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

Non-alcoholic Fatty Liver Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03357380
• Other study ID #: NN9931-4381
• Secondary ID: 2017-001193-42U1
• Status: Completed
• Phase: Phase 1
• Start date: November 28, 2017
• Est. completion date: March 20, 2020

Study information

• Verified date: November 2021
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 67
• Est. completion date: March 20, 2020
• Est. primary completion date: March 20, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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)

Related Conditions & MeSH terms

• Digestive System Diseases
• Fatty Liver
• Hepatobiliary Disorders
• Liver Diseases
• Non-alcoholic Fatty Liver Disease

Intervention

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
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.

Locations

Country	Name	City	State
Germany	Novo Nordisk Investigational Site	Mainz
Germany	Novo Nordisk Investigational Site	Neuss

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Flint A, Andersen G, Hockings P, Johansson L, Morsing A, Sundby Palle M, Vogl T, Loomba R, Plum-Mörschel L. Randomised clinical trial: semaglutide versus placebo reduced liver steatosis but not liver stiffness in subjects with non-alcoholic fatty liver di — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in liver stiffness (kPa) assessed by magnetic resonance elastography (MRE)	Measured in KPa	Up to day -20, week 48
Secondary	Change in liver stiffness (kPa) assessed by magnetic resonance elastography (MRE)	Measured in KPa	Up to day -20, week 24
Secondary	Change in liver stiffness (kPa) assessed by magnetic resonance elastography (MRE)	Measured in KPa	Up to day -20, week 72
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Proportion of subjects with at least 15% reduction in liver stiffness assessed by magnetic resonance elastography (MRE)	Number of subjects	Weeks 0 - 24
Secondary	Proportion of subjects with at least 15% reduction in liver stiffness assessed by magnetic resonance elastography (MRE)	Number of subjects	Weeks 0 - 48
Secondary	Proportion of subjects with at least 15% reduction in liver stiffness assessed by magnetic resonance elastography (MRE)	Number of subjects	Weeks 0 - 72
Secondary	Change in visceral adipose tissue (L) assessed by magnetic resonance imaging (MRI)	Measured in L	Up to day -20, week 24
Secondary	Change in visceral adipose tissue (L) assessed by magnetic resonance imaging (MRI)	Measured in L	Up to day -20, week 48
Secondary	Change in visceral adipose tissue (L) assessed by magnetic resonance imaging (MRI)	Measured in L	Up to day -20, week 72
Secondary	Change in abdominal subcutaneous adipose tissue (L) assessed by magnetic resonance imaging (MRI)	Measured in L	Up to day -20, week 24
Secondary	Change in abdominal subcutaneous adipose tissue (L) assessed by magnetic resonance imaging (MRI)	Measured in L	Up to day -20, week 48
Secondary	Change in abdominal subcutaneous adipose tissue (L) assessed by magnetic resonance imaging (MRI)	Measured in L	Up to day -20, week 72
Secondary	Change in Body weight (% and kg)	Measured in kg and %	Week 0, week 48
Secondary	Change in Body weight (% and kg)	Measured in kg and %	Week 0, week 72
Secondary	Change in Waist circumference	Measured in cm	Week 0, week 48
Secondary	Change in Waist circumference	Measured in cm	Week 0, week 72
Secondary	Change in Body mass index (BMI)	Measured in kg/sqm	Week 0, week 48
Secondary	Change in Body mass index (BMI)	Measured in kg/sqm	Week 0, week 72
Secondary	Number of treatment-emergent adverse events (TEAEs)	Count of adverse events	Weeks 0 - 48
Secondary	Number of treatment-emergent adverse events (TEAEs)	Count and % of adverse events	Weeks 0 - 79
Secondary	Number of treatment-emergent hypoglycaemic episodes	Count of episodes	Weeks 0 - 48
Secondary	Number of treatment-emergent hypoglycaemic episodes	Count of episodes	Weeks 0 - 79