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

Non-alcoholic Steatohepatitis (NASH) Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04771273
• Other study ID #: 1404-0043
• Secondary ID: 2020-002723-11
• Status: Completed
• Phase: Phase 2
• Start date: April 27, 2021
• Est. completion date: December 21, 2023

Study information

• Verified date: April 2024
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 295
• Est. completion date: December 21, 2023
• Est. primary completion date: November 9, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Fatty Liver
• Non-alcoholic Fatty Liver Disease
• Non-alcoholic Steatohepatitis (NASH)

Intervention

Drug:
• BI 456906
BI 456906
• Placebo
Placebo

Locations

Country	Name	City	State
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Gold Coast University Hospital	Southport	Queensland
Austria	Medical University of Graz State Hospital - University Hospital Graz	Graz
Austria	Medical University of Innsbruck	Innsbruck
Austria	Ordensklinikum Linz GmbH - Barmherzige Schwestern	Linz
Belgium	Edegem - UNIV UZ Antwerpen	Edegem
Canada	Ecogene-21	Chicoutimi	Quebec
Canada	University Hospital (LHSC)	London	Ontario
Canada	Toronto Liver Centre	Toronto	Ontario
China	Beijing Ditan Hospital Capital Medical University	Beijing
China	Beijing Friendship Hospital	Beijing
China	Beijing Tsinghua Changgung Hospital	Beijing
China	Peking University People's Hospital	Beijing
China	The First Hospital of Jilin University	Changchun
China	NanFang Hosptial	Guangzhou
China	The First Afiliated Hospital, Sun Yet-sen University	Guangzhou
China	Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine	Hangzhou
China	First People's hospital of Yunann Province	Kunming
China	The Second Hospital of Nanjing	Nanjing
China	Shanghai Public Health Clinical Center	Shanghai
China	Tianjin Third Central Hospital	Tianjin
China	The First Affiliated Hospital of Wenzhou Med College	Wenxzhou
Czechia	Regional Hospital Liberec	Liberec
Czechia	General Faculty Hospital, Prague	Prague
France	HOP l'Archet	Nice
France	HOP La Pitié Salpêtrière	Paris
France	HOP Haut-Lévêque	Pessac
France	HOP Civil	Strasbourg
Germany	Universitätsklinikum Aachen, AöR	Aachen
Germany	Synexus Clinical Research GmbH	Berlin
Germany	Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH	Bochum
Germany	Universitätsklinikum Düsseldorf	Düsseldorf
Germany	Synexus Clinical Research GmbH	Frankfurt
Germany	Synexus Clinical Research GmbH	Leipzig
Germany	Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz
Germany	Universitätsklinikum Mannheim GmbH	Mannheim
Germany	Universitätsklinikum Ulm	Ulm
Greece	Attikon University Hospital	Haidari-Athens
Greece	General Hospital of Thessaloniki "Hippokrateio"	Thessaloniki
Hong Kong	Prince of Wales Hospital	Hong Kong
Hong Kong	Queen Mary Hospital	Hong Kong
Hungary	Fed.St. Istvan&Szent Laszlo Hospital	Budapest
Hungary	Synexus Hungary Healthcare Service Ltd.	Budapest
Hungary	Synexus Hungary Healthcare Service Ltd	Gyula
Israel	Shaare Zedek Medical Center, Jerusalem 91031	Jerusalem
Israel	Western Galilee Hospital	Nahariya
Israel	Rabin Medical Center Beilinson	Petach Tikva
Israel	Sourasky Medical Center	Tel Aviv
Israel	The Chaim Sheba Medical Center	Tel-Hashomer
Italy	Ospedale Civile di Baggiovara	Baggiovara (MO)
Italy	A.O. Univ. Policlinico "Paolo Giaccone"	Palermo
Italy	Poli Univ A. Gemelli	Roma
Italy	Istituto Clinico Humanitas	Rozzano (MI)
Italy	IRCCS Ospedale "Casa Sollievo della Sofferenza"	SAN Giovanni Rotondo (FG)
Italy	AO Città della Salute e Scienza	Torino
Japan	Ehime University Hospital	Ehime, Toon
Japan	Fukuiken Saiseikai Hospital	Fukui, Fukui
Japan	Kurume University Hospital	Fukuoka, Kurume
Japan	Ogaki Municipal Hospital	Gifu, Ogaki
Japan	Japan Community Health Care Organization Hokkaido Hospital	Hokkaido, Sapporo
Japan	Kagawa University Hospital	Kagawa, Kita-gun
Japan	Kagawa Prefectural Central Hospital	Kagawa, Takamatsu
Japan	St. Marianna University Hospital	Kanagawa, Kawasaki
Japan	Kitasato University Hospital	Kanagawa, Sagamihara
Japan	National Hospital Organization Yokohama Medical Center	Kanagawa, Yokohama
Japan	Yokohama City University Hospital	Kanagawa, Yokohama
Japan	Kumamoto University Hospital	Kumamoto, Kumamoto
Japan	University Hospital Kyoto Prefectural University of Medicine	Kyoto, Kyoto
Japan	Shinshu University Hospital	Nagano, Matsumoto
Japan	Nagano Municipal Hospital	Nagano, Nagano
Japan	Nara Medical University Hospital	Nara, Kashihara
Japan	Suita Hospital	Osaka, Suita
Japan	Saga University Hospital	Saga, Saga
Japan	Hamamatsu University Hospital	Shizuoka, Hamamatsu
Japan	Juntendo University Shizuoka Hospital	Shizuoka, Izunokuni
Japan	Tokyo Medical and Dental University Hospital	Tokyo, Bunkyo-ku
Korea, Republic of	Pusan National Univ. Hosp	Busan
Korea, Republic of	Keimyung University Dongsan Hospital	Daegu
Korea, Republic of	Seoul National University Hospital	Seoul
Malaysia	Universiti Sains Malaysia Hospital	Kelantan
Malaysia	University of Malaya Medical Centre	Kuala Lumpur
Malaysia	Hospital Selayang	Selangor
Netherlands	Amsterdam UMC, Locatie AMC	Amsterdam
Netherlands	Leids Universitair Medisch Centrum (LUMC)	Leiden
Netherlands	Sint Franciscus, Locatie Vlietland	Rotterdam
New Zealand	New Zealand Clinical Research (NZCR)	Auckland
New Zealand	Middlemore Clinical Trials	Papatoetoe
Poland	INTERCORE Medical Center	Bydgoszcz
Poland	Synexus Poland, Branch in Czestochowa	Czestochowa
Poland	Private health care facility "Your Health EL" LLC	Elblag
Poland	Synexus Polska SCM Sp. z o.o. Gdansku, Gdansk	Gdansk
Poland	Synexus Polska Sp. z o.o. Oddzial w Gdyni, Gdynia	Gdynia
Poland	University Clinical Center Professor Gibinskiego	Katowice
Poland	University Hospital in Krakow	Krakow
Poland	Medicome Limited Liability Company	Oswiecim
Poland	Centrum Medyczne Synexus	Warszawa
Poland	Synexus Poland, Branch in Wroclaw	Wroclaw
Poland	ETG Zamosc	Zamosc
Portugal	ULS de Santa Maria, E.P.E	Lisboa
Portugal	Centro Hospitalar Universitário São João,EPE	Porto
Singapore	National University Hospital	Singapore
Singapore	Singapore General Hospital	Singapore
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Puerta de Hierro	Majadahonda
Spain	Hospital de Montecelo	Pontevedra
Spain	Hospital Universitario Marqués de Valdecilla	Santander
Spain	Hospital Virgen del Rocío	Sevilla
Spain	Hospital General Universitario de Valencia	Valencia
Taiwan	Chia Yi Christian Hospital	ChiaYi
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	National Chen Kung University, Dept of Neurology	Tainan
Taiwan	Chang Gung Memorial Hospital(Linkou)	Taoyuan County
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	Synexus - Hexham	Hexham
United Kingdom	Aintree University Hospital	Liverpool
United Kingdom	King's College Hospital	London
United Kingdom	Queen's Medical Centre	Nottingham
United States	Texas Clinical Research Institute, LLC	Arlington	Texas
United States	Texas Liver Institute	Austin	Texas
United States	Delta Research Partners, LLC	Bastrop	Louisiana
United States	National Diabetes and Obesity Research Institute	Biloxi	Mississippi
United States	South Texas Research Institute	Brownsville	Texas
United States	Peak Gastroenterology Associates	Colorado Springs	Colorado
United States	Northeast GI Research Division	Concord	North Carolina
United States	Southern California Research Center	Coronado	California
United States	Integrity Clinical Research, LLC	Doral	Florida
United States	South Texas Research Institute	Edinburg	Texas
United States	NECCR PrimaCare Research, LLC	Fall River	Massachusetts
United States	AIG Digestive Disease Research	Florham Park	New Jersey
United States	Gastrointestinal Associates	Flowood	Mississippi
United States	Covenant Metabolic Specialists, LLC	Fort Myers	Florida
United States	Digestive Diseases Research Center	Greenwood	South Carolina
United States	Digestive Health Research, LLC	Hermitage	Tennessee
United States	Houston Methodist Hospital	Houston	Texas
United States	Velocity Clinical Research	Huntington Park	California
United States	North Alabama Health Research, LLC	Huntsville	Alabama
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Centex Studies, Inc.	Lake Charles	Louisiana
United States	Gastrointestinal Specialists of Georgia	Marietta	Georgia
United States	Tandem Clinical Research	Marrero	Louisiana
United States	Optimus U Corporation	Miami	Florida
United States	Sanchez Clinical Research ,Inc	Miami	Florida
United States	Lucas Research, Inc.	Morehead City	North Carolina
United States	Ocala GI Research	Ocala	Florida
United States	Omega Research Orlando, LLC	Orlando	Florida
United States	Velocity Clinical Research	Panorama City	California
United States	Virginia Commonwealth University	Richmond	Virginia
United States	American Research Corporation at the Texas Liver Institute	San Antonio	Texas
United States	Pinnacle Clinical Research	San Antonio	Texas
United States	Quest Clinical Research	San Francisco	California
United States	Covenant Metabolic Specialists, LLC	Sarasota	Florida
United States	Digestive Research Alliance of Michiana	South Bend	Indiana
United States	Palmetto Clinical Research	Summerville	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  China,  Czechia,  France,  Germany,  Greece,  Hong Kong,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Netherlands,  New Zealand,  Poland,  Portugal,  Singapore,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Absolute and relative change of liver fat content from baseline after 48 weeks of treatment assessed by MRI-PDFF		Week 48
Secondary	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
Secondary	Absolute change from baseline in NAS after 48 weeks of treatment assessed by liver biopsy		Week 48

External Links

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