Clinical trial NCT06891365: Multiple Dose Study for a New Medication to Potentially Treat Liver Diseases
Official title: Investigation of Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of NNC0581-0001 in Participants With Hepatic Steatosis and Suspected Steatohepatitis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Healthy Volunteers
Hepatic Steatosis
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2025-03-24
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* Any disorder, which in the investigator's opinion might jeopardise participant's safety or compliance with the protocol.
* Any laboratory safety parameter, at screening, outside the extended laboratory ranges, and considered clinically significant per the principal investigator (see laboratory provided reference ranges for specific values). Of note, re-screening or re-sampling is NOT allowed if the individual has failed one of the exclusion criteria related to the following laboratory parameters:
* ALT \>= 3 × upper limit of normal (ULN)
* Aspartate aminotransferase (AST) \>= 3 × ULN
* Bilirubin \> 1.5 × ULN
* Estimated glomerular filtration rate (eGFR) \< 60 milliliter per minute per 1.73 square meters (mL/min/1.73 m\^2) at screening.

Primary outcomes:
measure: Number of treatment emergent adverse events (TEAEs)
timeFrame: From 1st dose (day 1) until completion of the end of study visit at week 52
Secondary outcomes:
measure: AUC0-32h: The area under the NNC0581-0001 plasma concentration-time curve from time zero to 32 hours after each of the three doses
timeFrame: From dosing (day 1 in each treatment period) to 32 hours post dose
measure: Cmax: The maximum concentration of NNC0581-0001 in plasma after each dose of three doses
timeFrame: From dosing (day 1 in each treatment period) to 32 hours post dose
measure: Tmax: The time from dose administration to maximum plasma concentration of NNC0581-0001 after each dose of three doses
timeFrame: From dosing (day 1 in each treatment period) to 32 hours post dose
Other outcomes:
Locations:
city: Harrow
country: United Kingdom
facility: Parexel CPRU, Level 7
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (dept. 2834)
role: STUDY_DIRECTOR
References: