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Recruiting NCT07527910

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

Phase II Interventional Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: ALN-PNP, Tirzepatide, Placebo.
Who it may be relevant to
Registry conditions: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Basic parameters: 18 years — 75 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official 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)

Overview

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

Interventions

  • Drug ALN-PNP
    Administered per the protocol
  • Drug Tirzepatide
    Administered per the protocol
  • Drug Placebo
    Administered per the protocol Placebo matching ALN-PNP

Primary outcome measures

  • Percent change in liver fat [Time frame: From baseline at week 24]
  • Percent change in liver fat [Time frame: From baseline at week 48]
Secondary outcome measures (3)
  • Achievement of liver fat <5% [Time frame: At weeks 24 and 48]
  • Occurrence of Treatment-Emergent Adverse Events (TEAEs) [Time frame: Through week 72]
  • Severity of TEAEs [Time frame: Through week 72]

Eligibility criteria

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)

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Quadruple blind
Primary purpose
Treatment

Study locations

United States · 5 centers
  • Southern California Research Center — Coronado
  • California Liver Research Institute — Pasadena
  • Tandem Clinical Research, Plaza II — Metairie
  • Advanced Medical Trials — Georgetown
  • American Research Corporation at The Texas Liver Institute — San Antonio

Identifiers

NCT: NCT07527910 · ALN-PNP-MASLD-2543

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗