A Study to Test Safety and Efficacy of Survodutide (BI456906) in Adults With Non-alcoholic Steatohepatitis (NASH) and Fibrosis (F1-F3)
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.
2 other identifiers
interventional
295
24 countries
151
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Apr 2021
151 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 24, 2021
CompletedFirst Posted
Study publicly available on registry
February 25, 2021
CompletedStudy Start
First participant enrolled
April 27, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 9, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
December 21, 2023
CompletedResults Posted
Study results publicly available
December 3, 2024
CompletedDecember 3, 2024
November 1, 2024
2.5 years
February 24, 2021
November 7, 2024
November 7, 2024
Conditions
Outcome Measures
Primary Outcomes (2)
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
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
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 Outcomes (10)
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
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
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
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
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
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.
- +5 more secondary outcomes
Study Arms (4)
Survodutide 2.4 mg - planned maintenance treatment
EXPERIMENTALSurvodutide 4.8 mg - planned maintenance treatment
EXPERIMENTALSurvodutide 6.0 mg - planned maintenance treatment
EXPERIMENTALPlacebo - planned maintenance treatment
PLACEBO COMPARATORInterventions
Survodutide
Eligibility Criteria
You may qualify if:
- 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.
- 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.
- 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.
- Patients willing and able to undergo liver biopsies per protocol as judged by the Investigator.
- Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.
- 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.
You may not qualify if:
- 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.
- 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.
- 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.
- 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.
- Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, manifest hypo- or hyperthyroidism at Visit 1.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (154)
North Alabama Health Research, LLC
Huntsville, Alabama, 35801, United States
Southern California Research Center
Coronado, California, 92118, United States
Velocity Clinical Research
Huntington Park, California, 90255, United States
Velocity Clinical Research
Panorama City, California, 91402, United States
Quest Clinical Research
San Francisco, California, 94115, United States
Peak Gastroenterology Associates
Colorado Springs, Colorado, 80907, United States
Integrity Clinical Research, LLC
Doral, Florida, 33166, United States
Covenant Metabolic Specialists, LLC
Fort Myers, Florida, 33912, United States
Optimus U Corporation
Miami, Florida, 33135, United States
Sanchez Clinical Research ,Inc
Miami, Florida, 33157, United States
Ocala GI Research
Ocala, Florida, 34471, United States
Omega Research Orlando, LLC
Orlando, Florida, 32808, United States
Covenant Metabolic Specialists, LLC
Sarasota, Florida, 34240, United States
Gastrointestinal Specialists of Georgia
Marietta, Georgia, 30060, United States
Digestive Research Alliance of Michiana
South Bend, Indiana, 46635, United States
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242, United States
Delta Research Partners, LLC
Bastrop, Louisiana, 71220, United States
Centex Studies, Inc.
Lake Charles, Louisiana, 70601, United States
Tandem Clinical Research
Marrero, Louisiana, 70072, United States
NECCR PrimaCare Research, LLC
Fall River, Massachusetts, 02721, United States
National Diabetes and Obesity Research Institute
Biloxi, Mississippi, 39532, United States
Gastrointestinal Associates
Flowood, Mississippi, 39232, United States
AIG Digestive Disease Research
Florham Park, New Jersey, 07932, United States
Northeast GI Research Division
Concord, North Carolina, 28027, United States
Lucas Research, Inc.
Morehead City, North Carolina, 28557, United States
Digestive Diseases Research Center
Greenwood, South Carolina, 29646, United States
Palmetto Clinical Research
Summerville, South Carolina, 29485, United States
Digestive Health Research, LLC
Hermitage, Tennessee, 37076, United States
Texas Clinical Research Institute, LLC
Arlington, Texas, 76012, United States
Texas Liver Institute
Austin, Texas, 78757, United States
South Texas Research Institute
Brownsville, Texas, 78520, United States
South Texas Research Institute
Edinburg, Texas, 78539, United States
Houston Methodist Hospital
Houston, Texas, 77030, United States
American Research Corporation at the Texas Liver Institute
San Antonio, Texas, 78215, United States
Pinnacle Clinical Research
San Antonio, Texas, 78229, United States
Virginia Commonwealth University
Richmond, Virginia, 23298, United States
Gold Coast University Hospital
Southport, Queensland, 4215, Australia
Monash Medical Centre
Clayton, Victoria, 3168, Australia
Royal Melbourne Hospital
Parkville, Victoria, 3050, Australia
Medical University of Graz State Hospital - University Hospital Graz
Graz, 8036, Austria
Medical University of Innsbruck
Innsbruck, A-6020, Austria
Ordensklinikum Linz GmbH - Barmherzige Schwestern
Linz, A-4010, Austria
Edegem - UNIV UZ Antwerpen
Edegem, 2650, Belgium
University Hospital (LHSC)
London, Ontario, N6A 5A5, Canada
Toronto Liver Centre
Toronto, Ontario, M6H 3M1, Canada
Ecogene-21
Chicoutimi, Quebec, G7H 7K9, Canada
Beijing Ditan Hospital Capital Medical University
Beijing, 100015, China
Beijing Tsinghua Changgung Hospital
Beijing, 100044, China
Peking University People's Hospital
Beijing, 100044, China
Beijing Friendship Hospital
Beijing, 100050, China
The First Hospital of Jilin University
Changchun, 130021, China
The First Afiliated Hospital, Sun Yet-sen University
Guangzhou, 510080, China
NanFang Hosptial
Guangzhou, 510515, China
Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine
Hangzhou, 310016, China
First People's hospital of Yunann Province
Kunming, 650032, China
The Second Hospital of Nanjing
Nanjing, 210003, China
Shanghai Public Health Clinical Center
Shanghai, 201508, China
Tianjin Third Central Hospital
Tianjin, 300170, China
The First Affiliated Hospital of Wenzhou Med College
Wenxzhou, 325000, China
Regional Hospital Liberec
Liberec, 460 63, Czechia
General Faculty Hospital, Prague
Prague, 128 08, Czechia
HOP l'Archet
Nice, 06200, France
HOP La Pitié Salpêtrière
Paris, 75651, France
HOP Haut-Lévêque
Pessac, 33604, France
HOP Civil
Strasbourg, 67091, France
Universitätsklinikum Aachen, AöR
Aachen, 52074, Germany
Synexus Clinical Research GmbH
Berlin, 12627, Germany
Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH
Bochum, 44892, Germany
Universitätsklinikum Düsseldorf
Düsseldorf, 40225, Germany
Synexus Clinical Research GmbH
Frankfurt, 60313, Germany
Synexus Clinical Research GmbH
Leipzig, 04103, Germany
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Mainz, 55131, Germany
Universitätsklinikum Mannheim GmbH
Mannheim, 68167, Germany
Universitätsklinikum Ulm
Ulm, 89081, Germany
Attikon University Hospital
Haidari-Athens, 12462, Greece
General Hospital of Thessaloniki "Hippokrateio"
Thessaloniki, 54642, Greece
Prince of Wales Hospital
Hong Kong, 999077, Hong Kong
Queen Mary Hospital
Hong Kong, 999077, Hong Kong
Synexus Hungary Healthcare Service Ltd.
Budapest, 1036, Hungary
Fed.St. Istvan&Szent Laszlo Hospital
Budapest, 1097, Hungary
Synexus Hungary Healthcare Service Ltd
Gyula, 5700, Hungary
Shaare Zedek Medical Center, Jerusalem 91031
Jerusalem, 9103102, Israel
Western Galilee Hospital
Nahariya, 22100, Israel
Rabin Medical Center Beilinson
Petah Tikva, 49100, Israel
Sourasky Medical Center
Tel Aviv, 64239, Israel
The Chaim Sheba Medical Center
Tel Litwinsky, 5265601, Israel
Ospedale Civile di Baggiovara
Baggiovara (MO), 41126, Italy
A.O. Univ. Policlinico "Paolo Giaccone"
Palermo, 90127, Italy
Poli Univ A. Gemelli
Roma, 00195, Italy
Istituto Clinico Humanitas
Rozzano (MI), 20089, Italy
IRCCS Ospedale "Casa Sollievo della Sofferenza"
SAN Giovanni Rotondo (FG), 71013, Italy
AO Città della Salute e Scienza
Torino, 10126, Italy
Ehime University Hospital
Ehime, Toon, 791-0295, Japan
Fukuiken Saiseikai Hospital
Fukui, Fukui, 918-8503, Japan
Kurume University Hospital
Fukuoka, Kurume, 830-0011, Japan
Ogaki Municipal Hospital
Gifu, Ogaki, 503-8502, Japan
Japan Community Health Care Organization Hokkaido Hospital
Hokkaido, Sapporo, 062-8618, Japan
Kagawa University Hospital
Kagawa, Kita-gun, 761-0793, Japan
Kagawa Prefectural Central Hospital
Kagawa, Takamatsu, 760-8557, Japan
St. Marianna University Hospital
Kanagawa, Kawasaki, 216-8511, Japan
Kitasato University Hospital
Kanagawa, Sagamihara, 252-0375, Japan
Yokohama City University Hospital
Kanagawa, Yokohama, 236-0004, Japan
National Hospital Organization Yokohama Medical Center
Kanagawa, Yokohama, 245-8575, Japan
Kumamoto University Hospital
Kumamoto, Kumamoto, 860-8556, Japan
University Hospital Kyoto Prefectural University of Medicine
Kyoto, Kyoto, 602-8566, Japan
Shinshu University Hospital
Nagano, Matsumoto, 390-8621, Japan
Nagano Municipal Hospital
Nagano, Nagano, 381-8551, Japan
Nara Medical University Hospital
Nara, Kashihara, 634-8522, Japan
Suita Hospital
Osaka, Suita, 564-0013, Japan
Saga University Hospital
Saga, Saga, 849-8501, Japan
Hamamatsu University Hospital
Shizuoka, Hamamatsu, 431-3192, Japan
Juntendo University Shizuoka Hospital
Shizuoka, Izunokuni, 410-2295, Japan
Tokyo Medical and Dental University Hospital
Tokyo, Bunkyo-ku, 113-8519, Japan
Universiti Sains Malaysia Hospital
Kelantan, 16150, Malaysia
University of Malaya Medical Centre
Kuala Lumpur, 59100, Malaysia
Hospital Selayang
Kuala Selangor, 68100, Malaysia
Amsterdam UMC, location VUMC
Amsterdam, 1105 AZ, Netherlands
Leids Universitair Medisch Centrum (LUMC)
Leiden, 2333 ZA, Netherlands
Sint Franciscus, Locatie Vlietland
Rotterdam, 3045 PM, Netherlands
New Zealand Clinical Research (NZCR)
Auckland, 1010, New Zealand
Middlemore Clinical Trials
Papatoetoe, 2025, New Zealand
INTERCORE Medical Center
Bydgoszcz, 85-605, Poland
Synexus Poland, Branch in Czestochowa
Częstochowa, 42202, Poland
Private health care facility "Your Health EL" LLC
Elblag, 82-300, Poland
Synexus Polska SCM Sp. z o.o. Gdansku, Gdansk
Gdansk, 80-382, Poland
Synexus Polska Sp. z o.o. Oddzial w Gdyni, Gdynia
Gdynia, 81-384, Poland
University Clinical Center Professor Gibinskiego
Katowice, 40-752, Poland
University Hospital in Krakow
Krakow, 30688, Poland
Medicome Limited Liability Company
Oświęcim, 32600, Poland
Centrum Medyczne Synexus
Warsaw, 01-192, Poland
Synexus Poland, Branch in Wroclaw
Wroclaw, 50-088, Poland
ETG Zamosc
Zamość, 22400, Poland
ULS de Santa Maria, E.P.E
Lisbon, 1649-035, Portugal
Centro Hospitalar Universitário São João,EPE
Porto, 4202-451, Portugal
National University Hospital
Singapore, 119074, Singapore
Singapore General Hospital
Singapore, 168753, Singapore
Pusan National Univ. Hosp
Busan, 49241, South Korea
Keimyung University Dongsan Hospital
Daegu, 42601, South Korea
Seoul National University Hospital
Seoul, 03080, South Korea
Hospital Vall d'Hebron
Barcelona, 08035, Spain
Hospital Puerta de Hierro
Majadahonda, 28222, Spain
Hospital de Montecelo
Pontevedra, 36071, Spain
Hospital Universitario Marqués de Valdecilla
Santander, 39008, Spain
Hospital Virgen del Rocío
Seville, 41013, Spain
Hospital General Universitario de Valencia
Valencia, 46014, Spain
Chia Yi Christian Hospital
Chiayi City, 60002, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, 807, Taiwan
National Chen Kung University, Dept of Neurology
Tainan, 704, Taiwan
Chang Gung Memorial Hospital(Linkou)
Taoyuan, 333, Taiwan
Queen Elizabeth Hospital
Birmingham, B15 2TH, United Kingdom
Synexus - Hexham
Hexham, NE46 1QJ, United Kingdom
Aintree University Hospital
Liverpool, L9 7AL, United Kingdom
King's College Hospital
London, SE5 9RS, United Kingdom
Queen's Medical Centre
Nottingham, NG7 2RD, United Kingdom
Related Publications (1)
Sanyal AJ, Bedossa P, Fraessdorf M, Neff GW, Lawitz E, Bugianesi E, Anstee QM, Hussain SA, Newsome PN, Ratziu V, Hosseini-Tabatabaei A, Schattenberg JM, Noureddin M, Alkhouri N, Younes R; 1404-0043 Trial Investigators. A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis. N Engl J Med. 2024 Jul 25;391(4):311-319. doi: 10.1056/NEJMoa2401755. Epub 2024 Jun 7.
PMID: 38847460DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Boehringer Ingelheim, Call Center
- Organization
- Boehringer Ingelheim
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
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 24, 2021
First Posted
February 25, 2021
Study Start
April 27, 2021
Primary Completion
November 9, 2023
Study Completion
December 21, 2023
Last Updated
December 3, 2024
Results First Posted
December 3, 2024
Record last verified: 2024-11
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- 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.
- 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'.
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.