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

Purpose

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

Condition

  • Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Eligibility

Eligible Ages
Between 18 Years and 75 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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)

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.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Part A: A1
  • Drug: ALN-PNP
    Administered per the protocol
  • Drug: Tirzepatide
    Administered per the protocol
    Other names:
    • Zepbound®
Experimental
Part A: A2
  • Drug: Tirzepatide
    Administered per the protocol
    Other names:
    • Zepbound®
  • Drug: Placebo
    Administered per the protocol Placebo matching ALN-PNP
Experimental
Part B: B1
  • Drug: ALN-PNP
    Administered per the protocol
  • Drug: Tirzepatide
    Administered per the protocol
    Other names:
    • Zepbound®
Experimental
Part B: B2
  • Drug: Tirzepatide
    Administered per the protocol
    Other names:
    • Zepbound®
  • Drug: Placebo
    Administered per the protocol Placebo matching ALN-PNP
Experimental
Part B: B3
  • Drug: ALN-PNP
    Administered per the protocol
Placebo Comparator
Part B: B4
  • Drug: Placebo
    Administered per the protocol Placebo matching ALN-PNP

Recruiting Locations

Southern California Research Center
Coronado, California 92118

California Liver Research Institute
Pasadena, California 91105

Tandem Clinical Research, Plaza II
Metairie, Louisiana 70006

Advanced Medical Trials
Georgetown, Texas 78628

American Research Corporation at The Texas Liver Institute
San Antonio, Texas 78215

More Details

Status
Recruiting
Sponsor
Regeneron Pharmaceuticals

Study Contact

Clinical Trials Administrator
844-734-6643
clinicaltrials@regeneron.com