Health Trials

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

ConditionMetabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-75
SponsorRegeneron Pharmaceuticals

About this trial

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 criteria

Qualifiers

Homozygous for the PNPLA3 p.I148M genotype

Liver fat by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF) ≥15% at visit 3

Has a Body Mass Index (BMI) ≥30 to <45 kg/m² at visit 2

Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤3 × Upper Limit of Normal (ULN) as described in the protocol

Disqualifiers

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

Known chronic liver disease other than MASLD, as determined by the investigator, as defined in the protocol

Contraindications to MRI examinations, including but not limited to persons with MRI-incompatible cardiac pacemaker and implants made of metal, severe claustrophobia, size restrictions

Any contraindication listed in the Zepbound United States Prescribing Information (USPI), as defined in the protocol

Trial design

Treatments tested in this trial

  • ALN-PNP
  • Tirzepatide
  • Placebo

Treatment groups

204 Participants
are divided into 6 treatment groups

6

Treatment groups

See each treatment group below.

Sponsors and collaborators

Regeneron Pharmaceuticals

Lead sponsor

Source ClinicalTrials.gov