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
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: ALN-HSD, Placebo.
- Who it may be relevant to
- Registry conditions: Metabolic Dysfunction-Associated SteatoHepatitis (MASH). Basic parameters: 18 years — 75 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States, Japan, Puerto Rico, South Korea
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
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
Overview
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
Interventions
- Drug ALN-HSD
Administered per the protocol - Drug Placebo
Administered per the protocol
Primary outcome measures
- Change in quantitative liver Fibrosis (qFibrosis) [Time frame: Baseline to week 52]
Secondary outcome measures (12)
- Improvement of Non-Alcoholic Steatohepatitis Clinical Research Network (NASH-CRN) Fibrosis (F) stage by ≥1 stage without worsening of MASH on liver biopsy [Time frame: Baseline to week 52]
- Resolution of MASH with no worsening of NASH-CRN fibrosis on liver biopsy [Time frame: Baseline to week 52]
- Change in serum ALanine aminoTransferase (ALT) [Time frame: Baseline to week 52]
- Change in serum ASpartate aminoTransferase (AST) [Time frame: Baseline to week 52]
- Change in Enhanced Liver Fibrosis (ELF) [Time frame: Baseline to week 52]
- Change in N-terminal type III Collagen PROropeptide (PRO-C3) [Time frame: Baseline to week 52]
- Change in NIS4, a non-invasive fibrosis biomarker of NASH [Time frame: Baseline to week 52]
- Change in Fibrosis-4 (FIB-4) [Time frame: Baseline to week 52]
- Change in hepatic HydroxySteroiD 17β dehydrogenase 13 (HSD17B13) transcript level [Time frame: Baseline to week 52]
- Incidence of progression in qFibrosis on liver biopsy [Time frame: Baseline to week 52]
- Occurrence of Treatment-Emergent Adverse Events (TEAEs) [Time frame: Baseline to week 84]
- Severity of TEAEs [Time frame: Baseline to week 84]
Eligibility criteria
Inclusion criteria
- 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
Exclusion criteria
- 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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Quadruple blind
- Primary purpose
- Treatment
Study locations
United States · 61 centers
- 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
- … and 53 more centers
South Korea · 5 centers
- 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
Puerto Rico · 4 centers
- Isis Clinical Research Center — Guaynabo
- Klinical Investigations — San Juan
- Latin Clinical Trial Center — San Juan
- Fundacion de Investigacion (FDI) Clinical Research — San Juan
Japan · 1 center
- JCHO Hokkaido Hospital — Sapporo
Identifiers
NCT: NCT05519475 · ALN-HSD-NASH-2130