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

What Was Tested

This registered phase 2 trial tested Tirzepatide.

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.

It had six arms (groups): Part A: A1 (experimental), Part A: A2 (experimental), Part B: B1 (experimental), Part B: B2 (experimental) and Part B: B3 (experimental).

The registry classes the interventions as drug.

Who Took Part

204 planned participants were the target.

It was open to people of any sex aged from 18 years up to 75 years.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: Homozygous for the PNPLA3 p.I148M genotype. Has a Body Mass Index (BMI) ≥30 to \<45 kg/m\^2 at visit 2. Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤3 × Upper Limit of Normal (ULN) as described in the protocol.

The full record lists 5 inclusion and 4 exclusion criteria; among the exclusions: 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.

How the Study Was Run

Design: randomized, parallel-group and quadruple-blind.

Because people in this Tirzepatide study were split into groups at random, differences between the groups are less likely to reflect who happened to join each one.

The Tirzepatide group and the comparison group ran side by side rather than switching.

Neither the participants nor the staff measuring them knew who was on Tirzepatide, so expectations could not easily colour the readings.

Those kept unaware of assignments: participant, care provider, investigator and outcomes assessor.

It started in 2026-05-22 with completion listed for 2030-03-15.

It ran at 9 sites in United States (9).

Its stated primary purpose is treatment.

What Was Measured

Primary outcome: Percent change in liver fat (time frame: From baseline at week 24). Percent change in liver fat (time frame: From baseline at week 48).

It also tracked 3 secondary outcomes, for example Occurrence of Treatment-Emergent Adverse Events (TEAEs) and Severity of TEAEs.

What This Means in Plain Language

Put simply, this is a phase 2, randomized trial of Tirzepatide in 204 people.

It is still recruiting; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the Tirzepatide compound page, all human trials.