Clinical trial 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
Official 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
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)
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2022-08-29
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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-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

Primary outcomes:
measure: Change in qFibrosis
timeFrame: Baseline to week 52
Secondary outcomes:
measure: Improvement of non-alcoholic steatohepatitis clinical research network (NASH-CRN) fibrosis (F) stage by ≥1 stage without worsening of MASH on liver biopsy
timeFrame: Baseline to week 52
measure: Resolution of MASH with no worsening of NASH-CRN fibrosis on liver biopsy
timeFrame: Baseline to week 52
measure: Change in serum alanine aminotransferase (ALT)
timeFrame: Baseline to week 52
measure: Change in serum aspartate aminotransferase (AST)
timeFrame: Baseline to week 52
measure: Change in enhanced liver fibrosis (ELF)
timeFrame: Baseline to week 52
measure: Change in N-terminal type III collagen propeptide (PRO-C3)
timeFrame: Baseline to week 52
measure: Change in NIS4, a non-invasive fibrosis biomarker of NASH
timeFrame: Baseline to week 52
measure: Change in Fibrosis-4 (FIB-4)
timeFrame: Baseline to week 52
measure: Change in hepatic hydroxysteroid 17β dehydrogenase 13 (HSD17B13) transcript level
timeFrame: Baseline to week 52
measure: Incidence of progression in qFibrosis on liver biopsy
timeFrame: Baseline to week 52
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Baseline to week 84
measure: Severity of treatment-emergent adverse events (TEAEs)
timeFrame: Baseline to week 84
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Arizona Liver Health
state: Arizona
city: Flagstaff
country: United States
facility: The Institute for Liver Health II LLC DBA Arizona Clinical Trials - Flagstaff
state: Arizona
city: Peoria
country: United States
facility: The Institute for Liver Health II LLC DBA Arizona Liver Health - Peoria
state: Arizona
city: Tucson
country: United States
facility: Adobe Clinical Research
state: Arizona
city: Tucson
country: United States
facility: Arizona Liver Health - Tucson
state: Arizona
city: Tucson
country: United States
facility: Del Sol Research Management, LLC
state: Arizona
city: Canoga Park
country: United States
facility: San Fernando Valley Health Institute
state: California
city: Chula Vista
country: United States
facility: Velocity Clinical Research
state: California
city: Coronado
country: United States
facility: Southern California Research Center
state: California
city: Fountain Valley
country: United States
facility: Ark Clinical Research - Fountain Valley
state: California
city: Gardena
country: United States
facility: Velocity Clinical Research
state: California
city: Huntington Park
country: United States
facility: Velocity Clinical Research - Huntington Park
state: California
city: Long Beach
country: United States
facility: Ark Clinical Research - Long Beach
state: California
city: Los Angeles
country: United States
facility: Velocity Clinical Research - Westlake
state: California
city: Orange
country: United States
facility: Clinnova Research Solutions
state: California
city: Panorama City
country: United States
facility: National Research Institute
state: California
city: Pasadena
country: United States
facility: California Liver Research Institute
state: California
city: Poway
country: United States
facility: Cadena Care Inst.
state: California
city: Rialto
country: United States
facility: Inland Empire Liver Foundation
state: California
city: San Diego
country: United States
facility: Precision Research Institute - San Diego
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Bradenton
country: United States
facility: Synergy Healthcare, LLC
state: Florida
city: Hialeah Gardens
country: United States
facility: Evolution Clinical Trials
state: Florida
city: Miami
country: United States
facility: Miami Clinical Research Center
state: Florida
city: Miami
country: United States
facility: IMIC, Inc
state: Florida
city: Miami
country: United States
facility: Genoma Research Group, Inc.
state: Florida
city: Miami
country: United States
facility: US Associates in Research, LLC
state: Florida
city: Miami
country: United States
facility: Med Research of Florida, LLC
state: Florida
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Newburgh
country: United States
facility: Deaconess Clinic - GI Specialty Center
state: Indiana
city: Metairie
country: United States
facility: Tandem Clinical Research
state: Louisiana
city: Baltimore
country: United States
facility: Mercy Medical Center
state: Maryland
city: Flowood
country: United States
facility: GI Associates
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Health Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania - Perelman Center for Advanced Medicine
state: Pennsylvania
city: Austin
country: United States
facility: IMA Clinical Research Austin
state: Texas
city: Austin
country: United States
facility: American Research Corporation
state: Texas
city: Austin
country: United States
facility: Pinnacle Clinical Research - Austin
state: Texas
city: Brownsville
country: United States
facility: South Texas Research Institute (STRI) - Brownsville
state: Texas
city: Cedar Park
country: United States
facility: Velocity Clinical Research - Austin
state: Texas
city: Dallas
country: United States
facility: Methodist Dallas Medical Center
state: Texas
city: Edinburg
country: United States
facility: South Texas Research Institute (STRI) - Edinburg
state: Texas
city: Fort Worth
country: United States
facility: GI Alliance Research
state: Texas
city: Friendswood
country: United States
facility: Allure Health at Mt. Olympus Medical Research
state: Texas
city: Georgetown
country: United States
facility: Advanced Medical Trials
state: Texas
city: Houston
country: United States
facility: Pioneer Research Solutions, Inc.
state: Texas
city: Katy
country: United States
facility: R & H Clinical Research, Inc.
state: Texas
city: Pharr
country: United States
facility: Great Lakes Research Institute
state: Texas
city: San Antonio
country: United States
facility: American Research Corporation at The Texas Liver Institute
state: Texas
city: San Antonio
country: United States
facility: Pinnacle Clinical Research - San Antonio
state: Texas
city: Stafford
country: United States
facility: R & H Clinical Research
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Medical Center
state: Virginia
city: Richmond
country: United States
facility: Richmond Va Medical Center
state: Virginia
city: Sapporo
country: Japan
facility: JCHO Hokkaido Hospital
state: Hokkaido
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Hospital
city: Seoul
country: Korea, Republic of
facility: Hanyang University Seoul Hospital
city: Guaynabo
country: Puerto Rico
facility: Isis Clinical Research Center
city: San Juan
country: Puerto Rico
facility: Klinical Investigations
city: San Juan
country: Puerto Rico
facility: Latin Clinical Trial Center
city: San Juan
country: Puerto Rico
facility: Fundacion de Investigacion (FDI) Clinical Research
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: