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

NCT05519475 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: ALN-HSD-NASH-2130
• Study Type: interventional
• Target: 120
• Locations: 4 countries
• Sites: 71

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 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

Conditions

Metabolic Dysfunction-Associated SteatoHepatitis (MASH)

Keywords

Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD); Histologically confirmed MASH; Genetic risk alleles for MASH at the HSD17B13 locus; Non-Alcoholic SteatoHepatitis (NASH)

Outcome Measures

Primary Outcomes (1)

• Change in quantitative liver Fibrosis (qFibrosis)

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

  Baseline to week 52

Secondary Outcomes (12)

• 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

• 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

Study Arms (2)

ALN-HSD

EXPERIMENTAL

Randomized 1:1

Drug: ALN-HSD

Placebo

PLACEBO COMPARATOR

Randomized 1:1

Drug: Placebo

Interventions

ALN-HSD DRUG

Administered per the protocol

ALN-HSD

Placebo DRUG

Administered per the protocol

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (71)

Arizona Liver Health

Chandler, Arizona, 85224, United States

RECRUITING

The Institute for Liver Health II LLC DBA Arizona Clinical Trials - Flagstaff

Flagstaff, Arizona, 86001, United States

TERMINATED

The Institute for Liver Health II LLC DBA Arizona Liver Health - Peoria

Peoria, Arizona, 85381, United States

RECRUITING

Adobe Clinical Research

Tucson, Arizona, 85712, United States

RECRUITING

Arizona Liver Health - Tucson

Tucson, Arizona, 85712, United States

RECRUITING

Del Sol Research Management, LLC

Tucson, Arizona, 85715, United States

RECRUITING

San Fernando Valley Health Institute

Canoga Park, California, 91304, United States

TERMINATED

Velocity Clinical Research

Chula Vista, California, 91911, United States

TERMINATED

Southern California Research Center

Coronado, California, 92118, United States

RECRUITING

Ark Clinical Research - Fountain Valley

Fountain Valley, California, 92708, United States

RECRUITING

Velocity Clinical Research

Gardena, California, 90247, United States

TERMINATED

Velocity Clinical Research - Huntington Park

Huntington Park, California, 90255, United States

TERMINATED

Om Research Llc

Lancaster, California, 93534, United States

RECRUITING

Ark Clinical Research - Long Beach

Long Beach, California, 90815, United States

RECRUITING

Velocity Clinical Research - Westlake

Los Angeles, California, 90057, United States

TERMINATED

Clinnova Research Solutions

Orange, California, 92868, United States

RECRUITING

Knowledge Research Center, St. Joseph's Medical Tower

Orange, California, 92868, United States

RECRUITING

National Research Institute

Panorama City, California, 91402, United States

TERMINATED

California Liver Research Institute

Pasadena, California, 91105, United States

RECRUITING

Cadena Care Inst.

Poway, California, 92064, United States

TERMINATED

Inland Empire Liver Foundation

Rialto, California, 92377, United States

RECRUITING

Precision Research Institute - San Diego

San Diego, California, 92114, United States

TERMINATED

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

RECRUITING

Synergy Healthcare LLC

Bradenton, Florida, 34209, United States

TERMINATED

Evolution Clinical Trials

Hialeah Gardens, Florida, 33016, United States

RECRUITING

Health Awareness, inc.

Jupiter, Florida, 33458, United States

RECRUITING

Miami Clinical Research

Miami, Florida, 33155, United States

TERMINATED

International Medical Investigational Centers (IMIC) Incorporated

Miami, Florida, 33157, United States

TERMINATED

Genoma Research Group, Inc.

Miami, Florida, 33173, United States

RECRUITING

US Associates in Research, LLC

Miami, Florida, 33175, United States

TERMINATED

Med Research of Florida, LLC

Miami, Florida, 33186, United States

RECRUITING

Charter Research LLC - Orlando

Orlando, Florida, 32803, United States

RECRUITING

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

RECRUITING

Deaconess Clinic - GI Specialty Center

Newburgh, Indiana, 47630, United States

RECRUITING

Tandem Clinical Research

Metairie, Louisiana, 70006, United States

RECRUITING

Mercy Medical Center

Baltimore, Maryland, 21202, United States

TERMINATED

GI Associates

Flowood, Mississippi, 39232, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

Geisinger Medical Center

Danville, Pennsylvania, 17822, United States

RECRUITING

Penn State Health Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

RECRUITING

University of Pennsylvania - Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Austin Clinical Research, LLC

Austin, Texas, 78745, United States

TERMINATED

American Research Corporation

Austin, Texas, 78757, United States

RECRUITING

Pinnacle Clinical Research - Austin

Austin, Texas, 78757, United States

RECRUITING

South Texas Research Institute (STRI) - Brownsville

Brownsville, Texas, 78520, United States

RECRUITING

Velocity Clinical Research - Austin

Cedar Park, Texas, 78613, United States

TERMINATED

Methodist Dallas Medical Center

Dallas, Texas, 75203, United States

RECRUITING

South Texas Research Institute (STRI) - Edinburg

Edinburg, Texas, 78539, United States

TERMINATED

GI Alliance Research

Fort Worth, Texas, 76104, United States

RECRUITING

Allure Health at Mt. Olympus Medical Research

Friendswood, Texas, 77546, United States

TERMINATED

Advanced Medical Trials

Georgetown, Texas, 78628, United States

RECRUITING

Pioneer Research Solutions, Inc.

Houston, Texas, 77099, United States

RECRUITING

R & H Clinical Research, Inc.

Katy, Texas, 77494, United States

TERMINATED

Great Lakes Research Institute

Pharr, Texas, 78577, United States

TERMINATED

American Research Corporation at The Texas Liver Institute

San Antonio, Texas, 78215, United States

RECRUITING

Pinnacle Clinical Research - San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

R & H Clinical Research

Stafford, Texas, 77477, United States

TERMINATED

Intermountain Health

Murray, Utah, 84107, United States

RECRUITING

University of Virginia Medical Center

Charlottesville, Virginia, 22903, United States

RECRUITING

Richmond Veterans Administration Medical Center

Richmond, Virginia, 23249, United States

RECRUITING

JCHO Hokkaido Hospital

Sapporo, Hokkaido, 062-8618, Japan

TERMINATED

Isis Clinical Research Center

Guaynabo, San Juan, 00969, Puerto Rico

TERMINATED

Klinical Investigations

San Juan, 00909, Puerto Rico

TERMINATED

Latin Clinical Trial Center

San Juan, 00909, Puerto Rico

TERMINATED

Fundacion de Investigacion (FDI) Clinical Research

San Juan, 00927, Puerto Rico

RECRUITING

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

TERMINATED

Pusan National University Hospital

Busan, 49241, South Korea

TERMINATED

Kyungpook National University Hospital

Daegu, 41944, South Korea

TERMINATED

Keimyung University Dongsan Hospital

Daegu, 42601, South Korea

TERMINATED

Hanyang University Seoul Hospital

Seoul, 04763, South Korea

TERMINATED

Related Links

• Study Informational Website

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Clinical Trials Administrator

CONTACT

844-734-6643; clinicaltrials@regeneron.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2022
• First Posted: August 29, 2022
• Study Start: February 9, 2023
• Primary Completion (Estimated): April 27, 2028
• Study Completion (Estimated): December 7, 2028
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: When Regeneron has: * received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development * made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry) * has the legal authority to share the data, and * ensured the ability to protect participant privacy
• Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf

Locations

KR (5); US (61); JP (1); PR (4)