A Research Study on How Semaglutide Works in People With Fatty Liver Disease and Liver Damage

NCT03987451 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: NN9931-4492U1111-1224-40622018-004484-31
• Study Type: interventional
• Target: 71
• Locations: 5 countries
• Sites: 38

Brief Summary

Semaglutide is a medicine studied in patients with non-alcoholic steatohepatitis (NASH), as it may improve liver damage. Participants will either get semaglutide or placebo (a dummy medicine) - which treatment participants get is decided by chance. The study will last for about 61 weeks in total. Participants will have 10 clinic visits and 3 phone calls with the study doctor or staff during the study. Some of the clinic visits may be spread over more days. Participants will need to inject themselves with medicine under the skin. Participants will have to do this once a week for 48 weeks. The study includes magnetic resonance imaging (MRI) scans of the liver, 1 or 2 liver tissue samples, ultrasound scans of the stomach and a possible examination of the food pipe. For some tests participants may need to remove some items of clothing. Participants will stop in the study if the doctor thinks that there are any risks for their health. The information collected from participants during the study may help them and other patients with NASH in the future. Women cannot take part if pregnant, breast-feeding or planning to become pregnant during the study period.

Conditions

Non-alcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With At Least One Stage of Liver Fibrosis Improvement With No Worsening of Non-Alcoholic Steatohepatitis (NASH) After 48 Weeks

  NASH resolution defined by NASH clinical research network (CRN) as lobular inflammation of 0 or 1; hepatocellular ballooning reduced to 0; both criteria were necessary conditions. Hepatocellular ballooning ranges from 0-2; lobular inflammation ranges from 0-3, higher scores indicating more severe hepatocellular ballooning/lobular inflammation. Worsening of NASH defined by NASH CRN as increase of at least 1 stage of either lobular inflammation, hepatocyte ballooning or steatosis. Worsening of fibrosis defined by increase in fibrosis at least 1 stage of Kleiner fibrosis classification: fibrosis stages range from 0-4, higher scores indicating greater fibrosis (0=None, 4=Cirrhosis). Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

  Week 48

Secondary Outcomes (47)

• Change From Baseline in Liver Fat Content Measured by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF)-Ratio to Baseline

  Baseline (week 0), Week 48

• Change From Baseline in Liver Stiffness Measured by Magnetic Resonance Elastography (MRE)-Ratio to Baseline

  Baseline (week 0), Week 48

• Percentage of Participants With NASH Resolution After 48 Weeks

  Week 48

• Change From Baseline in Fibrosis-4 Score-Ratio to Baseline

  Baseline (week 0), Week 48

• Percentage of Participants With Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS)

  Baseline (week 0), Week 48

Study Arms (2)

Semaglutide

EXPERIMENTAL

Dose escalation to 2.4 mg of semaglutide once-weekly

Drug: Semaglutide

Placebo

PLACEBO COMPARATOR

Semaglutide placebo once-weekly

Drug: Placebo (semaglutide)

Interventions

Semaglutide DRUG

Semaglutide given subcutaneously (s.c., under the skin) once-weekly for 48 weeks

Semaglutide

Placebo (semaglutide) DRUG

Semaglutide placebo s.c. given once-weekly for 48 weeks

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:

• Male or female, aged 18-75 years (both inclusive) at the time of signing informed consent.
• Histologic evidence of NASH and fibrosis stage 4 according to the NASH CRN classification based on central pathologist evaluation of a liver biopsy obtained within 360 days prior to screening. In subjects who have never had a liver biopsy showing NASH and F4, liver stiffness above 14 kPa by FibroScan® at screening must be documented before subjects can have a trial-related liver biopsy
• A histological NAFLD activity score (NAS) equal to or above 3 with a score of 1 or more in lobular inflammation and hepatocyte ballooning based on central pathologist evaluation
• Body mass index equal to or above 27 kg/m\^2

You may not qualify if:

• Presence or history of hepatic decompensation (e.g. ascites, variceal bleeding, hepatic encephalopathy or spontaneous bacterial peritonitis) or liver transplantation
• Presence or history of gastroesophageal varices within the past 360 days prior to screening. For subjects with no known history of gastroesophageal varices and with a Fibroscan® equal to or above 20 kPa and thrombocytes equal to or below 150,000, a esophagogastroduodenoscopy must be performed to evaluate presence of gastroesophageal varices
• Presence or history of hepatocellular carcinoma
• Treatment with vitamin E (at doses equal to or above 800 IU/day) or pioglitazone which has not been at a stable dose in the opinion of the investigator in the period from 90 days prior to screening
• Treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in the period from 90 days prior to screening

Sponsors & Collaborators

• Novo Nordisk A/S: lead

Study Sites (38)

Arizona Liver Health

Chandler, Arizona, 85224, United States

Location

The Institute for Liver Health dba Arizona Liver Health

Peoria, Arizona, 85381, United States

Location

Southern California Research Center

Coronado, California, 92118, United States

Location

Altman Clinical Translational Research Institute

La Jolla, California, 92037, United States

Location

Inland Empire Clinical Trials LLC

Rialto, California, 92377, United States

Location

Excel Medical Center Clinical Trials, LLC

Boca Raton, Florida, 33434, United States

Location

University of Florida-CTRB

Gainesville, Florida, 32610, United States

Location

University of Miami/Schiff Center for Liver Diseases

Miami, Florida, 33136, United States

Location

Piedmont Research Institute

Atlanta, Georgia, 30309, United States

Location

Gastrointestinal Specialists of Georgia

Marietta, Georgia, 30060, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Digestive Research Alliance of Michiana

South Bend, Indiana, 46635, United States

Location

University of Kentucky Hospital

Lexington, Kentucky, 40508, United States

Location

Mercy Medical Center, GI Research

Baltimore, Maryland, 21202, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Gastroenterology Center For The Mid-South

Germantown, Tennessee, 38138, United States

Location

Digestive Health Research - Tristar Summit Medical Center

Hermitage, Tennessee, 37076, United States

Location

Quality Medical Research

Nashville, Tennessee, 37211, United States

Location

Texas Clinical Research Institute, LLC

Arlington, Texas, 76012, United States

Location

The University of Texas Southwestern Medical Center - Dallas

Dallas, Texas, 75390-8887, United States

Location

American Research Corporation at the Texas Liver Institute

San Antonio, Texas, 78215, United States

Location

VCU Health Systems

Richmond, Virginia, 23298, United States

Location

Hôpital Beaujon

Clichy, 92110, France

Location

Hôpital de la Croix Rousse

Lyon, 69317, France

Location

Hôpital Cochin

Paris, 75014, France

Location

Groupe Hospitalier PITIE-SALPETRIERE

Paris, 75651, France

Location

Groupe Hospitalier Mutualiste des Portes du Sud

Vénissieux, 69200, France

Location

Hepatologie Universitätsklinikum Frankfurt/M

Frankfurt, 60590, Germany

Location

Universitätsklinikum Leipzig, Klinik und Poliklinik

Leipzig, 04103, Germany

Location

Universitätsmedizin der Johannes-Gutenberg-Universität Mainz

Mainz, 55131, Germany

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Virgen del Rocío

Seville, 41013, Spain

Location

New Queen Elizabeth Hospital Birmingham

Birmingham, B15 2TH, United Kingdom

Location

Liver Research

London, SE5 9RS, United Kingdom

Location

Freeman Hospital, Newcastle

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Nottingham University Hospital

Nottingham, NG7 2UH, United Kingdom

Location

Related Publications (1)

• Loomba R, Abdelmalek MF, Armstrong MJ, Jara M, Kjaer MS, Krarup N, Lawitz E, Ratziu V, Sanyal AJ, Schattenberg JM, Newsome PN; NN9931-4492 investigators. Semaglutide 2.4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: a randomised, placebo-controlled phase 2 trial. Lancet Gastroenterol Hepatol. 2023 Jun;8(6):511-522. doi: 10.1016/S2468-1253(23)00068-7. Epub 2023 Mar 16.

  PMID: 36934740 BACKGROUND

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Clinical Reporting Office (2834)
• Organization: Novo Nordisk A/S

clinicaltrials@novonordisk.com

(+1) 866-867-7178

Study Officials

• Clinical Reporting Anchor and Disclosure (1452)

  Novo Nordisk A/S

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: June 12, 2019
• First Posted: June 17, 2019
• Study Start: June 18, 2019
• Primary Completion: April 22, 2021
• Study Completion: June 10, 2021
• Last Updated: May 29, 2024
• Results First Posted: May 29, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share

Locations

ES (2); US (24); DE (3); GB (4); FR (5)