A Study to Test Safety and Efficacy of Survodutide (BI456906) in Adults With Non-alcoholic Steatohepatitis (NASH) and Fibrosis (F1-F3)

November 7, 2024 updated by: Boehringer Ingelheim

Multicenter, Double-blind, Parallel-group, Randomized, 48 Weeks, Dose-ranging, Placebo-controlled Phase II Trial to Evaluate Efficacy, Safety and Tolerability of Multiple Subcutaneous (s.c.) Doses of BI 456906 in Patients With Non-alcoholic Steatohepatitis (NASH) and Fibrosis.

This study is open for men and women with a liver disease called nonalcoholic steatohepatitis (NASH) and liver fibrosis. The purpose of the study is to find out whether a medicine called BI 456906 helps patients with NASH and liver fibrosis. The study tests 3 different doses of BI 456906 to find the dose that helps best. Participants are put into 4 groups randomly, which means by chance. There are 3 groups that each receive a different dose of BI 456906 and there is 1 group that receives placebo. BI 456906 and placebo are given as an injection under the skin once per week. The placebo injection looks like the BI 456906 injection but does not contain any medicine.

Participants are in the study for a little over 1 year (60 weeks). During this time, they visit the study site several times and have some video calls in addition. At the visits, the study doctors take different measurements. To see whether the treatment works, the doctors take a very small sample of liver tissue (biopsy) from each participant at the start and at the end of the study. They also examine the liver by ultrasound and MRI. The doctors also regularly check the general health of the participants.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

295

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Queensland
      • Southport, Queensland, Australia, 4215
        • Gold Coast University Hospital
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Monash Medical Centre
      • Parkville, Victoria, Australia, 3050
        • Royal Melbourne Hospital
  • Austria
      • Graz, Austria, 8036
        • Medical University of Graz State Hospital - University Hospital Graz
      • Innsbruck, Austria, A-6020
        • Medical University of Innsbruck
      • Linz, Austria, A-4010
        • Ordensklinikum Linz GmbH - Barmherzige Schwestern
  • Belgium
      • Edegem, Belgium, 2650
        • Edegem - UNIV UZ Antwerpen
  • Canada
    • Ontario
      • London, Ontario, Canada, N6A 5A5
        • University Hospital (LHSC)
      • Toronto, Ontario, Canada, M6H 3M1
        • Toronto Liver Centre
    • Quebec
      • Chicoutimi, Quebec, Canada, G7H 7K9
        • Ecogene-21
  • China
      • Beijing, China, 100044
        • Peking University People's Hospital
      • Beijing, China, 100050
        • Beijing Friendship Hospital
      • Beijing, China, 100015
        • Beijing Ditan Hospital Capital Medical University
      • Beijing, China, 100044
        • Beijing Tsinghua Changgung Hospital
      • Changchun, China, 130021
        • The First Hospital of Jilin University
      • Guangzhou, China, 510515
        • NanFang Hosptial
      • Guangzhou, China, 510080
        • The First Afiliated Hospital, Sun Yet-sen University
      • Hangzhou, China, 310016
        • Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine
      • Kunming, China, 650032
        • First People's hospital of Yunann Province
      • Nanjing, China, 210003
        • The Second Hospital of Nanjing
      • Shanghai, China, 201508
        • Shanghai Public Health Clinical Center
      • Tianjin, China, 300170
        • Tianjin Third Central Hospital
      • Wenxzhou, China, 325000
        • The First Affiliated Hospital of Wenzhou Med College
  • Czechia
      • Liberec, Czechia, 460 63
        • Regional Hospital Liberec
      • Prague, Czechia, 128 08
        • General Faculty Hospital, Prague
  • France
      • Nice, France, 06200
        • HOP l'Archet
      • Paris, France, 75651
        • HOP La Pitié Salpêtrière
      • Pessac, France, 33604
        • HOP Haut-Lévêque
      • Strasbourg, France, 67091
        • HOP Civil
  • Germany
      • Aachen, Germany, 52074
        • Universitätsklinikum Aachen, AöR
      • Berlin, Germany, 12627
        • Synexus Clinical Research GmbH
      • Bochum, Germany, 44892
        • Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH
      • Düsseldorf, Germany, 40225
        • Universitatsklinikum Dusseldorf
      • Frankfurt, Germany, 60313
        • Synexus Clinical Research GmbH
      • Leipzig, Germany, 04103
        • Synexus Clinical Research GmbH
      • Mainz, Germany, 55131
        • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
      • Mannheim, Germany, 68167
        • Universitätsklinikum Mannheim GmbH
      • Ulm, Germany, 89081
        • Universitätsklinikum Ulm
  • Greece
      • Haidari-Athens, Greece, 12462
        • Attikon University Hospital
      • Thessaloniki, Greece, 54642
        • General Hospital of Thessaloniki "Hippokrateio"
  • Hong Kong
      • Hong Kong, Hong Kong, 999077
        • Prince of Wales Hospital
      • Hong Kong, Hong Kong, 999077
        • Queen Mary Hospital
  • Hungary
      • Budapest, Hungary, 1036
        • Synexus Hungary Healthcare Service Ltd.
      • Budapest, Hungary, 1097
        • Fed.St. Istvan&Szent Laszlo Hospital
      • Gyula, Hungary, 5700
        • Synexus Hungary Healthcare Service Ltd
  • Israel
      • Jerusalem, Israel, 9103102
        • Shaare Zedek Medical Center, Jerusalem 91031
      • Nahariya, Israel, 22100
        • Western Galilee Hospital
      • Petach Tikva, Israel, 49100
        • Rabin Medical Center Beilinson
      • Tel Aviv, Israel, 64239
        • Sourasky Medical Center
      • Tel-Hashomer, Israel, 5265601
        • The Chaim Sheba Medical Center
  • Italy
      • Baggiovara (MO), Italy, 41126
        • Ospedale Civile di Baggiovara
      • Palermo, Italy, 90127
        • A.O. Univ. Policlinico "Paolo Giaccone"
      • Roma, Italy, 00195
        • Poli Univ A. Gemelli
      • Rozzano (MI), Italy, 20089
        • Istituto Clinico Humanitas
      • SAN Giovanni Rotondo (FG), Italy, 71013
        • IRCCS Ospedale "Casa Sollievo della Sofferenza"
      • Torino, Italy, 10126
        • AO Città della Salute e Scienza
  • Japan
      • Ehime, Toon, Japan, 791-0295
        • Ehime University Hospital
      • Fukui, Fukui, Japan, 918-8503
        • Fukuiken Saiseikai Hospital
      • Fukuoka, Kurume, Japan, 830-0011
        • Kurume University Hospital
      • Gifu, Ogaki, Japan, 503-8502
        • Ogaki Municipal Hospital
      • Hokkaido, Sapporo, Japan, 062-8618
        • Japan Community Health Care Organization Hokkaido Hospital
      • Kagawa, Kita-gun, Japan, 761-0793
        • Kagawa University Hospital
      • Kagawa, Takamatsu, Japan, 760-8557
        • Kagawa Prefectural Central Hospital
      • Kanagawa, Kawasaki, Japan, 216-8511
        • St. Marianna University Hospital
      • Kanagawa, Sagamihara, Japan, 252-0375
        • Kitasato University Hospital
      • Kanagawa, Yokohama, Japan, 236-0004
        • Yokohama City University Hospital
      • Kanagawa, Yokohama, Japan, 245-8575
        • National Hospital Organization Yokohama Medical Center
      • Kumamoto, Kumamoto, Japan, 860-8556
        • Kumamoto University Hospital
      • Kyoto, Kyoto, Japan, 602-8566
        • University Hospital Kyoto Prefectural University of Medicine
      • Nagano, Matsumoto, Japan, 390-8621
        • Shinshu University Hospital
      • Nagano, Nagano, Japan, 381-8551
        • Nagano Municipal Hospital
      • Nara, Kashihara, Japan, 634-8522
        • Nara Medical University Hospital
      • Osaka, Suita, Japan, 564-0013
        • Suita Hospital
      • Saga, Saga, Japan, 849-8501
        • Saga University Hospital
      • Shizuoka, Hamamatsu, Japan, 431-3192
        • Hamamatsu University Hospital
      • Shizuoka, Izunokuni, Japan, 410-2295
        • Juntendo University Shizuoka Hospital
      • Tokyo, Bunkyo-ku, Japan, 113-8519
        • Tokyo Medical and Dental University Hospital
  • Korea, Republic of
      • Busan, Korea, Republic of, 49241
        • Pusan National Univ. Hosp
      • Daegu, Korea, Republic of, 42601
        • Keimyung University Dongsan Hospital
      • Seoul, Korea, Republic of, 03080
        • Seoul National University Hospital
  • Malaysia
      • Kelantan, Malaysia, 16150
        • universiti Sains Malaysia hospital
      • Kuala Lumpur, Malaysia, 59100
        • University of Malaya Medical Centre
      • Selangor, Malaysia, 68100
        • Hospital Selayang
  • Netherlands
      • Amsterdam, Netherlands, 1105 AZ
        • Amsterdam UMC, location VUmc
      • Leiden, Netherlands, 2333 ZA
        • Leids Universitair Medisch Centrum (LUMC)
      • Rotterdam, Netherlands, 3045 PM
        • Sint Franciscus, Locatie Vlietland
  • New Zealand
      • Auckland, New Zealand, 1010
        • New Zealand Clinical Research (NZCR)
      • Papatoetoe, New Zealand, 2025
        • Middlemore Clinical Trials
  • Poland
      • Bydgoszcz, Poland, 85-605
        • INTERCORE Medical Center
      • Czestochowa, Poland, 42202
        • Synexus Poland, Branch in Czestochowa
      • Elblag, Poland, 82-300
        • Private health care facility "Your Health EL" LLC
      • Gdansk, Poland, 80-382
        • Synexus Polska SCM Sp. z o.o. Gdansku, Gdansk
      • Gdynia, Poland, 81-384
        • Synexus Polska Sp. z o.o. Oddzial w Gdyni, Gdynia
      • Katowice, Poland, 40-752
        • University Clinical Center Professor Gibinskiego
      • Krakow, Poland, 30688
        • University Hospital in Krakow
      • Oswiecim, Poland, 32600
        • Medicome Limited Liability Company
      • Warszawa, Poland, 01-192
        • Centrum Medyczne Synexus
      • Wroclaw, Poland, 50-088
        • Synexus Poland, Branch in Wroclaw
      • Zamosc, Poland, 22400
        • ETG Zamosc
  • Portugal
      • Lisboa, Portugal, 1649-035
        • ULS de Santa Maria, E.P.E
      • Porto, Portugal, 4202-451
        • Centro Hospitalar Universitário São João,EPE
  • Singapore
      • Singapore, Singapore, 119074
        • National University Hospital
      • Singapore, Singapore, 168753
        • Singapore General Hospital
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Vall d'Hebron
      • Majadahonda, Spain, 28222
        • Hospital Puerta de Hierro
      • Pontevedra, Spain, 36071
        • Hospital De Montecelo
      • Santander, Spain, 39008
        • Hospital Universitario Marqués de Valdecilla
      • Sevilla, Spain, 41013
        • Hospital Virgen del Rocío
      • Valencia, Spain, 46014
        • Hospital General Universitario de Valencia
  • Taiwan
      • ChiaYi, Taiwan, 60002
        • Chia Yi Christian Hospital
      • Kaohsiung, Taiwan, 807
        • Kaohsiung Medical University Chung-Ho Memorial Hospital
      • Tainan, Taiwan, 704
        • National Chen Kung University, Dept of Neurology
      • Taoyuan County, Taiwan, 333
        • Chang Gung Memorial Hospital(Linkou)
  • United Kingdom
      • Birmingham, United Kingdom, B15 2TH
        • Queen Elizabeth Hospital
      • Hexham, United Kingdom, NE46 1QJ
        • Synexus - Hexham
      • Liverpool, United Kingdom, L9 7AL
        • Aintree University Hospital
      • London, United Kingdom, SE5 9RS
        • King's College Hospital
      • Nottingham, United Kingdom, NG7 2RD
        • Queen's Medical Centre
  • United States
    • Alabama
      • Huntsville, Alabama, United States, 35801
        • North Alabama Health Research, LLC
    • California
      • Coronado, California, United States, 92118
        • Southern California Research Center
      • Huntington Park, California, United States, 90255
        • Velocity Clinical Research
      • Panorama City, California, United States, 91402
        • Velocity Clinical Research
      • San Francisco, California, United States, 94115
        • Quest Clinical Research
    • Colorado
      • Colorado Springs, Colorado, United States, 80907
        • Peak Gastroenterology Associates
    • Florida
      • Doral, Florida, United States, 33166
        • Integrity Clinical Research, LLC
      • Fort Myers, Florida, United States, 33912
        • Covenant Metabolic Specialists, LLC
      • Miami, Florida, United States, 33135
        • Optimus U Corporation
      • Miami, Florida, United States, 33157
        • Sanchez Clinical Research ,Inc
      • Ocala, Florida, United States, 34471
        • Ocala GI Research
      • Orlando, Florida, United States, 32808
        • Omega Research Orlando, LLC
      • Sarasota, Florida, United States, 34240
        • Covenant Metabolic Specialists, LLC
    • Georgia
      • Marietta, Georgia, United States, 30060
        • Gastrointestinal Specialists of Georgia
    • Indiana
      • South Bend, Indiana, United States, 46635
        • Digestive Research Alliance of Michiana
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals and Clinics
    • Louisiana
      • Bastrop, Louisiana, United States, 71220
        • Delta Research Partners, LLC
      • Lake Charles, Louisiana, United States, 70601
        • Centex Studies, Inc.
      • Marrero, Louisiana, United States, 70072
        • Tandem Clinical Research
    • Massachusetts
      • Fall River, Massachusetts, United States, 02721
        • NECCR Primacare Research, LLC
    • Mississippi
      • Biloxi, Mississippi, United States, 39532
        • National Diabetes and Obesity Research Institute
      • Flowood, Mississippi, United States, 39232
        • Gastrointestinal Associates
    • New Jersey
      • Florham Park, New Jersey, United States, 07932
        • AIG Digestive Disease Research
    • North Carolina
      • Concord, North Carolina, United States, 28027
        • Northeast GI Research Division
      • Morehead City, North Carolina, United States, 28557
        • Lucas Research, Inc.
    • South Carolina
      • Greenwood, South Carolina, United States, 29646
        • Digestive Diseases Research Center
      • Summerville, South Carolina, United States, 29485
        • Palmetto Clinical Research
    • Tennessee
      • Hermitage, Tennessee, United States, 37076
        • Digestive Health Research, LLC
    • Texas
      • Arlington, Texas, United States, 76012
        • Texas Clinical Research Institute, LLC
      • Austin, Texas, United States, 78757
        • Texas Liver Institute
      • Brownsville, Texas, United States, 78520
        • South Texas Research Institute
      • Edinburg, Texas, United States, 78539
        • South Texas Research Institute
      • Houston, Texas, United States, 77030
        • Houston Methodist Hospital
      • San Antonio, Texas, United States, 78229
        • Pinnacle Clinical Research
      • San Antonio, Texas, United States, 78215
        • American Research Corporation at The Texas Liver Institute
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Male or female patients ≥ 18 years (or who are of legal age in countries where that is greater than 18 years) and ≤ 80 years of age at time of consent.
  2. Diagnosis of non-alcoholic steatohepatitis (NASH) (Non-alcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) ≥ 4, with at least 1 point in inflammation and ballooning each) and fibrosis stage F1-F3 proven by a biopsy conducted during the screening period or by a historical biopsy conducted within the last 6 months prior to randomization and stable body weight defined as less than 5% self-reported change in body weight between the historical biopsy and randomization, if a historical biopsy is used.
  3. Liver fat fraction ≥ 8% measured by Magnetic Resonance Imaging (MRI)-Proton Density Fat Fraction (PDFF) and liver stiffness > 6.0 kPa measured by FibroScan® at Visit 1 (if biopsy is scheduled during the screening period MRI-PDFF and FibroScan® assessments have to be performed prior to the biopsy). However, the diagnosis of NASH and fibrosis at liver biopsy (including historical biopsy) is the primary assessment to establish patient eligibility.
  4. Patients willing and able to undergo liver biopsies per protocol as judged by the Investigator.
  5. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.
  6. Women of childbearing potential (WOCBP)1 must be willing and able to use two forms of effective contraception where at least one form is highly effective methods of birth control per International Council on Harmonisation (ICH) M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information.

Further inclusion criteria apply.

Exclusion Criteria:

  1. Current or history of significant alcohol consumption (defined as intake of > 210 g/ week in males and > 140 g/ week in females on average over a consecutive period of more than 3 months) or inability to reliably quantify alcohol consumption based on Investigator judgement within the last 5 years.
  2. Intake of medications historically associated with liver injury, hepatic steatosis or steatohepatitis within 12 weeks prior to Visit 1. Intake of restricted medications or any medications considered likely to interfere with the safe conduct of the trial.
  3. History of other forms of chronic liver disease (e.g., viral hepatitis, autoimmune liver disease, primary biliary sclerosis, primary sclerosing cholangitis, Wilson's disease, hemochromatosis, Alpha-1 Antitrypsin (A1At) deficiency, history of liver transplantation). Hepatitis B and C testing will be done at Visit 1. Patients with positive Hepatitis B surface antigen (HBsAg) should be excluded. Patients treated for hepatitis C must have a negative RNA test at screening and also be Hepatitis C Virus (HCV) RNA negative for at least 3 years prior to screening in order to be eligible for the trial.
  4. Suspicion, diagnosis, or history of hepatocellular carcinoma (HCC), or any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix.
  5. Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, manifest hypo- or hyperthyroidism at Visit 1.
  6. History of chronic or acute pancreatitis or elevation of serum lipase/amylase > 2x ULN or fasting serum triglyceride levels of > 500 mg/dL (> 5.65 mmol/L) at screening.
  7. Known history of HIV (Human Immunodeficiency Virus) infection and/or tuberculosis and/or an acute COVID-19 infection at Visit 1 (confirmed by SARS CoV-2 RT-PCR test). Further exclusion criteria apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Survodutide 2.4 mg - planned maintenance treatment
Drug: Survodutide
Survodutide
Other Names:
  • BI 456906
Experimental: Survodutide 4.8 mg - planned maintenance treatment
Drug: Survodutide
Survodutide
Other Names:
  • BI 456906
Experimental: Survodutide 6.0 mg - planned maintenance treatment
Drug: Survodutide
Survodutide
Other Names:
  • BI 456906
Placebo Comparator: Placebo - planned maintenance treatment
Drug: Placebo
Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Improvement (Yes/ no) From Baseline in Liver Histological Findings Based on Liver Biopsy After 48 Weeks of Treatment in Patients With NASH (NAS ≥ 4, Fibrosis F1-F3) - Actual Maintenance Treatment
Time Frame: At baseline and at 48 weeks.

Percentage of patients who had an improvement from baseline in liver histological findings based on liver biopsy after 48 weeks of treatment is reported. Percentages were rounded to one decimal place.

Improvement in histological findings was defined as a composite of improvement in NASH and no worsening of fibrosis.

Improvement in non-alcoholic steatohepatitis (NASH) was defined as decrease of at least 2 points in non-alcoholic fatty liver disease (NAFLD) activity score (NAS) with at least 1 point decrease in NAS subscore of either lobular inflammation or ballooning.

The NAS represents the sum of subscores for steatosis (scored from 0-3), lobular inflammation (scored from 0-3) and ballooning (scored from 0-2), and the total score ranges from 0 to 8 with higher scores representing worsening of the disease.

The total score for the fibrosis stage ranges from 0 to 4 with higher score indication worsening of the disease.

Patients without post-baseline data were considered non-responders.
At baseline and at 48 weeks.
Improvement (Yes/ no) From Baseline in Liver Histological Findings Based on Liver Biopsy After 48 Weeks of Treatment in Patients With NASH (NAS ≥ 4, Fibrosis F1-F3) - Planned Maintenance Treatment
Time Frame: At baseline and after 48 weeks of treatment.

Percentage of patients who had an improvement from baseline in liver histological findings based on liver biopsy after 48 weeks of treatment is reported. Percentages were rounded to one decimal place.

Improvement in histological findings was defined as a composite of improvement in non-alcoholic steatohepatitis (NASH) and no worsening of fibrosis.

Improvement in NASH was defined as decrease of at least 2 points in non-alcoholic fatty liver disease (NAFLD) activity score (NAS) with at least 1 point decrease in NAS subscore of either lobular inflammation or ballooning.

The NAS represents the sum of subscores for steatosis (scored from 0-3), lobular inflammation (scored from 0-3) and ballooning (scored from 0-2), and the total score ranges from 0 to 8 with higher scores representing worsening of the disease.

The total score for the fibrosis stage ranges from 0 to 4 with higher score indication worsening of the disease.

Patients without post-baseline data were considered non-responders.
At baseline and after 48 weeks of treatment.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Improvement of Liver Fat Content (Yes/ no) Defined as at Least 30% Relative Reduction in Liver Fat Content After 48 Weeks of Treatment Compared to Baseline Assessed by MRI-PDFF - Actual Maintenance Treatment
Time Frame: At baseline and after 48 weeks.

Percentage of participants with improvement in liver fat content is reported. Improvement in liver fat content was defined as percentage reduction from baseline of ≥30% in liver fat content after 48 weeks of treatment compared to baseline. Percentages were rounded to one decimal place.

Liver fat content was assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF).

Patients without post-baseline values were imputed as non-responders.
At baseline and after 48 weeks.
Improvement of Liver Fat Content (Yes/ no) Defined as at Least 30% Relative Reduction in Liver Fat Content After 48 Weeks of Treatment Compared to Baseline Assessed by MRI-PDFF - Planned Maintenance Treatment
Time Frame: At baseline and at 48 weeks.

Percentage of participants with improvement in liver fat content is reported. Improvement in liver fat content was defined as percentage reduction from baseline of ≥30% in liver fat content after 48 weeks of treatment compared to baseline.

Liver fat content was assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF).

Patients without post-baseline values were imputed as non-responders.
At baseline and at 48 weeks.
Absolute Change of Liver Fat Content From Baseline After 48 Weeks of Treatment Assessed by MRI-PDFF - Actual Maintenance Treatment
Time Frame: MMRM included measurements from baseline and at Week 28 and at Week 48 after first drug administration. MMRM estimates of absolute change from baseline to Week 48 is reported.

Absolute change of liver fat content (percentage [%]) from baseline after 48 weeks of treatment is reported. Liver fat content was assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF).

Least Squares Mean (Standard error) were calculated from mixed-effect model for repeated measures (MMRM) including fixed effects for baseline liver fat content (%) as a continuous linear covariate, and treatment, presence of diabetes of any type [yes, no], baseline fibrosis score [F1, F2, F3], visit, treatment by visit interaction and baseline by visit interaction as factors.
MMRM included measurements from baseline and at Week 28 and at Week 48 after first drug administration. MMRM estimates of absolute change from baseline to Week 48 is reported.
Absolute Change of Liver Fat Content From Baseline After 48 Weeks of Treatment Assessed by MRI-PDFF - Planned Maintenance Treatment
Time Frame: MMRM included measurements from baseline and at Week 28 and at Week 48 after first drug administration. MMRM estimates of absolute change from baseline to Week 48 is reported.

Absolute change of liver fat content from baseline after 48 weeks of treatment is reported. Liver fat content was assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF).

Least Squares Mean (Standard error) were calculated from mixed-effect model for repeated measures (MMRM) including fixed effects for baseline liver fat content (%) as a continuous linear covariate, and treatment, presence of diabetes of any type [yes, no], baseline fibrosis score [F1, F2, F3], visit, treatment by visit interaction and baseline by visit interaction as factors.
MMRM included measurements from baseline and at Week 28 and at Week 48 after first drug administration. MMRM estimates of absolute change from baseline to Week 48 is reported.
Percent Change of Liver Fat Content From Baseline After 48 Weeks of Treatment Assessed by MRI-PDFF - Actual Maintenance Treatment
Time Frame: MMRM included measurements from baseline and at Week 28 and at Week 48 after first drug administration. MMRM estimates of percent change from baseline to Week 48 is reported.

Percent change of liver fat content (percentage [%]) from baseline after 48 weeks of treatment is reported. Liver fat content was assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF).

Least Squares Mean (Standard error) were calculated from mixed-effect model for repeated measures (MMRM) including fixed effects for baseline liver fat content (%) as a continuous linear covariate, and treatment, presence of diabetes of any type [yes, no], baseline fibrosis score [F1, F2, F3], visit, treatment by visit interaction and baseline by visit interaction as factors.
MMRM included measurements from baseline and at Week 28 and at Week 48 after first drug administration. MMRM estimates of percent change from baseline to Week 48 is reported.
Percent Change of Liver Fat Content From Baseline After 48 Weeks of Treatment Assessed by MRI-PDFF - Planned Maintenance Treatment
Time Frame: MMRM included measurements from baseline and at Week 28 and at Week 48 after first drug administration. MMRM estimates of percent change from baseline to Week 48 is reported.

Percent change of liver fat content (percentage [%]) from baseline after 48 weeks of treatment is reported. Liver fat content was assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF).

Least Squares Mean (Standard error) were calculated from mixed-effect model for repeated measures (MMRM) including fixed effects for baseline liver fat content (%) as a continuous linear covariate, and treatment, presence of diabetes of any type [yes, no], baseline fibrosis score [F1, F2, F3], visit, treatment by visit interaction and baseline by visit interaction as factors.
MMRM included measurements from baseline and at Week 28 and at Week 48 after first drug administration. MMRM estimates of percent change from baseline to Week 48 is reported.
Improvement of Fibrosis (Yes/ no) Defined as at Least One Stage Decrease in Fibrosis Stage After 48 Weeks of Treatment Assessed by Liver Biopsy - Actual Maintenance Treatment
Time Frame: At baseline and after 48 weeks of treatment.

Percentage of participants with improvement of liver fibrosis is reported. Improvement of fibrosis was defined as at least one stage decrease in fibrosis stage after 48 weeks of treatment assessed by liver biopsy.

The total score for the fibrosis stage ranges from 0 to 4 with higher score indication worsening of the disease and the stages of fibrosis based on their location are the following:

  • 1A Zone 3, perisinusoidal, delicate;
  • 1B Zone 3, perisinusoidal, dense;
  • 1C Portal, periportal only;
  • 2 Zone 3, perisinusoidal + portal, periportal only;
  • 3 Bridging fibrosis;
  • 4 Cirrhosis. For analysis purposes no distinction was made between stages 1A, 1B and 1C.
At baseline and after 48 weeks of treatment.
Improvement of Fibrosis (Yes/ no) Defined as at Least One Stage Decrease in Fibrosis Stage After 48 Weeks of Treatment Assessed by Liver Biopsy - Planned Maintenance Treatment
Time Frame: At baseline and after 48 weeks of treatment.

Percentage of participants with improvement of liver fibrosis is reported. Improvement of fibrosis was defined as at least one stage decrease in fibrosis stage after 48 weeks of treatment assessed by liver biopsy.

The total score for the fibrosis stage ranges from 0 to 4 with higher score indication worsening of the disease and the stages of fibrosis based on their location are the following:

  • 1A Zone 3, perisinusoidal, delicate;
  • 1B Zone 3, perisinusoidal, dense;
  • 1C Portal, periportal only;
  • 2 Zone 3, perisinusoidal + portal, periportal only;
  • 3 Bridging fibrosis;
  • 4 Cirrhosis. For analysis purposes no distinction was made between stages 1A, 1B and 1C.
At baseline and after 48 weeks of treatment.
Absolute Change From Baseline in NAS After 48 Weeks of Treatment Assessed by Liver Biopsy - Actual Maintenance Treatment
Time Frame: At baseline and 48 weeks of treatment.

Absolute change from baseline in NAS after 48 weeks of treatment assessed by liver biopsy is reported.

The non-alcoholic fatty liver disease (NAFLD) activity score (NAS) represents the sum of subscores for steatosis (scored from 0-3), lobular inflammation (scored from 0-3) and ballooning (scored from 0-2), and the total score ranges from 0 to 8 with higher scores representing worsening of the disease.
At baseline and 48 weeks of treatment.
Absolute Change From Baseline in NAS After 48 Weeks of Treatment Assessed by Liver Biopsy - Planned Maintenance Treatment
Time Frame: At baseline and 48 weeks of treatment.

Absolute change from baseline in NAS after 48 weeks of treatment assessed by liver biopsy is reported.

The non-alcoholic fatty liver disease (NAFLD) activity score (NAS) represents the sum of subscores for steatosis (scored from 0-3), lobular inflammation (scored from 0-3) and ballooning (scored from 0-2), and the total score ranges from 0 to 8 with higher scores representing worsening of the disease.
At baseline and 48 weeks of treatment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boehringer Ingelheim

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 27, 2021

Primary Completion (Actual)

November 9, 2023

Study Completion (Actual)

December 21, 2023

Study Registration Dates

First Submitted

February 24, 2021

First Submitted That Met QC Criteria

February 24, 2021

First Posted (Actual)

February 25, 2021

Study Record Updates

Last Update Posted (Actual)

December 3, 2024

Last Update Submitted That Met QC Criteria

November 7, 2024

Last Verified

November 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1404-0043
  • 2020-002723-11 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement".

Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

The data shared are the raw clinical study data sets.

IPD Sharing Time Frame

After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.

IPD Sharing Access Criteria

For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Non-alcoholic Steatohepatitis (NASH)

Clinical Trials on Placebo

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Slovenia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe