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NCT Number: NCT07527910

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

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

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Key information

Conditions

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Digestive System Diseases Fatty Liver Liver Diseases Non-alcoholic Fatty Liver Disease

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Southern California Research Center, Coronado, California, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

Part A and Part B:

  • 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/m^2 at visit 2

Part A: To be eligible for randomization on study day 1:

  • Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤3 × Upper Limit of Normal (ULN) as described in the protocol
  • On a stable dose of tirzepatide at randomization (≥5 mg weekly)

Key Exclusion Criteria:

  • 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

NOTE: Other protocol-defined inclusion/exclusion criteria apply.

Treatment and study plan

ALN-PNP

Drug

Administered per the protocol

Tirzepatide

Drug

Administered per the protocol

Other names: Zepbound®

Placebo

Drug

Administered per the protocol Placebo matching ALN-PNP

Primary outcomes

  1. Percent change in liver fat

    Time frame: From baseline at week 24

    Part A

  2. Percent change in liver fat

    Time frame: From baseline at week 48

    Part B

Secondary outcomes

  1. Achievement of liver fat <5%

    Time frame: At weeks 24 and 48

  2. Occurrence of Treatment-Emergent Adverse Events (TEAEs)

    Time frame: Through week 72

  3. Severity of TEAEs

    Time frame: Through week 72

Study contacts

Contact information is provided by the study sponsor or research team.

Clinical Trials Administrator

CONTACT

[email protected]

844-734-6643

Sponsors and collaborators

Lead sponsor

Regeneron Pharmaceuticals

Industry

Registry information

Official study title

A Two-Part, Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study of ALN-PNP With and Without a GLP1R Agonist in Adults With Homozygous PNPLA3-Related Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Important dates

Study start
2026
Primary completion
2030
Study completion
2030
First posted
Apr 14, 2026
Registry last updated
Jun 26, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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