A Study on How Semaglutide Works on Early Stages of Scar Tissue in the Liver Assessed by Pictures of the Liver

A Trial Investigating the Effect of Subcutaneous Semaglutide on Liver Fibrosis Assessed by Magnetic Resonance Elastography in Subjects With Non-alcoholic Fatty Liver Disease

This study is looking at the effect of semaglutide on subjects with nonalcoholic fatty liver disease.This study is comparing the change in early stages of scar tissue in the liver and fat deposition in the liver in people taking semaglutide and placebo (a dummy medicine).

Participants will either get semaglutide or placebo; which treatment participants get is decided by chance. Semaglutide is a medicine under clinical investigation. That means that the medicine has not yet been approved by the authorities. Participants will need to self-inject medicine once daily for 72 weeks. The medicine should be injected under the skin in the stomach, thigh or upper arm.

There are about 3 weeks before participants start the study medicine and 7 weeks after you stop it. The study will last for about 82 weeks in total.

Participants will have 12 clinic visits, 6 phone calls and 4 visits to an MRI centre.

The study includes MRI scans of the stomach. The MRI scans will take place at a different location. Participants will be excluded from the study if the study doctor thinks that there are risks for participants health. Women cannot take part if pregnant, breast-feeding or plan to become pregnant during the study period.

Study Overview

• Status: Completed
• Conditions: Non-alcoholic Fatty Liver Disease; Hepatobiliary Disorders
• Intervention / Treatment: Drug: Semaglutide; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Mainz, Germany, 55116
    • Novo Nordisk Investigational Site
  • Neuss, Germany, 41460
    • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial
• Male or female, aged 18-75 years (both inclusive) at the time of signing informed consent
• Liver steatosis greater than or equal to 10% measured by magnetic resonance imaging proton density fat fraction at screening
• Liver stiffness between 2.50 and 4.63 kPa (both inclusive) measured by magnetic resonance elastography at screening
• Body mass index between 25.0 and 40.0 kg/sqm (both inclusive) at the screening visit

Exclusion Criteria:

• Known or suspected abuse of alcohol (greater than 12 g/day for women or greater than 24 g/day for men) or alcohol dependence assessed by the Alcohol Use Disorders Identification Test (AUDIT questionnaire)
• Diagnosis of type 1 diabetes according to medical records
• Glycosylated haemoglobin A1c (HbA1c) greater than 9.5% at screening
• History or presence of pancreatitis (acute or chronic) as declared by the subject
• Screening calcitonin greater than or equal to 100 ng/L
• Personal or first degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma (as declared by the subject)
• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using highly effective contraceptive methods. (Highly effective contraceptive methods are considered those with a failure rate less than 1% undesired pregnancies per year including surgical sterilisation, hormonal intrauterine devices (coil), oral hormonal contraceptives, sexual abstinence (only acceptable if corresponding to the preferred and usual lifestyle of the subject) or a surgically sterilised partner)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Semaglutide; Semaglutide will be initiated with a starting dose of 0.05 mg/day for the first 4 weeks. The dose will be increased every 4 weeks until the target dose of 0.4 mg/day has been reached.	Drug: Semaglutide; Subcutaneously (under the skin) once-daily. Will be increased more or less every 4 weeks. It is expected that from week 16 until week 72 The participants take the maximum planned dose (0.4 mg) of study medicine.
PLACEBO_COMPARATOR: Placebo; Placebo will be initiated with a starting volume corresponding to 0.05 mg/day of semaglutide for the first 4 weeks. The volume will then be increased every 4 weeks until the target volume corresponding to 0.4 mg/day of semaglutide has been reached.	Drug: Placebo; Subcutaneously (under the skin) once-daily. Will be increased more or less every 4 weeks. It is expected that from week 16 until week 72 The participants take the maximum planned dose (0.4 mg) of study medicine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in liver stiffness (kPa) assessed by magnetic resonance elastography (MRE)	Measured in KPa	Up to day -20, week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in liver stiffness (kPa) assessed by magnetic resonance elastography (MRE)	Measured in KPa	Up to day -20, week 24
Change in liver stiffness (kPa) assessed by magnetic resonance elastography (MRE)	Measured in KPa	Up to day -20, week 72
Change in relative liver fat content (%) assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF)	Measured in Percentage (%)	Up to day -20, week 24
Change in relative liver fat content (%) assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF)	Measured in Percentage (%)	Up to day -20, week 48
Change in relative liver fat content (%) assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF)	Measured in Percentage (%)	Up to day -20, week 72
Change in absolute liver fat volume (L) assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF)	Measured in Percentage (%)	Up to day -20, week 24
Change in absolute liver fat volume (L) assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF)	Measured in L	Up to day -20, week 48
Change in absolute liver fat volume (L) assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF)	Measured in L	Up to day -20, week 72
Proportion of subjects with at least 30% reduction in relative liver fat content assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF)	Number of subjects	Weeks 0 - 24
Proportion of subjects with at least 30% reduction in relative liver fat content assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF)	Number of subjects	Weeks 0 - 48
Proportion of subjects with at least 30% reduction in relative liver fat content assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF)	Number of subjects	Weeks 0 - 72
Proportion of subjects with at least 15% reduction in liver stiffness assessed by magnetic resonance elastography (MRE)	Number of subjects	Weeks 0 - 24
Proportion of subjects with at least 15% reduction in liver stiffness assessed by magnetic resonance elastography (MRE)	Number of subjects	Weeks 0 - 48
Proportion of subjects with at least 15% reduction in liver stiffness assessed by magnetic resonance elastography (MRE)	Number of subjects	Weeks 0 - 72
Change in visceral adipose tissue (L) assessed by magnetic resonance imaging (MRI)	Measured in L	Up to day -20, week 24
Change in visceral adipose tissue (L) assessed by magnetic resonance imaging (MRI)	Measured in L	Up to day -20, week 48
Change in visceral adipose tissue (L) assessed by magnetic resonance imaging (MRI)	Measured in L	Up to day -20, week 72
Change in abdominal subcutaneous adipose tissue (L) assessed by magnetic resonance imaging (MRI)	Measured in L	Up to day -20, week 24
Change in abdominal subcutaneous adipose tissue (L) assessed by magnetic resonance imaging (MRI)	Measured in L	Up to day -20, week 48
Change in abdominal subcutaneous adipose tissue (L) assessed by magnetic resonance imaging (MRI)	Measured in L	Up to day -20, week 72
Change in Body weight (% and kg)	Measured in kg and %	Week 0, week 48
Change in Body weight (% and kg)	Measured in kg and %	Week 0, week 72
Change in Waist circumference	Measured in cm	Week 0, week 48
Change in Waist circumference	Measured in cm	Week 0, week 72
Change in Body mass index (BMI)	Measured in kg/sqm	Week 0, week 48
Change in Body mass index (BMI)	Measured in kg/sqm	Week 0, week 72
Number of treatment-emergent adverse events (TEAEs)	Count of adverse events	Weeks 0 - 48
Number of treatment-emergent adverse events (TEAEs)	Count and % of adverse events	Weeks 0 - 79
Number of treatment-emergent hypoglycaemic episodes	Count of episodes	Weeks 0 - 48
Number of treatment-emergent hypoglycaemic episodes	Count of episodes	Weeks 0 - 79

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Flint A, Andersen G, Hockings P, Johansson L, Morsing A, Sundby Palle M, Vogl T, Loomba R, Plum-Morschel L. Randomised clinical trial: semaglutide versus placebo reduced liver steatosis but not liver stiffness in subjects with non-alcoholic fatty liver disease assessed by magnetic resonance imaging. Aliment Pharmacol Ther. 2021 Nov;54(9):1150-1161. doi: 10.1111/apt.16608. Epub 2021 Sep 27.
• Andersen G, Plum-Morschel L, Hockings PD, Morsing A, Palle MS, Svolgaard O, Flint A. Clinical Characteristics of a Non-Alcoholic Fatty Liver Disease Population Across the Fibrosis Spectrum Measured by Magnetic Resonance Elastography: Analysis of Screening Data. Adv Ther. 2020 Dec;37(12):4866-4876. doi: 10.1007/s12325-020-01503-x. Epub 2020 Oct 1.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 28, 2017
• Primary Completion (ACTUAL): March 20, 2020
• Study Completion (ACTUAL): March 20, 2020

Study Registration Dates

• First Submitted: November 23, 2017
• First Submitted That Met QC Criteria: November 23, 2017
• First Posted (ACTUAL): November 29, 2017

Study Record Updates

• Last Update Posted (ACTUAL): November 22, 2021
• Last Update Submitted That Met QC Criteria: November 12, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Digestive System Diseases
• Other Study ID Numbers: NN9931-4381; 2017-001193-42 (REGISTRY: European Medicines Agency (EudraCT)); U1111-1194-3900 (OTHER: 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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes