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NCT Number: NCT05519475

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

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

Recruiting

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Key information

Conditions

Metabolic Dysfunction-Associated Steatohepatitis (MASH) Digestive System Diseases Fatty Liver Liver Diseases Non-alcoholic Fatty Liver Disease

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

JCHO Hokkaido Hospital, Sapporo, Hokkaido, Japan

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key 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

Key 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

Treatment and study plan

ALN-HSD

Drug

Administered per the protocol

Placebo

Drug

Administered per the protocol

Primary outcomes

  1. Change in quantitative liver Fibrosis (qFibrosis)

    Time frame: Baseline to week 52

    Change in the continuous qFibrosis score measured by second harmonic generation/two-photon excitation microscopy

Secondary outcomes

  1. 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

  2. Resolution of MASH with no worsening of NASH-CRN fibrosis on liver biopsy

    Time frame: Baseline to week 52

    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

  3. Change in serum ALanine aminoTransferase (ALT)

    Time frame: Baseline to week 52

  4. Change in serum ASpartate aminoTransferase (AST)

    Time frame: Baseline to week 52

  5. Change in Enhanced Liver Fibrosis (ELF)

    Time frame: Baseline to week 52

  6. Change in N-terminal type III Collagen PROropeptide (PRO-C3)

    Time frame: Baseline to week 52

  7. Change in NIS4, a non-invasive fibrosis biomarker of NASH

    Time frame: Baseline to week 52

  8. Change in Fibrosis-4 (FIB-4)

    Time frame: Baseline to week 52

  9. Change in hepatic HydroxySteroiD 17β dehydrogenase 13 (HSD17B13) transcript level

    Time frame: Baseline to week 52

  10. Incidence of progression in qFibrosis on liver biopsy

    Time frame: Baseline to week 52

  11. Occurrence of Treatment-Emergent Adverse Events (TEAEs)

    Time frame: Baseline to week 84

  12. Severity of TEAEs

    Time frame: Baseline to week 84

Study contacts

Contact information is provided by the study sponsor or research team.

Clinical Trials Administrator

CONTACT

[email protected]

844-734-6643

Sponsors and collaborators

Lead sponsor

Regeneron Pharmaceuticals

Industry

Registry information

Official study 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

Acronym: NASHGEN-2

Important dates

Study start
2023
Primary completion
2028
Study completion
2028
First posted
Aug 29, 2022
Registry last updated
Jul 8, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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