Multiple Dose Study for a New Medication to Potentially Treat Liver Diseases

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.

Study Overview

• Status: Recruiting
• Conditions: Healthy Volunteers; Hepatic Steatosis
• Intervention / Treatment: Drug: NNC0581-0001; Drug: Placebo (NNC0581-0001)

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Novo Nordisk; Phone Number: (+1) 866-867-7178; Email: clinicaltrials@novonordisk.com

Study Locations

• United Kingdom
  • Harrow, United Kingdom, HA1 3UJ
    • Recruiting
    • Parexel Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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 18-69 years (both inclusive) at the time of signing the informed consent.
• Body mass index (BMI) greater than or equal to (>=) 25.0 at screening.
• Liver fat content measured by magnetic resonance imaging - estimated proton density fat fraction (MRI-PDFF) >= 10 percent at screening.

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) < 50 milliliter per minute per 1.73 square meters (mL/min/1.73 m^2) at screening.

Additional exclusion criteria for participants in the open-label liver biopsy group apply:

• Medical history of abnormal bleeding
• BMI > 34.9 kilograms per square meters (kg/m^2)
• Presence of ascites
• Cirrhosis based on screening tests or historical biopsy
• Lab abnormalities of platelets count < 150 × 10^9 per liter or International Normalized Ratio (INR) > 1.2
• Concomitant use of medication:
• anticoagulants or herbal supplements with an anticoagulative effect (as judged by the principal investigator)
• antiplatelet medications
• exception for aspirin that must be stopped 5 days prior to procedure and Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) that must not be taken within 3 days of the procedure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: NNC0581-0001 (Dose 1); Participants will receive a subcutaneous (s.c) injection of either NNC0581-0001 Dose 1 or a matching placebo once monthly.	Drug: NNC0581-0001; NNC0581-0001 will be administered subcutaneously.; Drug: Placebo (NNC0581-0001); Placebo matched to NNC0581-0001 will be administered subcutaneously.
Experimental: Cohort 2: NNC0581-0001 (Dose 2); Participants will receive a s.c injection of either NNC0581-0001 Dose 2 or a matching placebo once monthly.	Drug: NNC0581-0001; NNC0581-0001 will be administered subcutaneously.; Drug: Placebo (NNC0581-0001); Placebo matched to NNC0581-0001 will be administered subcutaneously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of treatment emergent adverse events (TEAEs)	Measured as count of events.	From 1st dose (day 1) until completion of the end of study visit at week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-32h: The area under the NNC0581-0001 plasma concentration-time curve from time zero to 32 hours after each of the three doses	Measured in nanogram hour per mililitre (ng*h/mL).	From dosing (day 1 in each treatment period) to 32 hours post dose
Cmax: The maximum concentration of NNC0581-0001 in plasma after each dose of three doses	Measured in nanogram per mililitre(ng/mL).	From dosing (day 1 in each treatment period) to 32 hours post dose
Tmax: The time from dose administration to maximum plasma concentration of NNC0581-0001 after each dose of three doses	Measured in hours.	From dosing (day 1 in each treatment period) to 32 hours post dose

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency (dept. 2834), Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2025
• Primary Completion (Estimated): October 11, 2027
• Study Completion (Estimated): November 15, 2027

Study Registration Dates

• First Submitted: March 17, 2025
• First Submitted That Met QC Criteria: March 17, 2025
• First Posted (Actual): March 24, 2025

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver
• Other Study ID Numbers: NN6581-4981; U1111-1298-9628 (Other Identifier: World Health Organization (WHO))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No