A Study to Assess the Safety, Efficacy, and Pharmacokinetics of Multiple Doses of ION224

Inclusion Criteria: * Males or females greater than or equal to (≥) 18 and less than or equal to (≤) 75 years old at the time of informed consent * Body mass index ≥ 25 kg/m\^2 and ≥ 22 kg/m\^2 for participants of Asian race, as assessed during screening * Liver fat ≥ 10% as assessed by MRI-PDFF before randomization * Presence of NASH confirmed by centrally read liver biopsy * Weight loss \< 5% after historical biopsy. Otherwise, weight loss \< 5% in the previous 3 months prior to randomization * ALT and AST ≤ 200 units per liter (U/L) and confirmed to be stable * Total Bilirubin ≤ 1.3 milligrams per deciliter (mg/dL) and confirmed to be stable Exclusion Criteria: * Prior or planned (during the Study Period) bariatric surgery or previous bariatric surgery within 2 years prior to screening * History of solid organ transplant * Screening laboratory values that would render a participant unsuitable for inclusion, including but not limited to: * Clinically significant albuminuria or proteinuria * Positive test for blood on urinalysis * Estimated glomerular filtration rate (eGFR) \< 60 milliliters (mL)/minute (min)/1.73 square meter (m\^2) * Hemoglobin A1c (HbA1c) \> 9.5% * Platelet count \< 170 × 10\^9/liter (L) * Diagnosis of Gilbert's syndrome * Known history of or evidence of liver disease other than NASH * Clinical evidence of liver decompensation * Active SARS-CoV-2 infection (COVID-19) or confirmed SARS-CoV-2 infection-related complication within 8 weeks of Screening * Uncontrolled arterial hypertension * History of bleeding diathesis or coagulopathy * Participants with known intolerance to magnetic resonance imaging (MRI) or with conditions contraindicated for MRI Procedures * History of, or current hard drug or alcohol abuse within 2 years prior to Screening * Use of drugs historically associated with NAFLD for more than 2 weeks in the year prior to Screening * Use of obeticholic acid, ursodeoxycholic acid, icosapent ethyl, niacin, PCSK9 inhibitors, and bile acid sequestrants * Participants taking the following medicines UNLESS on a stable dose: * Anti-diabetic medications * statins, fenofibrate, and ezetimibe * Estrogen containing contraceptives * Glucagon-like peptide (GLP)-1 agonists * Pioglitazone * Vitamin E at doses ≤ 800 international unit (IU)/day * Herbal medicines, other prescription medicines, vitamins or supplements known to affect lipid metabolism * Other protocol-defined inclusion/exclusion criteria could apply