ALN-PNP with or without a GLP-1/GIP receptor agonist in adults with PNPLA3-related MASLD

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This Phase 2a trial compares ALN-PNP alone and in combination with tirzepatide versus placebo in adults with homozygous PNPLA3-related MASLD. Participants will be evaluated for changes in liver fat using MRI-PDFF, drug levels in the blood, safety, and how the body responds to treatment. The study includes two parts and requires stable tirzepatide dosing at randomization, with specific eligibility focused on genotype, liver fat, and obesity. Exclusion criteria emphasize absence of cirrhosis, other chronic liver diseases, and MRI contraindications. Lead sponsor is Regeneron, with sites in Arizona and California.

Why it matters

Who can join: the full rules

Key Inclusion Criteria:

Part A and Part B:

1. Homozygous for the PNPLA3 p.I148M genotype
2. Liver fat by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF) ≥15% at visit 3
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:

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

Key Exclusion Criteria:

1. 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
2. Known chronic liver disease other than MASLD, as determined by the investigator, as defined in the protocol
3. Contraindications to MRI examinations, including but not limited to persons with MRI-incompatible cardiac pacemaker and implants made of metal, severe claustrophobia, size restrictions
4. Any contraindication listed in the Zepbound United States Prescribing Information (USPI), as defined in the protocol

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

Where it's running

• Arizona Liver Health - Tucson
  Tucson, Arizona, United States Recruiting
• Southern California Research Center
  Coronado, California, United States Recruiting
• California Liver Research Institute
  Pasadena, California, United States Recruiting
• Health Awareness, Inc
  Jupiter, Florida, United States Recruiting
• Evolution Clinical Trials
  Miami, Florida, United States Recruiting
• Tandem Clinical Research, Plaza II
  Metairie, Louisiana, United States Recruiting

Study contacts

• Study coordinator: Clinical Trials Administrator
• Email: clinicaltrials@regeneron.com
• Phone: 844-734-6643

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

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  Recruiting at 2 sites Phase 4 The Cleveland Clinic · Phoenix, Arizona and 21 other locations · NCT06374875

• ALN-PNP safety and tolerability in healthy adults and adults with MASLD

  This first-in-human trial tests whether the experimental drug ALN-PNP is safe and well tolerated in healthy adults and in adults with MASLD who carry a specific PNPLA3 gene variant.

  Recruiting at 5 sites Phase 1/2 Regeneron Pharmaceuticals · Glendale, California and 5 other locations · NCT05648214

• See if a Mediterranean-style lifestyle program helps MASLD patients improve liver health

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• Exercise for an Aging Liver

  This study tests whether a supervised 12-week exercise program can reduce liver fat, inflammation, and fibrosis in adults with MASLD or at-risk MASH, comparing younger and older adults and different disease severities.

  Recruiting Consorcio Centro de Investigación Biomédica en Red (CIBER) · Madrid, Madrid · NCT07467512

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.