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
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
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
Parallel
ALN-HSD
DrugAdministered per the protocol
Placebo
DrugAdministered per the protocol
Change in quantitative liver Fibrosis (qFibrosis)
Change in the continuous qFibrosis score measured by second harmonic generation/two-photon excitation microscopy
Improvement of Non-Alcoholic Steatohepatitis Clinical Research Network (NASH-CRN) Fibrosis (F) stage by ≥1 stage without worsening of MASH on liver biopsy
Resolution of MASH with no worsening of NASH-CRN fibrosis on liver biopsy
Resolution of MASH (steatohepatitis) is defined as absent fatty liver disease or isolated or simple steatosis without steatohepatitis and a non-alcoholic fatty liver disease activity score (NAS) score of 0-1 for inflammation, 0 for ballooning, and any value for steatosis
Change in serum ALanine aminoTransferase (ALT)
Change in serum ASpartate aminoTransferase (AST)
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