Home › Trials › NCT05519475

Gene silencing treatment for chronic liver disease in genetically at-risk adults

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

PHASE2 · Regeneron Pharmaceuticals · NCT05519475

This study is testing a new drug to see if it can help adults at higher genetic risk for liver disease by reducing liver damage and inflammation.

Quick facts

PhasePHASE2
Study typeInterventional
Enrollment120 (estimated)
Ages18 Years to 75 Years
SexAll
SponsorRegeneron Pharmaceuticals (industry)
Locations71 sites (Chandler, Arizona and 70 other locations)
Trial IDNCT05519475 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the investigational drug ALN-HSD for treating metabolic dysfunction-associated steatohepatitis (MASH) in adults with increased genetic risk. The study aims to evaluate the drug's effectiveness in reducing liver scarring and inflammation associated with MASH. Participants will be monitored for liver function improvements, potential side effects, and the pharmacokinetics of the drug. The trial includes a placebo group for comparison.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older diagnosed with MASH and fibrosis stages 2 or 3.

Not a fit: Patients with other chronic liver diseases or a history of substance abuse may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve liver health and reduce the risk of severe liver complications in patients with MASH.

How similar studies have performed: While gene silencing approaches are emerging, this specific application for MASH is novel and has not been extensively tested in prior studies.

Eligibility criteria

Show full inclusion / exclusion criteria 
Key Inclusion Criteria:

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

Key Exclusion Criteria:

1. Evidence of other forms of known chronic liver disease, as defined in the protocol
2. Known history of alcohol or other substance abuse within the last year or at any time during screening, as defined in the protocol
3. History of Type 1 diabetes
4. Bariatric surgery within approximately 5 years prior to or planned during the study period
5. 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

Where this trial is running

Chandler, Arizona and 70 other locations

+21 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Metabolic Dysfunction-Associated SteatoHepatitis, Metabolic dysfunction-Associated Steatotic Liver Disease, Histologically confirmed MASH, Genetic risk alleles for MASH at the HSD17B13 locus, Non-Alcoholic SteatoHepatitis

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.