Phase 2a Study of ALN-PNP With or Without GLP1R Agonist to Treat MASLD in Adults With PNPLA3 Gene Variation

What this Trial Is About

Researchers are evaluating the study drug ALN-PNP, with and without another drug called tirzepatide, to see if they can help treat Metabolic Dysfunction-Associated Steatotic Liver Disease MASLD, also known as fatty liver disease. ALN-PNP works by reducing a protein called PNPLA3 that liver cells produce, which may decrease liver fat when this protein is abnormal. The goal is to understand the effects of ALN-PNP alone and combined with tirzepatide on reducing liver fat. Participants will receive ALN-PNP with or without tirzepatide, or a placebo matching ALN-PNP, following a randomized and double-blind design. The study includes different groups and is conducted in two parts. Treatments are administered according to the study protocol, and the effects of these drugs on liver fat and other health measures will be compared over time. During the study, participants will be monitored regularly with assessments including liver fat measurements by MRI, blood tests to track drug levels, and safety evaluations to record any side effects. The main outcomes measured are the percentage change in liver fat at 24 and 48 weeks. Additional monitoring of side effects will continue through week 72. The total study duration extends up to March 2030.

A Phase 2a Study of ALN-PNP With and Without a GLP1R Agonist in Adult Patients With Homozygous PNPLA3-Related MASLD