Metabolic Dysfunction-Associated Steatohepatitis (MASH)
Conditions
Keywords
F2 or F3 MASH, Fibrotic MASH, Nonalcoholic Fatty Liver Disease (NAFLD), Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD), Liver Inflammation, Liver Fibrosis, Cirrhosis
Brief summary
This study will test a Regeneron study drug called ALN-CIDEB to find out whether it may help treat a liver disease called MASH. In this study, researchers are looking at the effect of ALN-CIDEB on reducing liver fat, liver injury, and liver scarring. The study will compare ALN-CIDEB with placebo to understand how well ALN-CIDEB works to lower the amount of fat in the liver. The study is looking at: * What side effects ALN-CIDEB might cause * How well ALN-CIDEB works to change liver fat, liver injury, and liver scarring * How the body and the liver change after having ALN-CIDEB, which can help researchers understand why ALN-CIDEB works better for some people than others
Interventions
DRUGALN-CIDEB
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. A diagnosis of MASH documented in the participant's medical history, or a clinical suspicion of MASH based on non-invasive biomarkers and clinical risk factors, including having a history of 1 or more elements of metabolic syndrome as described in the protocol 2. Screening percutaneous liver biopsy demonstrating a NAFLD Activity Score (NAS) ≥4 and fibrosis stage F2 or F3 as described in the protocol 3. Has a FibroScan Aspartate aminotransferase (FAST) score \>0.35 either at Screening Visit 1 or within approximately 3 months of Screening Visit 1 as described in the protocol Key
Exclusion criteria
1. Known chronic liver disease other than Metabolic dysfunction-Associated steatotic Liver Disease (MASLD), as determined by the investigator as described in the protocol 2. Prior or current suspected or known drug-induced liver injury within approximately 1 year prior to Screening Visit 1 3. History of liver transplantation, current placement on a liver transplant list, or MELD score \>12 4. Known history of alcohol or other substance abuse within the last year or at any time during screening based on investigator's discretion and/or a score on the AUDIT questionnaire ≥8 5. Prior current, or planned future use of a Glucagon-Like Peptide-1 (GLP-1) receptor agonist-based therapy or any medication approved for the treatment of MASH unless used at a generally stable dose and regimen since at least 3 months prior to Screening Visit 1 or the qualifying historical liver biopsy and throughout the screening period with no change to the dose or regimen anticipated during the treatment period as described in the protocol NOTE: Other Protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent change from baseline in liver fat by Magnetic Resonance Imaging-derived Proton Density Fat Fraction (MRI-PDFF) | At week 26 |
Secondary
| Measure | Time frame |
|---|---|
| Resolution of MASH with no worsening of Nonalcoholic Steatohepatitis-Clinical Research Network (NASH-CRN) fibrosis on liver biopsy | At week 52 |
| Percent change from baseline in liver fat by MRI-PDFF | At week 52 |
| Achievement of a ≥30% reduction in liver fat by MRI-PDFF | At week 52 |
| Achievement of ≤5% liver fat by MRI-PDFF | At week 52 |
| Percent change from baseline in liver fat by MRI-PDFF for each dose level of ALN-CIDEB | Up to week 52 |
| Improvement of NASH-CRN Fibrosis Stage (F) by ≥1 with no worsening of MASH | At week 52 |
| Occurrence of Treatment-Emergent Adverse Events (TEAEs) | Up to week 64 |
| Severity of TEAEs | Up to week 64 |
| Change from baseline in FibroScan Controlled Attenuation Parameter (CAP) | Through week 52 |
| Change from baseline in FibroScan Liver Stiffness Measurement (LSM) by Vibration Controlled Transient Elastography (VCTE) | Through week 52 |
| Change from baseline in Aspartate Aminotransferase (AST) | Up to week 64 |
| Change from baseline in Alanine Aminotransferase (ALT) | Up to week 64 |
| Change from baseline in Enhanced Liver Fibrosis (ELF) | Through week 52 |
| Change from baseline in PRO-C3 | Through week 52 |
| Change from baseline in ADAPT | Through week 52 |
| Change from baseline in NIS2+ | Through week 52 |
| Percent change from baseline in liver fat by MRI-PDFF in genetic subpopulations | At week 52 |
Contacts
CONTACTClinical Trials Administrator
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed