A Study to Test Safety and Efficacy of 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.

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: Non-alcoholic Steatohepatitis (NASH)
• Intervention / Treatment: Drug: Placebo; Drug: BI 456906

• Study Type: Interventional
• Enrollment (Actual): 295
• Phase: Phase 2

Contacts and Locations

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
    • Universitätsklinikum Düsseldorf
  • 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
    • Universitatsklinikum 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, locatie AMC
  • 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 Marques 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, 80756
    • 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

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

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo
Experimental: BI 456906 low dose; low dose	Drug: BI 456906; BI 456906
Experimental: BI 456906 medium dose; medium dose	Drug: BI 456906; BI 456906
Experimental: BI 456906 high dose; high dose	Drug: BI 456906; BI 456906

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with histological improvement of NASH (NAS reduction of 2 or more points) after 48 weeks of treatment	Non-alcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) represents the sum of scores for steatosis (0-3), lobular inflammation (0-3) and ballooning (0-2); the total score ranges from 0 to 8. Improvement in histological findings is defined as a composite of: Improvement in NASH is defined as a composite of: Decrease of at least 2 points in NAS with at least 1 point decrease in NAS subscore of either lobular inflammation or ballooning AND; No worsening of fibrosis, defined as absence of any increase in the fibrosis stage.	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement of liver fat content (yes/no) defined as at least 30 percent (%) relative reduction in liver fat content after 48 weeks of treatment compared to baseline	Assessment will be done by magnetic resonance imaging proton density fat fraction measurement (MRI-PDFF)	Week 48
Absolute and relative change of liver fat content from baseline after 48 weeks of treatment assessed by MRI-PDFF		Week 48
Improvement of fibrosis (yes/no) defined as at least one stage decrease in fibrosis stage after 48 weeks of treatment assessed by liver biopsy		Week 48
Absolute change from baseline in NAS after 48 weeks of treatment assessed by liver biopsy		Week 48

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

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): March 19, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• 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