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

NCT ID: NCT04771273

Last Updated: 2024-12-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 295 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-27
• Study Completion Date: 2023-12-21

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.

Conditions

Non-alcoholic Steatohepatitis (NASH)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Survodutide 2.4 mg - planned maintenance treatment

Group Type: EXPERIMENTAL

Survodutide

Intervention Type: DRUG

Survodutide

Survodutide 4.8 mg - planned maintenance treatment

Group Type: EXPERIMENTAL

Survodutide

Intervention Type: DRUG

Survodutide

Survodutide 6.0 mg - planned maintenance treatment

Group Type: EXPERIMENTAL

Survodutide

Intervention Type: DRUG

Survodutide

Placebo - planned maintenance treatment

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

Survodutide

Survodutide

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Other Intervention Names

BI 456906

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

North Alabama Health Research, LLC

Huntsville, Alabama, United States

Southern California Research Center

Coronado, California, United States

Velocity Clinical Research

Huntington Park, California, United States

Velocity Clinical Research

Panorama City, California, United States

Quest Clinical Research

San Francisco, California, United States

Peak Gastroenterology Associates

Colorado Springs, Colorado, United States

Integrity Clinical Research, LLC

Doral, Florida, United States

Covenant Metabolic Specialists, LLC

Fort Myers, Florida, United States

Optimus U Corporation

Miami, Florida, United States

Sanchez Clinical Research ,Inc

Miami, Florida, United States

Ocala GI Research

Ocala, Florida, United States

Omega Research Orlando, LLC

Orlando, Florida, United States

Covenant Metabolic Specialists, LLC

Sarasota, Florida, United States

Gastrointestinal Specialists of Georgia

Marietta, Georgia, United States

Digestive Research Alliance of Michiana

South Bend, Indiana, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Delta Research Partners, LLC

Bastrop, Louisiana, United States

Centex Studies, Inc.

Lake Charles, Louisiana, United States

Tandem Clinical Research

Marrero, Louisiana, United States

NECCR PrimaCare Research, LLC

Fall River, Massachusetts, United States

National Diabetes and Obesity Research Institute

Biloxi, Mississippi, United States

Gastrointestinal Associates

Flowood, Mississippi, United States

AIG Digestive Disease Research

Florham Park, New Jersey, United States

Northeast GI Research Division

Concord, North Carolina, United States

Lucas Research, Inc.

Morehead City, North Carolina, United States

Digestive Diseases Research Center

Greenwood, South Carolina, United States

Palmetto Clinical Research

Summerville, South Carolina, United States

Digestive Health Research, LLC

Hermitage, Tennessee, United States

Texas Clinical Research Institute, LLC

Arlington, Texas, United States

Texas Liver Institute

Austin, Texas, United States

South Texas Research Institute

Brownsville, Texas, United States

South Texas Research Institute

Edinburg, Texas, United States

Houston Methodist Hospital

Houston, Texas, United States

American Research Corporation at the Texas Liver Institute

San Antonio, Texas, United States

Pinnacle Clinical Research

San Antonio, Texas, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Gold Coast University Hospital

Southport, Queensland, Australia

Monash Medical Centre

Clayton, Victoria, Australia

Royal Melbourne Hospital

Parkville, Victoria, Australia

Medical University of Graz State Hospital - University Hospital Graz

Graz, , Austria

Medical University of Innsbruck

Innsbruck, , Austria

Ordensklinikum Linz GmbH - Barmherzige Schwestern

Linz, , Austria

Edegem - UNIV UZ Antwerpen

Edegem, , Belgium

University Hospital (LHSC)

London, Ontario, Canada

Toronto Liver Centre

Toronto, Ontario, Canada

Ecogene-21

Chicoutimi, Quebec, Canada

Beijing Ditan Hospital Capital Medical University

Beijing, , China

Beijing Tsinghua Changgung Hospital

Beijing, , China

Peking University People's Hospital

Beijing, , China

Beijing Friendship Hospital

Beijing, , China

The First Hospital of Jilin University

Changchun, , China

The First Afiliated Hospital, Sun Yet-sen University

Guangzhou, , China

NanFang Hosptial

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, , China

Regional Hospital Liberec

Liberec, , Czechia

General Faculty Hospital, Prague

Prague, , Czechia

HOP l'Archet

Nice, , France

HOP La Pitié Salpêtrière

Paris, , France

HOP Haut-Lévêque

Pessac, , France

HOP Civil

Strasbourg, , France

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, , Germany

Attikon University Hospital

Haidari-Athens, , Greece

General Hospital of Thessaloniki "Hippokrateio"

Thessaloniki, , Greece

Prince of Wales Hospital

Hong Kong, , Hong Kong

Queen Mary Hospital

Hong Kong, , Hong Kong

Synexus Hungary Healthcare Service Ltd.

Budapest, , Hungary

Fed.St. Istvan&Szent Laszlo Hospital

Budapest, , Hungary

Synexus Hungary Healthcare Service Ltd

Gyula, , Hungary

Shaare Zedek Medical Center, Jerusalem 91031

Jerusalem, , Israel

Western Galilee Hospital

Nahariya, , Israel

Rabin Medical Center Beilinson

Petah Tikva, , Israel

Sourasky Medical Center

Tel Aviv, , Israel

The Chaim Sheba Medical Center

Tel Litwinsky, , Israel

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, , Italy

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

Yokohama City University Hospital

Kanagawa, Yokohama, , Japan

National Hospital Organization Yokohama Medical Center

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, , Japan

Universiti Sains Malaysia Hospital

Kelantan, , Malaysia

University of Malaya Medical Centre

Kuala Lumpur, , Malaysia

Hospital Selayang

Kuala Selangor, , Malaysia

Amsterdam UMC, location VUMC

Amsterdam, , Netherlands

Leids Universitair Medisch Centrum (LUMC)

Leiden, , Netherlands

Sint Franciscus, Locatie Vlietland

Rotterdam, , Netherlands

New Zealand Clinical Research (NZCR)

Auckland, , New Zealand

Middlemore Clinical Trials

Papatoetoe, , New Zealand

INTERCORE Medical Center

Bydgoszcz, , Poland

Synexus Poland, Branch in Czestochowa

Częstochowa, , 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

Oświęcim, , Poland

Centrum Medyczne Synexus

Warsaw, , Poland

Synexus Poland, Branch in Wroclaw

Wroclaw, , Poland

ETG Zamosc

Zamość, , Poland

ULS de Santa Maria, E.P.E

Lisbon, , Portugal

Centro Hospitalar Universitário São João,EPE

Porto, , Portugal

National University Hospital

Singapore, , Singapore

Singapore General Hospital

Singapore, , Singapore

Pusan National Univ. Hosp

Busan, , South Korea

Keimyung University Dongsan Hospital

Daegu, , South Korea

Seoul National University Hospital

Seoul, , South Korea

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

Seville, , Spain

Hospital General Universitario de Valencia

Valencia, , Spain

Chia Yi Christian Hospital

Chiayi City, , Taiwan

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

National Chen Kung University, Dept of Neurology

Tainan City, , Taiwan

Chang Gung Memorial Hospital(Linkou)

Taoyuan, , Taiwan

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 Kingdom

Countries

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

References

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.

Reference Type: DERIVED

PMID: 38847460 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.mystudywindow.com

Related Info

Other Identifiers

2020-002723-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1404-0043

Identifier Type: -

Identifier Source: org_study_id