Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Conditions
Keywords
Homozygous PNPLA3-Related MASLD, Fatty Liver Disease, Metabolic Dysfunction-Associated Steatohepatitis (MASH), Non-Alcoholic Fatty Liver Disease (NAFLD), Nonalcoholic Steatohepatitis (NASH)
Brief summary
This study will test a study drug called ALN-PNP with and without another drug that is used for controlling blood sugar, appetite, and weight (for example, tirzepatide), to see if it can help treat MASLD, also known as fatty liver disease. ALN-PNP reduces the amount of Patatin-like phospholipase domain-containing protein 3 (PNPLA3), a protein that liver cells make, which may help decrease liver fat if there is an abnormal PNPLA3 protein. The goal of this study is to understand the effect of ALN-PNP with or without tirzepatide on reducing liver fat. The study is looking at: * How well ALN-PNP with and without tirzepatide works * What side effects ALN-PNP might cause * How much ALN-PNP is in the blood at different times * How the body and the liver change after having ALN-PNP, which can help researchers understand why ALN-PNP works better in some people than others
Interventions
DRUGALN-PNP
Administered per the protocol
DRUGTirzepatide
Administered per the protocol
DRUGPlacebo
Administered per the protocol Placebo matching ALN-PNP
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: Part A and Part B: 1. Homozygous for the PNPLA3 p.I148M genotype 2. Liver fat by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF) ≥15% at visit 3 3. Has a Body Mass Index (BMI) ≥30 to \<45 kg/m\^2 at visit 2 Part A: To be eligible for randomization on study day 1: 1. Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤3 × Upper Limit of Normal (ULN) as described in the protocol 2. On a stable dose of tirzepatide at randomization (≥5 mg weekly) Key
Exclusion criteria
1. Evidence or diagnosis of portal hypertension or cirrhosis from any cause, including cirrhosis due to MASH, as determined by the investigator, based on medical history, clinical assessment, imaging, and/or liver biopsy 2. Known chronic liver disease other than MASLD, as determined by the investigator, as defined in the protocol 3. Contraindications to MRI examinations, including but not limited to persons with MRI-incompatible cardiac pacemaker and implants made of metal, severe claustrophobia, size restrictions 4. Any contraindication listed in the Zepbound® United States Prescribing Information (USPI), as defined in the protocol NOTE: Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent change in liver fat | From baseline at week 24 | Part A |
Secondary
| Measure | Time frame |
|---|---|
| Achievement of liver fat <5% | At weeks 24 and 48 |
| Occurence of Treatment-Emergent Adverse Events (TEAEs) | Through week 60 |
| Severity of TEAEs | Through week 60 |
Contacts
CONTACTClinical Trials Administrator
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed