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

Phase 1

Recruiting

• Conditions: Healthy Volunteers; Hepatic Steatosis
• Interventions: Drug: NNC0581-0001; Drug: Placebo (NNC0581-0001)

• Registration Number: NCT06891365
• Lead Sponsor: Novo Nordisk A/S

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-03
• Study Start: 2025-03-12
• Study First Submitted: 2025-03-17
• Study First Submitted QC: 2025-03-17
• Last Update Submitted: 2025-03-17
• Study First Posted: 2025-03-24
• Last Update Posted: 2025-03-24
• Primary Completion: 2027-01-25
• Study Completion: 2027-01-25

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 48

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1: NNC0581-0001 (Dose 1)	NNC0581-0001	Participants will receive a subcutaneous (s.c) injection of either NNC0581-0001 Dose 1 or a matching placebo once monthly.
Cohort 1: NNC0581-0001 (Dose 1)	Placebo (NNC0581-0001)	Participants will receive a subcutaneous (s.c) injection of either NNC0581-0001 Dose 1 or a matching placebo once monthly.
Cohort 2: NNC0581-0001 (Dose 2)	Placebo (NNC0581-0001)	Participants will receive a s.c injection of either NNC0581-0001 Dose 2 or a matching placebo once monthly.
Cohort 2: NNC0581-0001 (Dose 2)	NNC0581-0001	Participants will receive a s.c injection of either NNC0581-0001 Dose 2 or a matching placebo once monthly.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Parexel CPRU, Level 7; 🇬🇧 Harrow, United Kingdom