Placebo: Administered per the protocol Placebo matching ALN-PNP
Study 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
Eligibility
Sex
ALL
Min age
18 Years
Max age
75 Years
Healthy volunteers
No
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/exclusion criteria apply.
Primary outcome measure(s)
Percent change in liver fat — From baseline at week 24 Part A
Percent change in liver fat — From baseline at week 48 Part B
Trial sites (6)
Facility
City
Region
Status
Southern California Research Center
Coronado
California
Recruiting
California Liver Research Institute
Pasadena
California
Recruiting
Tandem Clinical Research, Plaza II
Metairie
Louisiana
Recruiting
American Research Corporation
Austin
Texas
Recruiting
Advanced Medical Trials
Georgetown
Texas
Recruiting
American Research Corporation at The Texas Liver Institute
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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