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

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.