Metabolic Dysfunction-Associated SteatoHepatitis (MASH)Phase 2NASHGEN-2NCT05519475
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
A Phase 2 study testing ALN-HSD in people with Metabolic Dysfunction-Associated SteatoHepatitis (MASH), run by Regeneron Pharmaceuticals at 71 sites in 4 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Metabolic Dysfunction-Associated SteatoHepatitis (MASH)
- What is being tested?
- ALN-HSD
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 71 sitesin 4 countries
- Study dates
- 9 Feb 2023to 7 Dec 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
71 sites in 4 countries. Contact the study team or a site near you to ask about taking part.
71 sites in 4 countries
United States61 sites, 35 recruiting
- Recruiting
University of Colorado Anschutz Medical Campus
Aurora, Colorado, 80045
- Terminated
Austin Clinical Research, LLC
Austin, Texas, 78745
- Recruiting
American Research Corporation
Austin, Texas, 78757
- Recruiting
Pinnacle Clinical Research - Austin
Austin, Texas, 78757
- Terminated
Mercy Medical Center
Baltimore, Maryland, 21202
- Terminated
Synergy Healthcare LLC
Bradenton, Florida, 34209
- Terminated
South Texas Research Institute (STRI) - Brownsville
Brownsville, Texas, 78520
- Terminated
San Fernando Valley Health Institute
Canoga Park, California, 91304
- Terminated
Velocity Clinical Research - Austin
Cedar Park, Texas, 78613
- Recruiting
University of Virginia Medical Center
Charlottesville, Virginia, 22903
- Terminated
Velocity Clinical Research
Chula Vista, California, 91911
- Recruiting
Southern California Research Center
Coronado, California, 92118
- Recruiting
Methodist Dallas Medical Center
Dallas, Texas, 75203
- Recruiting
Geisinger Medical Center
Danville, Pennsylvania, 17822
- Terminated
South Texas Research Institute (STRI) - Edinburg
Edinburg, Texas, 78539
- Terminated
The Institute for Liver Health II LLC DBA Arizona Clinical Trials - Flagstaff
Flagstaff, Arizona, 86001
- Recruiting
GI Associates
Flowood, Mississippi, 39232
- Recruiting
GI Alliance Research
Fort Worth, Texas, 76104
- Terminated
Allure Health at Mt. Olympus Medical Research
Friendswood, Texas, 77546
- Terminated
Velocity Clinical Research
Gardena, California, 90247
- Recruiting
Advanced Medical Trials
Georgetown, Texas, 78628
- Recruiting
Penn State Health Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
- Recruiting
Evolution Clinical Trials
Hialeah Gardens, Florida, 33016
- Recruiting
Pioneer Research Solutions, Inc.
Houston, Texas, 77099
- Terminated
Velocity Clinical Research - Huntington Park
Huntington Park, California, 90255
- Recruiting
Indiana University School of Medicine
Indianapolis, Indiana, 46202
- Recruiting
Health Awareness, inc.
Jupiter, Florida, 33458
- Terminated
R & H Clinical Research, Inc.
Katy, Texas, 77494
- Recruiting
Om Research Llc
Lancaster, California, 93534
- Terminated
Ark Clinical Research - Long Beach
Long Beach, California, 90815
- Terminated
Ark Clinical Research, LLC
Long Beach, California, 90815
- Terminated
Velocity Clinical Research - Westlake
Los Angeles, California, 90057
- Recruiting
Tandem Clinical Research
Metairie, Louisiana, 70006
- Terminated
Miami Clinical Research
Miami, Florida, 33155
- Terminated
International Medical Investigational Centers (IMIC) Incorporated
Miami, Florida, 33157
- Recruiting
Genoma Research Group, Inc.
Miami, Florida, 33173
- Terminated
US Associates in Research, LLC
Miami, Florida, 33175
- Recruiting
Med Research of Florida, LLC
Miami, Florida, 33186
- Terminated
Intermountain Health
Murray, Utah, 84107
- Recruiting
Columbia University Irving Medical Center
New York, New York, 10032
- Terminated
Deaconess Clinic - GI Specialty Center
Newburgh, Indiana, 47630
- Recruiting
Clinnova Research Solutions
Orange, California, 92868
- Recruiting
Knowledge Research Center, St. Joseph's Medical Tower
Orange, California, 92868
- Recruiting
Charter Research LLC - Orlando
Orlando, Florida, 32803
- Terminated
National Research Institute
Panorama City, California, 91402
- Recruiting
California Liver Research Institute
Pasadena, California, 91105
- Recruiting
The Institute for Liver Health II LLC DBA Arizona Liver Health - Peoria
Peoria, Arizona, 85381
- Terminated
Great Lakes Research Institute
Pharr, Texas, 78577
- Recruiting
University of Pennsylvania - Perelman Center for Advanced Medicine
Philadelphia, Pennsylvania, 19104
- Terminated
Cadena Care Inst.
Poway, California, 92064
- Recruiting
Inland Empire Clinical Trials
Rialto, California, 92377
- Recruiting
Richmond Veterans Administration Medical Center
Richmond, Virginia, 23249
- Recruiting
American Research Corporation at The Texas Liver Institute
San Antonio, Texas, 78215
- Recruiting
Pinnacle Clinical Research - San Antonio
San Antonio, Texas, 78229
- Terminated
Precision Research Institute - San Diego
San Diego, California, 92114
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
- Terminated
R & H Clinical Research
Stafford, Texas, 77477
- Recruiting
Adobe Clinical Research
Tucson, Arizona, 85712
- Recruiting
Arizona Liver Health - Tucson
Tucson, Arizona, 85712
- Recruiting
The Institute for Liver Health II LLC dba Arizona Liver Health
Tucson, Arizona, 85712
- Recruiting
Del Sol Research Management, LLC
Tucson, Arizona, 85715
South Korea5 sites
- Terminated
Pusan National University Hospital
Busan, 49241
- Terminated
Kyungpook National University Hospital
Daegu, 41944
- Terminated
Keimyung University Dongsan Hospital
Daegu, 42601
- Terminated
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, 13620
- Terminated
Hanyang University Seoul Hospital
Seoul, 04763
Puerto Rico4 sites, 1 recruiting
- Terminated
Isis Clinical Research Center
Guaynabo, San Juan, 00969
- Terminated
Klinical Investigations
San Juan, 00909
- Terminated
Latin Clinical Trial Center
San Juan, 00909
- Recruiting
Fundacion de Investigacion (FDI) Clinical Research
San Juan, 00927
About this study
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
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
- Being tested
- ALN-HSD, Placebo
- Keywords
- Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD), Histologically confirmed MASH, Genetic risk alleles for MASH at the HSD17B13 locus, Non-Alcoholic SteatoHepatitis (NASH)
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALN-HSDDrug
Administered per the protocol
PlaceboDrug
Administered per the protocol
| Study group | Role | What they receive |
|---|---|---|
| ALN-HSD | Experimental | Randomized 1:1 Receives: Drug: ALN-HSD |
| Placebo | Placebo comparator | Randomized 1:1 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in quantitative liver Fibrosis (qFibrosis)
Change in the continuous qFibrosis score measured by second harmonic generation/two-photon excitation microscopy
Measured: 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
Measured: Baseline to week 52
Resolution of MASH with no worsening of NASH-CRN fibrosis on liver biopsy
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
Measured: Baseline to week 52
Change in serum ALanine aminoTransferase (ALT)
Measured: Baseline to week 52
Change in serum ASpartate aminoTransferase (AST)
Measured: Baseline to week 52
Change in Enhanced Liver Fibrosis (ELF)
Measured: Baseline to week 52
Change in N-terminal type III Collagen PROropeptide (PRO-C3)
Measured: Baseline to week 52
Change in NIS4, a non-invasive fibrosis biomarker of NASH
Measured: Baseline to week 52
Change in Fibrosis-4 (FIB-4)
Measured: Baseline to week 52
Change in hepatic HydroxySteroiD 17β dehydrogenase 13 (HSD17B13) transcript level
Measured: Baseline to week 52
Incidence of progression in qFibrosis on liver biopsy
Measured: Baseline to week 52
Occurrence of Treatment-Emergent Adverse Events (TEAEs)
Measured: Baseline to week 84
Severity of TEAEs
Measured: Baseline to week 84
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2022
- Study start9 Feb 2023
- Primary completion27 Apr 2028 (estimated)
- Study completion7 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metabolic Dysfunction-Associated SteatoHepatitis (MASH)Studies of the same condition, open and under way.
- More trials run by Regeneron PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Regeneron Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trial Management, Study director, Regeneron Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05519475
- Sponsor's protocol ID
- ALN-HSD-NASH-2130
- Acronym
- NASHGEN-2
- Status last verified
- Oct 2026
- First submitted
- 15 Aug 2022
- Last updated
- 8 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05519475
- Acronym / sponsor ID
- NASHGEN-2 / ALN-HSD-NASH-2130
- Keywords
- Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD), Histologically confirmed MASH, Genetic risk alleles for MASH at the HSD17B13 locus, Non-Alcoholic SteatoHepatitis (NASH)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Regeneron PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 9 Feb 2023 (actual)
- Primary completion
- 27 Apr 2028 (estimated)
- Study completion
- 7 Dec 2028 (estimated)
- First posted
- 29 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ALN-HSD | Experimental | Drug: ALN-HSDRandomized 1:1 |
| Placebo | Placebo comparator | Drug: PlaceboRandomized 1:1 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ALN-HSDAdministered per the protocol | Drug | ALN-HSD |
| PlaceboAdministered per the protocol | Drug | Placebo |
Primary outcome
Change in quantitative liver Fibrosis (qFibrosis)
Time frame: Baseline to week 52
Change in the continuous qFibrosis score measured by second harmonic generation/two-photon excitation microscopy
12 secondary outcomes
Improvement of Non-Alcoholic Steatohepatitis Clinical Research Network (NASH-CRN) Fibrosis (F) stage by ≥1 stage without worsening of MASH on liver biopsy
Time frame: Baseline to week 52
Resolution of MASH with no worsening of NASH-CRN fibrosis on liver biopsy
Time frame: Baseline to week 52
Change in serum ALanine aminoTransferase (ALT)
Time frame: Baseline to week 52
Change in serum ASpartate aminoTransferase (AST)
Time frame: Baseline to week 52
Change in Enhanced Liver Fibrosis (ELF)
Time frame: Baseline to week 52
Change in N-terminal type III Collagen PROropeptide (PRO-C3)
Time frame: Baseline to week 52
Change in NIS4, a non-invasive fibrosis biomarker of NASH
Time frame: Baseline to week 52
Change in Fibrosis-4 (FIB-4)
Time frame: Baseline to week 52
Change in hepatic HydroxySteroiD 17β dehydrogenase 13 (HSD17B13) transcript level
Time frame: Baseline to week 52
Incidence of progression in qFibrosis on liver biopsy
Time frame: Baseline to week 52
Occurrence of Treatment-Emergent Adverse Events (TEAEs)
Time frame: Baseline to week 84
Severity of TEAEs
Time frame: Baseline to week 84
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2026.
- Study Informational WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
Related trials for Metabolic Dysfunction-Associated SteatoHepatitis (MASH)
RecruitingPhase 3
A Study Evaluating Efruxifermin in Subjects With Non-Cirrhotic Nonalcoholic Steatohepatitis (NASH)/Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Fibrosis
NASH With Fibrosis, MASH With Fibrosis
RecruitingPhase 1
A Study of INI-822 in Healthy Volunteers and Participants With Metabolic Dysfunction-Associated Steatohepatitis (MASH) or Presumed MASH
Metabolic Dysfunction-Associated Steatohepatitis
RecruitingPhase 3
Trial to Evaluate ALN-CIDEB in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
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RecruitingPhase 3
A Pivotal Clinical Study to Investigate the Safety and Efficacy of Efimosfermin Compared With Placebo in Adult Participants With Compensated Cirrhosis Due to Metabolic Dysfunction-associated Steatohepatitis (MASH)
Metabolic Dysfunction-associated Steatohepatitis
RecruitingPhase 3
A Study to Investigate Safety and Efficacy of Efimosfermin Compared With Placebo in Adult Participants With Compensated Cirrhosis Due to Metabolic Dysfunction-associated Steatohepatitis (MASH)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Clinical Trial Management study director
Regeneron Pharmaceuticals
71 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ALN-HSD in people with Metabolic Dysfunction-Associated SteatoHepatitis (MASH), run by Regeneron Pharmaceuticals at 71 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 71 sites in United States, South Korea, Puerto Rico, Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Clinical Trials Administrator (844-734-6643, clinicaltrials@regeneron.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in quantitative liver Fibrosis (qFibrosis) (time frame: Baseline to week 52). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2026.