Clinical trial NCT03357380: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatobiliary Disorders
Non-alcoholic Fatty Liver Disease
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2017-11-29
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: Change in liver stiffness (kPa) assessed by magnetic resonance elastography (MRE)
timeFrame: Up to day -20, week 48
Secondary outcomes:
measure: Change in liver stiffness (kPa) assessed by magnetic resonance elastography (MRE)
timeFrame: Up to day -20, week 24
measure: Change in liver stiffness (kPa) assessed by magnetic resonance elastography (MRE)
timeFrame: Up to day -20, week 72
measure: Change in relative liver fat content (%) assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF)
timeFrame: Up to day -20, week 24
measure: Change in relative liver fat content (%) assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF)
timeFrame: Up to day -20, week 48
measure: Change in relative liver fat content (%) assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF)
timeFrame: Up to day -20, week 72
measure: Change in absolute liver fat volume (L) assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF)
timeFrame: Up to day -20, week 24
measure: Change in absolute liver fat volume (L) assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF)
timeFrame: Up to day -20, week 48
measure: Change in absolute liver fat volume (L) assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF)
timeFrame: Up to day -20, week 72
measure: Proportion of subjects with at least 30% reduction in relative liver fat content assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF)
timeFrame: Weeks 0 - 24
measure: Proportion of subjects with at least 30% reduction in relative liver fat content assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF)
timeFrame: Weeks 0 - 48
measure: Proportion of subjects with at least 30% reduction in relative liver fat content assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF)
timeFrame: Weeks 0 - 72
measure: Proportion of subjects with at least 15% reduction in liver stiffness assessed by magnetic resonance elastography (MRE)
timeFrame: Weeks 0 - 24
measure: Proportion of subjects with at least 15% reduction in liver stiffness assessed by magnetic resonance elastography (MRE)
timeFrame: Weeks 0 - 48
measure: Proportion of subjects with at least 15% reduction in liver stiffness assessed by magnetic resonance elastography (MRE)
timeFrame: Weeks 0 - 72
measure: Change in visceral adipose tissue (L) assessed by magnetic resonance imaging (MRI)
timeFrame: Up to day -20, week 24
measure: Change in visceral adipose tissue (L) assessed by magnetic resonance imaging (MRI)
timeFrame: Up to day -20, week 48
measure: Change in visceral adipose tissue (L) assessed by magnetic resonance imaging (MRI)
timeFrame: Up to day -20, week 72
measure: Change in abdominal subcutaneous adipose tissue (L) assessed by magnetic resonance imaging (MRI)
timeFrame: Up to day -20, week 24
measure: Change in abdominal subcutaneous adipose tissue (L) assessed by magnetic resonance imaging (MRI)
timeFrame: Up to day -20, week 48
measure: Change in abdominal subcutaneous adipose tissue (L) assessed by magnetic resonance imaging (MRI)
timeFrame: Up to day -20, week 72
measure: Change in Body weight (% and kg)
timeFrame: Week 0, week 48
measure: Change in Body weight (% and kg)
timeFrame: Week 0, week 72
measure: Change in Waist circumference
timeFrame: Week 0, week 48
measure: Change in Waist circumference
timeFrame: Week 0, week 72
measure: Change in Body mass index (BMI)
timeFrame: Week 0, week 48
measure: Change in Body mass index (BMI)
timeFrame: Week 0, week 72
measure: Number of treatment-emergent adverse events (TEAEs)
timeFrame: Weeks 0 - 48
measure: Number of treatment-emergent adverse events (TEAEs)
timeFrame: Weeks 0 - 79
measure: Number of treatment-emergent hypoglycaemic episodes
timeFrame: Weeks 0 - 48
measure: Number of treatment-emergent hypoglycaemic episodes
timeFrame: Weeks 0 - 79
Other outcomes:
Locations:
city: Mainz
country: Germany
facility: Novo Nordisk Investigational Site
city: Neuss
country: Germany
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Reporting Anchor and Disclosure (1452)
role: STUDY_DIRECTOR
References:
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.
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.