MASH). MASH is a form of Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD). MASH occurs when fat builds up in liver cells, damaging them, and making the liver inflamed and stiff from fibrosis (scar tissue). MASH can progress to cirrhosis (long term scarring) and liver failure (when the liver cannot perform its job). The aim of the study is to see the effect of the study drug on lessening liver scarring related to MASH. The study is looking at several other research questions, including: * How ALN-HSD works to improve liver function and lessen MASH-related inflammation in the liver * What side effects may happen from receiving the study drug * How much study drug and study drug metabolites (byproduct of the body breaking down the study drug) are in the blood at different times * Better understanding of the study drug and MASH

Вмешательства

• Препарат ALN-HSD
  Administered per the protocol
• Препарат Placebo
  Administered per the protocol

Первичные конечные точки

• Change in quantitative liver Fibrosis (qFibrosis) [Срок оценки: Baseline to week 52]

Вторичные конечные точки (12)

• Improvement of Non-Alcoholic Steatohepatitis Clinical Research Network (NASH-CRN) Fibrosis (F) stage by ≥1 stage without worsening of MASH on liver biopsy [Срок оценки: Baseline to week 52]
• Resolution of MASH with no worsening of NASH-CRN fibrosis on liver biopsy [Срок оценки: Baseline to week 52]
• Change in serum ALanine aminoTransferase (ALT) [Срок оценки: Baseline to week 52]
• Change in serum ASpartate aminoTransferase (AST) [Срок оценки: Baseline to week 52]
• Change in Enhanced Liver Fibrosis (ELF) [Срок оценки: Baseline to week 52]
• Change in N-terminal type III Collagen PROropeptide (PRO-C3) [Срок оценки: Baseline to week 52]
• Change in NIS4, a non-invasive fibrosis biomarker of NASH [Срок оценки: Baseline to week 52]
• Change in Fibrosis-4 (FIB-4) [Срок оценки: Baseline to week 52]
• Change in hepatic HydroxySteroiD 17β dehydrogenase 13 (HSD17B13) transcript level [Срок оценки: Baseline to week 52]
• Incidence of progression in qFibrosis on liver biopsy [Срок оценки: Baseline to week 52]
• Occurrence of Treatment-Emergent Adverse Events (TEAEs) [Срок оценки: Baseline to week 84]
• Severity of TEAEs [Срок оценки: Baseline to week 84]

Критерии участия

Критерии включения

• Adult male or female ≥18 years (or country's legal age of adulthood)
• A diagnosis of MASH with Fibrosis (F) stage 2 or 3, according to the NASH-CRN
• NAS score ≥3, as defined in the protocol
• Meets genotype criteria for study enrollment, as defined in the protocol
• Has a protocol defined FibroScan®-AST (FAST) score at screening or within approximately 12 weeks of screening

Критерии исключения

• Evidence of other forms of known chronic liver disease, as defined in the protocol
• Known history of alcohol or other substance abuse within the last year or at any time during screening, as defined in the protocol
• History of Type 1 diabetes
• Bariatric surgery within approximately 5 years prior to or planned during the study period
• Prior exposure to any investigational drug targeting HSD17B13 or patatin-like phospholipase domain containing 3 (PNPLA3) (eg, ALN-HSD, ARO-HSD, ALN-PNP, AZD2693)

Note: Other protocol-defined Inclusion/Exclusion Criteria apply

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

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 61 центр

• Arizona Liver Health — Chandler
• The Institute for Liver Health II LLC DBA Arizona Clinical Trials - Flagstaff — Flagstaff
• The Institute for Liver Health II LLC DBA Arizona Liver Health - Peoria — Peoria
• Adobe Clinical Research — Tucson
• Arizona Liver Health - Tucson — Tucson
• Del Sol Research Management, LLC — Tucson
• San Fernando Valley Health Institute — Canoga Park
• Velocity Clinical Research — Chula Vista
• … и ещё 53 центра

South Korea · 5 центров

• Seoul National University Bundang Hospital — Seongnam-si
• Pusan National University Hospital — Busan
• Kyungpook National University Hospital — Daegu
• Keimyung University Dongsan Hospital — Daegu
• Hanyang University Seoul Hospital — Seoul

Пуэрто-Рико · 4 центра

• Isis Clinical Research Center — Guaynabo
• Klinical Investigations — San Juan
• Latin Clinical Trial Center — San Juan
• Fundacion de Investigacion (FDI) Clinical Research — San Juan

Япония · 1 центр

• JCHO Hokkaido Hospital — Sapporo

Идентификаторы

NCT: NCT05519475 · ALN-HSD-NASH-2130

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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