Investigation of Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of NNC0581-0001 in Participants With Hepatic Steatosis and Suspected Steatohepatitis
The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of NNC0581-0001 in participants with hepatic steatosis and suspected steatohepatitis (increased liver fat and suspected inflammation). NNC0581-0001 will be given in 2 different dose levels as injection under the skin (once per month for 3 months). Participants will either get NNC0581-001 or Placebo (dummy treatment). Which treatment participants get is decided by chance. NNC0581-0001 is a new medicine which cannot be prescribed by doctors. The study will last about 58 weeks.
• Considered eligible based on the medical history, physical examination, and the results of vital signs, electrocardiogram and clinical laboratory tests performed during the screening visit, as judged by the investigator.
• Male or female (of non-childbearing potential) aged 18-64 years (both inclusive) at the time of signing the informed consent.
• Body mass index (BMI) 25.0 to 39.9 kilogram per square meter (kg/m\^2) (both inclusive) at screening.
• Liver fat content measured by magnetic resonance imaging - estimated proton density fat fraction (MRI-PDFF) greater than or equal to (\>=) 10 percent and liver stiffness greater than 8 kilopascal (kPa) as measured by FibroScan® (vibration-controlled transient elastography \[VCTE™\]).
⁃ Additional inclusion criteria for participants in the open-label liver biopsy cohort apply:
• Alanine aminotransferase (ALT) in men greater than (\>) 30 units per liter (U/L), women \> 19 U/L
• Liverstiffness, measured by FibroScan® (VCTE) \> 8 kPa and less than (\<) 12 kPa
• Informed consent obtained at screening for a liver biopsy to be performed at baseline and post-treatment.
⁃ Note: Participants with confirmed metabolic dysfunction-associated steatohepatitis (MASH), based on a prior liver biopsy, can be included in the open-label cohort.