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

NCT03357380 | Completed Phase 1 FDA Drug

• 3 other identifiers: NN9931-43812017-001193-42U1111-1194-3900
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 2

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.

Conditions

Hepatobiliary Disorders; Non-alcoholic Fatty Liver Disease

Outcome Measures

Primary Outcomes (1)

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

  Measured in KPa

  Up to day -20, week 48

Secondary Outcomes (30)

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

  Up to day -20, week 24

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

  Up to day -20, week 72

• Change in relative liver fat content (%) assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF)

  Up to day -20, week 24

• Change in relative liver fat content (%) assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF)

  Up to day -20, week 48

• Change in relative liver fat content (%) assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF)

  Up to day -20, week 72

Study Arms (2)

Semaglutide

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Semaglutide DRUG

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.

Semaglutide

Placebo DRUG

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

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Novo Nordisk A/S: lead

Study Sites (2)

Novo Nordisk Investigational Site

Mainz, 55116, Germany

Location

Novo Nordisk Investigational Site

Neuss, 41460, Germany

Location

Related Publications (2)

• 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.

  PMID: 34570916 RESULT

• 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.

  PMID: 33006125 DERIVED

MeSH Terms

Conditions

Digestive System Diseases; Non-alcoholic Fatty Liver Disease

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases

Study Officials

• Clinical Reporting Anchor and Disclosure (1452)

  Novo Nordisk A/S

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Sponsor staff involved in the clinical trial is masked according to company standard procedures
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2017
• First Posted: November 29, 2017
• Study Start: November 28, 2017
• Primary Completion: March 20, 2020
• Study Completion: March 20, 2020
• Last Updated: November 22, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will share

Locations

DE (2)