A Master Protocol of Randomized, Double-Blind, Placebo-Controlled, Phase 2 Studies of siRNA Gene Silencing for the Treatment of Non- Alcoholic Steatohepatitis (NASH) in Participants With Genetic Risk Factors

Study of Investigational Treatment for Non-Alcoholic Steatohepatitis (NASH)

Primary Investigator
N
Niharika Samala, MD

Primary Investigator

Enrolling By Invitation
18 years - 75 years
All
Phase 2
5 participants needed
2 Locations

Brief description of study

The study is researching an investigational drug called ALN-HSD (called "study drug" in this form). The study is focused on participants who are known to have non-alcoholic steatohepatitis (NASH). NASH is a form of non-alcoholic fatty liver disease (NAFLD). NASH occurs when fat builds up in liver cells, damaging them, and making the liver inflamed and stiff from fibrosis (scar tissue). NASH can progress to cirrhosis (long term scarring) and liver failure (when your 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 NASH.

The study is looking at several other research questions, including:

  • How ALN-HSD works to improve liver function and lessen NASH 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 your blood at different times

  • Better understanding of the study drug and NASH

Detailed description of study

Participants with NASH and F2 or F3 fibrosis and non-alcoholic fatty liver disease (NAFLD) activity score (NAS) ≥4 will be randomized 2:1:2 to receive placebo, 25 mg ALN-HSD, or 400 mg ALN-HSD, respectively, administered by subcutaneous (SC) injection every 4 weeks (Q4W) for a total of 13 doses.

 

The duration of the study for a participant is up to approximately 100 weeks, including the screening period.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Metabolic Dysfunction Associated Steatohepatitis, MASH, Non-alcoholic Steatohepatitis, NASH
  • Age: 18 years - 75 years
  • Gender: All

Inclusion Criteria:

  •  A diagnosis of NASH with fibrosis (F) stage 2 or 3

  •  NAS score ≥4 according to the NASH CRN histological scoring system

  •  Meets genotype criteria for study enrollment in either Study 1 or Study 2, as defined in the protocol

  •  A Vibration-Controlled Transient Elastography (VCTE) liver stiffness measurement, as defined in the protocol

Exclusion Criteria:

  • Evidence of other forms of known chronic liver disease
  • Known history of alcohol or other substance abuse within the last year
  • 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 PNPLA3 (eg, ALNHSD or ARO-HSD, AZD2693)

This study investigates a treatment for Non-Alcoholic Steatohepatitis (NASH), a liver condition where fat builds up in the liver, causing damage and inflammation. This can lead to scarring and liver failure. The purpose of this study is to evaluate how an investigational medication affects liver scarring in people with NASH.

Participants will be given either a placebo or the investigational medication through a shot under the skin every four weeks for 13 doses. The study will also look at how the medication works in the body, any side effects, and how it affects liver health.

  • Who can participate: Adults with NASH, fibrosis stage 2 or 3, and a NAS score of 4 or higher can participate. Participants must meet specific genetic criteria and have a defined liver stiffness measurement.
  • Study details: Participants will receive either a placebo or the investigational medication by injection every four weeks. The study will observe how the medication affects liver function and any side effects.
  • Study timelines: The study will last approximately 100 weeks.
Updated on 05 Aug 2026. Study ID: GI-REGENERON-ALN-HSD, 21470
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Interested in the study?

This study is accepting only persons who receive care at a certain clinic or doctor or who are part of an invited group. Questions about this study can be directed to the study team listed in the description or contact your doctor to see if you are eligible.

Accepting Referrals by Invitation Only