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
- Conditions
- Metabolic Dysfunction-associated Steatohepatitis (MASH)
- Interventions
- Drug: Placebo
- 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
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 90
- 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-Clinical Research Network (CRN)
- NAS score ≥3, as defined in the protocol
- Meets genotype criteria for study enrollment, as defined in the protocol
- Has protocol defined FibroScan®-AST (FAST) score at screening or within approximately 12 weeks of screening
Key
- 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
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 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 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
Trial Locations
- Locations (65)
GI Associates
🇺🇸Flowood, Mississippi, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
JCHO Hokkaido Hospital
🇯🇵Sapporo, Hokkaido, Japan
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
Velocity Clinical Research - Huntington Park
🇺🇸Huntington Park, California, United States
Ark Clinical Research - Long Beach
🇺🇸Long Beach, California, United States
Velocity Clinical Research - Westlake
🇺🇸Los Angeles, California, United States
Clinnova Research Solutions
🇺🇸Orange, California, United States
National Research Institute
🇺🇸Panorama City, California, United States
California Liver Research Institute
🇺🇸Pasadena, California, United States
Cadena Care Inst.
🇺🇸Poway, California, United States
Inland Empire Liver Foundation
🇺🇸Rialto, California, United States
Precision Research Institute - San Diego
🇺🇸San Diego, California, United States
University of Colorado Anschutz Medical Campus
🇺🇸Aurora, Colorado, United States
Synergy Healthcare, LLC
🇺🇸Bradenton, Florida, United States
Evolution Clinical Trials
🇺🇸Hialeah Gardens, Florida, United States
Miami Clinical Research Center
🇺🇸Miami, Florida, United States
IMIC, Inc
🇺🇸Miami, Florida, United States
Genoma Research Group, Inc.
🇺🇸Miami, Florida, United States
US Associates in Research, LLC
🇺🇸Miami, Florida, United States
Med Research of Florida, LLC
🇺🇸Miami, Florida, United States
Indiana University School of Medicine
🇺🇸Indianapolis, Indiana, United States
Deaconess Clinic - GI Specialty Center
🇺🇸Newburgh, Indiana, United States
Tandem Clinical Research
🇺🇸Metairie, Louisiana, United States
Mercy Medical Center
🇺🇸Baltimore, Maryland, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Columbia University Irving Medical Center
🇺🇸New York, New York, United States
Penn State Health Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
University of Pennsylvania - Perelman Center for Advanced Medicine
🇺🇸Philadelphia, Pennsylvania, United States
IMA Clinical Research Austin
🇺🇸Austin, Texas, United States
American Research Corporation
🇺🇸Austin, Texas, United States
Pinnacle Clinical Research - Austin
🇺🇸Austin, Texas, United States
South Texas Research Institute (STRI) - Brownsville
🇺🇸Brownsville, Texas, United States
Velocity Clinical Research - Austin
🇺🇸Cedar Park, Texas, United States
Methodist Dallas Medical Center
🇺🇸Dallas, Texas, United States
South Texas Research Institute (STRI) - Edinburg
🇺🇸Edinburg, Texas, United States
GI Alliance Research
🇺🇸Fort Worth, Texas, United States
Allure Health at Mt. Olympus Medical Research
🇺🇸Friendswood, Texas, United States
Advanced Medical Trials
🇺🇸Georgetown, Texas, United States
Pioneer Research Solutions, Inc.
🇺🇸Houston, Texas, United States
R & H Clinical Research, Inc.
🇺🇸Katy, Texas, United States
Great Lakes Research Institute
🇺🇸Pharr, Texas, United States
American Research Corporation at The Texas Liver Institute
🇺🇸San Antonio, Texas, United States
Pinnacle Clinical Research - San Antonio
🇺🇸San Antonio, Texas, United States
R & H Clinical Research
🇺🇸Stafford, Texas, United States
University of Virginia Medical Center
🇺🇸Charlottesville, Virginia, United States
Richmond Va Medical Center
🇺🇸Richmond, Virginia, United States
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Kyungpook National University Hospital
🇰🇷Daegu, Korea, Republic of
Keimyung University Dongsan Hospital
🇰🇷Daegu, Korea, Republic of
Hanyang University Seoul Hospital
🇰🇷Seoul, Korea, Republic of
Isis Clinical Research Center
🇵🇷Guaynabo, Puerto Rico
Klinical Investigations
🇵🇷San Juan, Puerto Rico
Latin Clinical Trial Center
🇵🇷San Juan, Puerto Rico
Fundacion de Investigacion (FDI) Clinical Research
🇵🇷San Juan, Puerto Rico