Combined Active Treatment in Type 2 Diabetes with NASH

NCT04639414 | Active Not Recruiting Phase 4 DMC

• 2 other identifiers: Combat_T2_NASH_0022019-001987-31
• Study Type: interventional
• Target: 192
• Locations: 2 countries
• Sites: 26

Brief Summary

The aim of this multicentre, prospective, placebo-controlled, double-blind, randomized, 3-arm parallel group, interventional study is to assess for the first time the effects of either a combined therapy with the antihyperglycemic drugs semaglutide and empagliflozin or empagliflozin monotherapy compared to placebo as potential treatments for non-alcoholic steatohepatitis (NASH) in patients with type 2 diabetes.

Conditions

Type 2 Diabetes; Non-alcoholic Steatohepatitis (NASH); Non-alcoholic Fatty Liver Disease (NAFLD)

Keywords

Type 2 Diabetes; Non-alcoholic Steatohepatitis (NASH); Non-alcoholic Fatty Liver Disease (NAFLD); Fatty liver; Diabetes mellitus; Empagliflozin; Semaglutide

Outcome Measures

Primary Outcomes (1)

• Histological resolution of NASH without worsening of fibrosis

  NAFLD status will be assessed by histologic evaluation of liver biopsy samples based on NAFLD activity score. NASH resolution is defined by disappearance of ballooning (score 0), together with either disappearance of lobular inflammation or the persistence of mild lobular inflammation only (score 0 or 1) and resulting in an overall pathologic diagnosis of either steatosis alone or steatosis with mild inflammation; with no worsening of fibrosis. Worsening of fibrosis is defined by an increase of at least one stage of the Kleiner fibrosis classification.

  from baseline to 48 weeks

Secondary Outcomes (4)

• Overall NAFLD activity score (NAS)

  from baseline to 48 weeks

• Stage of fibrosis according to the Kleiner Fibrosis Classification

  from baseline to 48 weeks

• Activity component of NASH according to the steatosis-activity-fibrosis (SAF) score

  from baseline to 48 weeks

• Hepatic steatosis grade

  from baseline to 48 weeks

Study Arms (3)

Combined treatment with Empagliflozin and Semaglutide

EXPERIMENTAL

Combined treatment with Empagliflozin, film-coated tablet, 10mg once daily and Semaglutide, colourless solution in pre-filled pen, 1mg once weekly

Drug: Empagliflozin 10mg oral tablet / Semaglutide 1mg pen injector

Empagliflozin monotherapy

EXPERIMENTAL

Empagliflozin, film-coated tablet, 10mg once daily and Placebo matching Semaglutide (colourless solution in pre-filled pen, once weekly)

Drug: Empagliflozin 10mg oral tablet and placebo pen injector matching semaglutide

Placebo

PLACEBO COMPARATOR

Placebo matching Empagliflozin (film-coated tablet, once daily) and Placebo matching Semaglutide (colourless solution in pre-filled pen, once weekly)

Drug: Placebo matching empagliflozin and placebo pen injector matching semaglutide

Interventions

Empagliflozin 10mg oral tablet / Semaglutide 1mg pen injector DRUG

Measurement of the effect of the combined treatment with semaglutide 1mg/week and empagliflozin 10 mg/d compared to matching placebo after 48-week treatment.

Also known as: Jardiance(R), Ozempic(R)

Combined treatment with Empagliflozin and Semaglutide

Empagliflozin 10mg oral tablet and placebo pen injector matching semaglutide DRUG

Measurement of the effect of empagliflozin monotherapy 10mg/d compared to matching placebo after 48-week treatment.

Also known as: Jardiance(R)

Empagliflozin monotherapy

Placebo matching empagliflozin and placebo pen injector matching semaglutide DRUG

Measurement of the effect of the combined treatment with semaglutide 1mg/week and empagliflozin 10 mg/d OR empagliflozin monotherapy 10mg/d compared to matching placebo after 48-week treatment.

Also known as: Control / Placebo

Placebo

Eligibility Criteria

• Age: 25 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of T2D and NASH with fibrosis stage F1-F3
• Age between 25 and 75 years
• HbA1c ≤ 9.5%
• obtained written informed consent

You may not qualify if:

• Contraindications on liver biopsy
• Evidence of cirrhosis on liver biopsy
• Liver disease of other etiology including chronic viral hepatitis (B or C), alcohol abuse, hemochromatosis, alpha-1 antitrypsin deficiency, autoimmune hepatitis, Wilson's disease, primary sclerosing cholangitis or primary biliary cirrhosis, or liver cirrhosis of any etiology
• History of ketoacidosis
• Alcohol consumption \>30 g/d for males and \>20 g/d for females
• Past (≥5 years) or current history of alcohol or drug abuse and/or psychiatric disease including severe depression necessitating pharmacological treatment
• Medications that may induce steatosis:tamoxifen, raloxifene, oral glucocorticoids or chloroquine
• Planned pregnancy, pregnant or lactating women, positive pregnancy test, and woman of childbearing potential not using two adequate methods of contraception, including a barrier method and a highly efficacious non-barrier method

Sponsors & Collaborators

• German Diabetes Center: lead
• Boehringer Ingelheim: collaborator
• German Center for Diabetes Research: collaborator
• Federal Ministry of Health, Germany: collaborator
• Ministry of Innovation, Science and Research in North Rhine-Westphalia: collaborator
• Novo Nordisk A/S: collaborator

Study Sites (26)

Medizinische Universität Graz

Graz, 8010, Austria

Location

Medizinische Universität Innsbruck

Innsbruck, Austria

Location

Wiener Gesundheitsverbund, Klinik Landstraße

Vienna, 1030, Austria

Location

Medizinische Universität Wien

Vienna, Austria

Location

Wiener Gesundheitsverbund, Klinik Hietzing

Vienna, Austria

Location

German Diabetes Center

Düsseldorf, North Rhine-Westphalia, 40225, Germany

Location

Herz- und Diabeteszentrum NRW

Bad Oeynhausen, 32545, Germany

Location

Franziskus-Krankenhaus Berlin

Berlin, 10787, Germany

Location

Leber- und Studienzentrum Checkpoint

Berlin, 10961, Germany

Location

University Clinics Berlin Charité

Berlin, 12200, Germany

Location

University Clinics Berlin Charité

Berlin, 13353, Germany

Location

University Clinics Bochum

Bochum, 44892, Germany

Location

Städtisches Klinikum Brandenburg GmbH

Brandenburg, 14770, Germany

Location

Städtisches Klinikum Braunschweig gGmbH

Braunschweig, 38126, Germany

Location

University Clinics Carl Gustav Carus Dresden

Dresden, 01307, Germany

Location

Universitätsklinikum Düsseldorf

Düsseldorf, 40225, Germany

Location

University Clinics Essen

Essen, 45147, Germany

Location

University Clinics Frankfurt

Frankfurt, 60590, Germany

Location

University Clinics Freiburg

Freiburg im Breisgau, 79106, Germany

Location

University Clinics Heidelberg

Heidelberg, 69120, Germany

Location

Eugastro GmbH

Leipzig, 04103, Germany

Location

University Clinics Johannes-Gutenberg Mainz

Mainz, 55131, Germany

Location

TUM

München, 81675, Germany

Location

University Clinics Tübingen

Tübingen, 72076, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

University Clinics Würzburg

Würzburg, 97080, Germany

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Non-alcoholic Fatty Liver Disease; Fatty Liver; Diabetes Mellitus

Interventions

empagliflozin; Tablets; semaglutide

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Officials

• Michael Roden, Prof., MD

  German Diabetes Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double-blind placebo-controlled
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2019
• First Posted: November 20, 2020
• Study Start: March 26, 2021
• Primary Completion: January 31, 2025
• Study Completion: December 1, 2025
• Last Updated: October 10, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

AU (5); DE (21)