NCT05519475: NASHGEN-2

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

Recruiting now Phase 2 Last updated 3 February 2026

What this trial tests

Phase 2 trial testing ALN-HSD in Metabolic Dysfunction-associated Steatohepatitis (MASH) in 90 participants. Currently enrolling.

Timeline

9 February 2023

Primary endpoint
8 September 2027

8 September 2027

Quick facts

Lead sponsor	Regeneron Pharmaceuticals
Phase	Phase 2
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	90
Start date	9 February 2023
Primary completion	8 September 2027
Estimated completion	8 September 2027
Sites	71 locations across Japan, United States, Puerto Rico, South Korea

Drugs / interventions tested

• ALN-HSD — full drug profile →
• Placebo

Conditions studied

• Metabolic Dysfunction-associated Steatohepatitis (MASH) — all drugs for Metabolic Dysfunction-associated Steatohepatitis (MASH) →

Sponsor

Regeneron Pharmaceuticals — full company profile →

Who can join

Adults 18 to 75, any sex, with Metabolic Dysfunction-associated Steatohepatitis (MASH). Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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 side effects 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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Nucleic acid drugs: recent progress and future perspectives.
   Sun X, Setrerrahmane S, Li C, Hu J, et al · · 2024 · cited 72× · PMID 39609384 · DOI 10.1038/s41392-024-02035-4
2. Landscape of small nucleic acid therapeutics: moving from the bench to the clinic as next-generation medicines.
   Liu M, Wang Y, Zhang Y, Hu D, et al · · 2025 · cited 62× · PMID 40059188 · DOI 10.1038/s41392-024-02112-8
3. Genetics of Metabolic Dysfunction-associated Steatotic Liver Disease: The State of the Art Update.
   Sookoian S, Rotman Y, Valenti L. · · 2024 · cited 43× · PMID 39094912 · DOI 10.1016/j.cgh.2024.05.052
4. Hepatocyte targeting <i>via</i> the asialoglycoprotein receptor.
   Ramírez-Cortés F, Ménová P. · · 2025 · cited 22× · PMID 39628900 · DOI 10.1039/d4md00652f
5. MetALD: Does it require a different therapeutic option?
   Marek GW, Malhi H. · · 2024 · cited 21× · PMID 38820071 · DOI 10.1097/hep.0000000000000935
6. Recent Update on siRNA Therapeutics.
   Ebenezer O, Oyebamiji AK, Olanlokun JO, Tuszynski JA, et al · · 2025 · cited 19× · PMID 40331977 · DOI 10.3390/ijms26083456
7. Oligonucleotide therapies for nonalcoholic steatohepatitis.
   Li S, Xiong F, Zhang S, Liu J, et al · · 2024 · cited 19× · PMID 38665220 · DOI 10.1016/j.omtn.2024.102184
8. Precision medicine and nucleotide-based therapeutics to treat steatotic liver disease.
   Caddeo A, Romeo S. · · 2025 · cited 17× · PMID 39103998 · DOI 10.3350/cmh.2024.0438