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

Study Overview
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Brief Summary
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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.

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

Conditions
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Hepatobiliary Disorders, Non-alcoholic Fatty Liver Disease

Intervention / Treatment
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* Drug: Semaglutide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Semaglutide<br>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<br>* 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.<br>|
| Placebo Comparator: Placebo<br>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<br>* 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.<br>|

What is the study measuring?
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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 |