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NCT05519475PHASE2Recruiting

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

Regeneron Pharmaceuticals

Start Date

2/9/2023

Completion Date

12/7/2028

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

Eligibility Criteria

Age Range: 18 years to 75 years

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

Interventions

DRUG

ALN-HSD

DRUG

Placebo

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Conditions

Metabolic Dysfunction-Associated SteatoHepatitis (MASH)

Locations

Arizona Liver Health

Chandler, Arizona 85224

United States

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

Flagstaff, Arizona 86001

United States

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

Peoria, Arizona 85381

United States

Adobe Clinical Research

Tucson, Arizona 85712

United States

Arizona Liver Health - Tucson

Tucson, Arizona 85712

United States

Del Sol Research Management, LLC

Tucson, Arizona 85715

United States

San Fernando Valley Health Institute

Canoga Park, California 91304

United States

Velocity Clinical Research

Chula Vista, California 91911

United States

Southern California Research Center

Coronado, California 92118

United States

Ark Clinical Research - Fountain Valley

Fountain Valley, California 92708

United States

Velocity Clinical Research

Gardena, California 90247

United States

Velocity Clinical Research - Huntington Park

Huntington Park, California 90255

United States

Om Research Llc

Lancaster, California 93534

United States

Ark Clinical Research - Long Beach

Long Beach, California 90815

United States

Velocity Clinical Research - Westlake

Los Angeles, California 90057

United States

Clinnova Research Solutions

Orange, California 92868

United States

Knowledge Research Center, St. Joseph's Medical Tower

Orange, California 92868

United States

National Research Institute

Panorama City, California 91402

United States

California Liver Research Institute

Pasadena, California 91105

United States

Cadena Care Inst.

Poway, California 92064

United States

Inland Empire Liver Foundation

Rialto, California 92377

United States

Precision Research Institute - San Diego

San Diego, California 92114

United States

University of Colorado Anschutz Medical Campus

Aurora, Colorado 80045

United States

Synergy Healthcare LLC

Bradenton, Florida 34209

United States

Evolution Clinical Trials

Hialeah Gardens, Florida 33016

United States

Health Awareness, inc.

Jupiter, Florida 33458

United States

Miami Clinical Research

Miami, Florida 33155

United States

International Medical Investigational Centers (IMIC) Incorporated

Miami, Florida 33157

United States

Genoma Research Group, Inc.

Miami, Florida 33173

United States

US Associates in Research, LLC

Miami, Florida 33175

United States

Med Research of Florida, LLC

Miami, Florida 33186

United States

Charter Research LLC - Orlando

Orlando, Florida 32803

United States

Indiana University School of Medicine

Indianapolis, Indiana 46202

United States

Deaconess Clinic - GI Specialty Center

Newburgh, Indiana 47630

United States

Tandem Clinical Research

Metairie, Louisiana 70006

United States

Mercy Medical Center

Baltimore, Maryland 21202

United States

GI Associates

Flowood, Mississippi 39232

United States

Washington University School of Medicine

St Louis, Missouri 63110

United States

Columbia University Irving Medical Center

New York, New York 10032

United States

Geisinger Medical Center

Danville, Pennsylvania 17822

United States

Penn State Health Milton S. Hershey Medical Center

Hershey, Pennsylvania 17033

United States

University of Pennsylvania - Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania 19104

United States

Austin Clinical Research, LLC

Austin, Texas 78745

United States

American Research Corporation

Austin, Texas 78757

United States

Pinnacle Clinical Research - Austin

Austin, Texas 78757

United States

South Texas Research Institute (STRI) - Brownsville

Brownsville, Texas 78520

United States

Velocity Clinical Research - Austin

Cedar Park, Texas 78613

United States

Methodist Dallas Medical Center

Dallas, Texas 75203

United States

South Texas Research Institute (STRI) - Edinburg

Edinburg, Texas 78539

United States

GI Alliance Research

Fort Worth, Texas 76104

United States

Allure Health at Mt. Olympus Medical Research

Friendswood, Texas 77546

United States

Advanced Medical Trials

Georgetown, Texas 78628

United States

Pioneer Research Solutions, Inc.

Houston, Texas 77099

United States

R & H Clinical Research, Inc.

Katy, Texas 77494

United States

Great Lakes Research Institute

Pharr, Texas 78577

United States

American Research Corporation at The Texas Liver Institute

San Antonio, Texas 78215

United States

Pinnacle Clinical Research - San Antonio

San Antonio, Texas 78229

United States

R & H Clinical Research

Stafford, Texas 77477

United States

Intermountain Health

Murray, Utah 84107

United States

University of Virginia Medical Center

Charlottesville, Virginia 22903

United States

Richmond Veterans Administration Medical Center

Richmond, Virginia 23249

United States

JCHO Hokkaido Hospital

Sapporo, Hokkaido 062-8618

Japan

Isis Clinical Research Center

Guaynabo, San Juan 00969

Puerto Rico

Klinical Investigations

San Juan, 00909

Puerto Rico

Latin Clinical Trial Center

San Juan, 00909

Puerto Rico

Fundacion de Investigacion (FDI) Clinical Research

San Juan, 00927

Puerto Rico

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do 13620

South Korea

Pusan National University Hospital

Busan, 49241

South Korea

Kyungpook National University Hospital

Daegu, 41944

South Korea

Keimyung University Dongsan Hospital

Daegu, 42601

South Korea

Hanyang University Seoul Hospital

Seoul, 04763

South Korea