Metabolic Dysfunction-Associated SteatoHepatitis (MASH)
Conditions
Keywords
Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD), Histologically confirmed MASH, Genetic risk alleles for MASH at the HSD17B13 locus, Non-Alcoholic SteatoHepatitis (NASH)
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
Interventions
DRUGALN-HSD
Administered per the protocol
DRUGPlacebo
Administered per the protocol
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion 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-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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in quantitative liver Fibrosis (qFibrosis) | Baseline to week 52 | Change in the continuous qFibrosis score measured by second harmonic generation/two-photon excitation microscopy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 PROropeptide (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 | — |
| Occurrence of Treatment-Emergent Adverse Events (TEAEs) | Baseline to week 84 | — |
| Severity of TEAEs | Baseline to week 84 | — |
Countries
Japan, Puerto Rico, South Korea, United States
Contacts
CONTACTClinical Trials Administrator
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed