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

Primary Purpose

Hepatobiliary Disorders, Non-alcoholic Fatty Liver Disease

Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Semaglutide
Placebo
Sponsored by
Novo Nordisk A/S
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatobiliary Disorders

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Semaglutide

Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Change in liver stiffness (kPa) assessed by magnetic resonance elastography (MRE)
Measured in KPa

Secondary Outcome Measures

Change in liver stiffness (kPa) assessed by magnetic resonance elastography (MRE)
Measured in KPa
Change in liver stiffness (kPa) assessed by magnetic resonance elastography (MRE)
Measured in KPa
Change in relative liver fat content (%) assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF)
Measured in Percentage (%)
Change in relative liver fat content (%) assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF)
Measured in Percentage (%)
Change in relative liver fat content (%) assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF)
Measured in Percentage (%)
Change in absolute liver fat volume (L) assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF)
Measured in Percentage (%)
Change in absolute liver fat volume (L) assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF)
Measured in L
Change in absolute liver fat volume (L) assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF)
Measured in L
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
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
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
Proportion of subjects with at least 15% reduction in liver stiffness assessed by magnetic resonance elastography (MRE)
Number of subjects
Proportion of subjects with at least 15% reduction in liver stiffness assessed by magnetic resonance elastography (MRE)
Number of subjects
Proportion of subjects with at least 15% reduction in liver stiffness assessed by magnetic resonance elastography (MRE)
Number of subjects
Change in visceral adipose tissue (L) assessed by magnetic resonance imaging (MRI)
Measured in L
Change in visceral adipose tissue (L) assessed by magnetic resonance imaging (MRI)
Measured in L
Change in visceral adipose tissue (L) assessed by magnetic resonance imaging (MRI)
Measured in L
Change in abdominal subcutaneous adipose tissue (L) assessed by magnetic resonance imaging (MRI)
Measured in L
Change in abdominal subcutaneous adipose tissue (L) assessed by magnetic resonance imaging (MRI)
Measured in L
Change in abdominal subcutaneous adipose tissue (L) assessed by magnetic resonance imaging (MRI)
Measured in L
Change in Body weight (% and kg)
Measured in kg and %
Change in Body weight (% and kg)
Measured in kg and %
Change in Waist circumference
Measured in cm
Change in Waist circumference
Measured in cm
Change in Body mass index (BMI)
Measured in kg/sqm
Change in Body mass index (BMI)
Measured in kg/sqm
Number of treatment-emergent adverse events (TEAEs)
Count of adverse events
Number of treatment-emergent adverse events (TEAEs)
Count and % of adverse events
Number of treatment-emergent hypoglycaemic episodes
Count of episodes
Number of treatment-emergent hypoglycaemic episodes
Count of episodes

Full Information

First Posted
November 23, 2017
Last Updated
November 12, 2021
Sponsor
Novo Nordisk A/S
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1. Study Identification

Unique Protocol Identification Number
NCT03357380
Brief Title
A Study on How Semaglutide Works on Early Stages of Scar Tissue in the Liver Assessed by Pictures of the Liver
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
November 28, 2017 (Actual)
Primary Completion Date
March 20, 2020 (Actual)
Study Completion Date
March 20, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novo Nordisk A/S

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatobiliary Disorders, Non-alcoholic Fatty Liver Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Sponsor staff involved in the clinical trial is masked according to company standard procedures
Allocation
Randomized
Enrollment
67 (Actual)

8. Arms, Groups, and Interventions

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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Reporting Anchor and Disclosure (1452)
Organizational Affiliation
Novo Nordisk A/S
Official's Role
Study Director
Facility Information:
Facility Name
Novo Nordisk Investigational Site
City
Mainz
ZIP/Postal Code
55116
Country
Germany
Facility Name
Novo Nordisk Investigational Site
City
Neuss
ZIP/Postal Code
41460
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
IPD Sharing URL
http://novonordisk-trials.com/website/content/how-to-access-clinical-trial-datasets.aspx
Citations:
PubMed Identifier
34570916
Citation
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.
Results Reference
result
PubMed Identifier
33006125
Citation
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.
Results Reference
derived

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

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