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

Phase 2

Recruiting

• Conditions: Metabolic Dysfunction-associated Steatohepatitis (MASH)
• Interventions: Drug: Placebo; Drug: ALN-HSD

• Registration Number: NCT05519475
• Lead Sponsor: Regeneron Pharmaceuticals

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-08-15
• Study First Submitted QC: 2022-08-26
• Study First Posted: 2022-08-29
• Study Start: 2023-02-09
• Status Verified: 2025-08
• Last Update Submitted: 2025-09-03
• Last Update Posted: 2025-09-05
• Primary Completion: 2027-09-08
• Study Completion: 2027-09-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 90

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-Clinical Research Network (CRN)
3. NAS score ≥3, as defined in the protocol
4. Meets genotype criteria for study enrollment, as defined in the protocol
5. Has 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Randomized 1:1
ALN-HSD	ALN-HSD	Randomized 1:1

Primary Outcome Measures

Name	Time	Method
Change in qFibrosis	Baseline to week 52	Change in the continuous quantitative liver fibrosis (qFibrosis) score measured by second harmonic generation/two-photon excitation microscopy

Secondary Outcome Measures

Name	Time	Method
Change in hepatic hydroxysteroid 17β dehydrogenase 13 (HSD17B13) transcript level	Baseline to week 52
Incidence of progression in qFibrosis on liver biopsy	Baseline to week 52
Incidence of treatment-emergent adverse events (TEAEs)	Baseline to week 84
Severity of treatment-emergent adverse events (TEAEs)	Baseline to week 84
Improvement of non-alcoholic steatohepatitis clinical research network (NASH-CRN) fibrosis (F) stage by ≥1 stage without worsening of MASH on liver biopsy	Baseline to week 52
Resolution of MASH with no worsening of NASH-CRN fibrosis on liver biopsy	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
Change in serum alanine aminotransferase (ALT)	Baseline to week 52
Change in serum aspartate aminotransferase (AST)	Baseline to week 52
Change in enhanced liver fibrosis (ELF)	Baseline to week 52
Change in N-terminal type III collagen propeptide (PRO-C3)	Baseline to week 52
Change in NIS4, a non-invasive fibrosis biomarker of NASH	Baseline to week 52
Change in Fibrosis-4 (FIB-4)	Baseline to week 52

Trial Locations

Locations (70)

Arizona Liver Health; 🇺🇸 Chandler, Arizona, United States

The Institute for Liver Health II LLC DBA Arizona Clinical Trials - Flagstaff; 🇺🇸 Flagstaff, Arizona, United States

The Institute for Liver Health II LLC DBA Arizona Liver Health - Peoria; 🇺🇸 Peoria, Arizona, United States

Adobe Clinical Research; 🇺🇸 Tucson, Arizona, United States

Arizona Liver Health - Tucson; 🇺🇸 Tucson, Arizona, United States

Del Sol Research Management, LLC; 🇺🇸 Tucson, Arizona, United States

San Fernando Valley Health Institute; 🇺🇸 Canoga Park, California, United States

Velocity Clinical Research; 🇺🇸 Gardena, California, United States

Southern California Research Center; 🇺🇸 Coronado, California, United States

Ark Clinical Research - Fountain Valley; 🇺🇸 Fountain Valley, California, United States

Scroll for more (60 remaining)