A Trial to Evaluate the Efficacy and Safety of ARO-INHBE in Adults With Metabolic Dysfunction-Associated Steatohepatitis

Prior treatment

• Use of non-GLP-1 receptor medications known to cause weight loss within 3 months prior to Screening.
• Use of medications associated with weight gain (for example, tricyclic antidepressants, mirtazapine, paroxetine, atypical antipsychotics) unless on a stable dose ≥3 months prior to Screening with anticipated continuation on this dose throughout the trial.
• Major surgery within 90 days of Screening.
• Use of hepatocyte-targeted ribonucleic acid interference (RNAi) therapies within 6 months of Screening.

Other illness

• History or evidence of hepatic disease of non-metabolic dysfunction-associated steatotic liver disease (MASLD) etiology (viral hepatitis, alcoholic liver disease, primary biliary cholangitis \[PBC\], primary sclerosing cholangitis \[PSC\], Wilson's disease, alpha-1 antitrypsin \[A1AT\] deficiency, hemochromatosis, or autoimmune hepatitis).
• Type 1 diabetes mellitus (T1DM) or uncontrolled Type 2 diabetes mellitus (T2DM).
• Clinically significant end-organ disease.

Lab values

• Clinical or laboratory signs of decompensated liver disease, history of esophageal varices, ascites, or hepatic encephalopathy, or history of cirrhosis on biopsy performed prior to Screening.

Other

• Insulin use within 6 months of Screening (except short-term peri-procedural/inpatient use).
  • Note: Other protocol-defined Inclusion/Exclusion criteria may apply.

• BMI between 30.0 to 50.0 kilograms (kg)/square meter (m\^2) (inclusive) with body weight ≤159 kg at Screening
• Stable body weight
• Participants on background glucagon-like peptide-1 (GLP-1) (or GLP-1/glucose-dependent insulinotropic polypeptide \[GIP\]) therapy must be on a stable dose for ≥6 months
• Participants not on GLP-1 (or GLP-1/GIP) therapy must be treatment naïve or off therapy for ≥6 months.