Metabolic Dysfunction-Associated Steatohepatitis, Metabolic Dysfunction-Associated Steatotic Liver Disease
Conditions
Keywords
Obese, MASLD, MASH
Brief summary
This study is researching an experimental drug called ALN-CIDEB, also referred to as "study drug". The study is focused on participants with metabolic dysfunction-associated steatotic liver disease (MASLD) (Part A) and metabolic dysfunction-associated steatohepatitis (MASH) (Part B). MASLD and MASH are long-lasting liver conditions caused by having too much fat in the liver. The aim of the study is to see how safe and tolerable the study drug is. The study is looking at several other research questions, including: * What side effects may happen from taking the study drug * How the study drug works to change liver fat content * How much study drug and study drug metabolites (byproducts of the body breaking down the study drug) are in the blood at different times
Interventions
DRUGALN-CIDEB
Administered per the protocol
DRUGPlacebo
Administered per the protocol
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Phase 1 (ex-US), Phase 1/2a (US only), Part A: Sequential and Part B: Parallel
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Part A: 18 to 55 years at Screening Visit 1 with MASLD, at Screening Visit 1 Part B: 18 to 65 years at Screening Visit 1 with a diagnosis of MASH, at Screening Visit 1 2. Body Mass Index (BMI) ≥30 kg/m2 and ≤40 kg/m2 at Screening Visit 1 3. Controlled-Attenuation Parameter (CAP) ≥285 dB/m by FibroScan during screening as described in the protocol 4. Liver fat content ≥8.5% by MRI-PDFF during screening 5. If on anti-hypertensive and/or lipid lowering medications and/or glucose lowering medications, must be on generally stable dose(s) for at least 12 weeks prior to screening and no changes to the dose(s) are anticipated during the study 6. Part B: A diagnosis of MASH documented in the participant's medical history, or a clinical suspicion of MASH based on non-invasive biomarkers (eg, evidence of fatty liver on imaging and elevated liver enzymes) and clinical risk factors, including having a history of 2 or more elements of metabolic syndrome, as defined in the protocol 7. Part B: Screening percutaneous liver biopsy NAFLD Activity Score (NAS) ≥3 and fibrosis stage, as defined in the protocol Key
Exclusion criteria
1. Known historical or current diagnosis of portal hypertension or cirrhosis based on clinical assessment, imaging, and/or liver biopsy 2. Known historical or current diagnosis of other forms of chronic liver disease, as defined in the protocol 3. Prior or current suspected or known drug-induced liver injury within 1 year prior to screening 4. History of liver transplant, current placement on a liver transplant list, or Model for End-stage Liver Disease (MELD) score \>12 5. Contraindication to MRI examinations, such as persons with cardiac pacemaker and implants made of metal, severe claustrophobia, size restrictions, or other contraindications for MRI 6. Liver stiffness measurement, laboratory parameter assessment, estimated Glomerular Filtration Rate (GFR), and evidence of uncontrolled hypertension, as defined in the protocol 7. Evidence of Human Immunodeficiency Virus (HIV) infection, Hepatitis B Virus (HBV) infection, or Hepatitis C Virus (HCV) infection during screening, as described in the protocol 8. History of Type 1 Diabetes 9. Bariatric surgery, including any procedures to revise, reverse, or remove any previous bariatric surgery interventions, within approximately 5 years prior to randomization or planned during the study period NOTE: Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Treatment-Emergent Adverse Events (TEAEs) | Up to 48 Weeks |
| Severity of TEAEs | Up to 48 Weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in liver fat fraction by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF) | Baseline up to 48 Weeks | — |
| Total concentration of ALN-CIDEB in plasma | Up to 48 Weeks | — |
| Total concentration of potential major metabolite(s) in plasma | Up to 48 Weeks | — |
| Urinary recovery of ALN-CIDEB as a proportion of the dose | Up to 36 Weeks | Part A |
| Urinary recovery of potential major metabolite(s) as a proportion of the dose | Up to 36 Weeks | Part A |
| Change in Aspartate Aminotransferase (AST) | Baseline up to 48 Weeks | — |
| Change in Alanine Aminotransferase (ALT) | Baseline up to 48 Weeks | — |
| Change in hepatic Cell death-Inducing DNA fragmentation factor alpha-like Effector B (CIDEB) messenger RiboNucleic Acid (mRNA) level | Baseline up to 36 Weeks | Part B |
Countries
United Kingdom, United States
Contacts
CONTACTClinical Trials Administrator
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed