Research Study on Whether a Combination of 2 Medicines (NNC0194 0499 and Semaglutide) Works in People With Non-alcoholic Steatohepatitis (NASH)

Non-alcoholic Steatohepatitis Clinical Trial

Official title:

Efficacy and Safety Investigation of NNC0194-0499 Co-administered With Semaglutide in Subjects With Non-alcoholic Steatohepatitis: a Dose-ranging, Placebo Controlled Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05016882
• Other study ID #: NN9500-4656
• Secondary ID: U1111-1255-55512
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 31, 2021
• Est. completion date: March 12, 2025

Study information

• Verified date: April 2024
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is being done to see if a combination of 2 medicines (called NNC0194-0499 and semaglutide) can reduce liver damage in patients with non alcoholic steatohepatitis (NASH). NNC0194-0499 is a new medicine which works in the liver. Semaglutide is a well-known medicine, which is already used by doctors to treat type 2 diabetes in many countries. It also helps with weight loss and may reduce liver damage, and so prevent future liver complications. It works in a different way to NNC0194 0499. The 2 medicines may work better together than on their own. The study will also look at a combination of semaglutide and another weight-loss medicine called NNC0174-0833, which may be another treatment option for NASH. Each week, participants will get 2 injections. These could be 2 of the 3 medicines OR 1 of the medicines and a placebo OR 2 placebo injections. Which treatment participants get is decided by chance. A placebo is a dummy medicine which looks like the real medicine but doesn't contain any active medicine. The study will last for about 19 months. Participants will have 14 clinic visits and 9 phone calls with the study doctor. Participants will have 1 or 2 liver biopsies (tiny pieces of liver tissue) - one at the start (if participants have not had a biopsy recently) and one at the end of the study treatment. Women: Women cannot take part if pregnant, breast-feeding or planning to become pregnant during the study period.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 672
• Est. completion date: March 12, 2025
• Est. primary completion date: May 8, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Aged greater than or equal to 18 years at the time of signing informed consent. In Republic of Korea, subjects must be aged greater than or equal to 19 years. In Japan, subjects must be aged greater than or equal to 20 years. In Singapore, subjects must be aged greater than or equal to 21 years.
• Histological evidence of NASH based on a central pathologist evaluation of the baseline liver biopsy. The baseline liver biopsy can be a historical biopsy obtained within 180 days prior to Visit 1.
• Histological evidence of fibrosis stage 2, 3 or 4 according to the NASH CRN classification based on a central pathologist evaluation of the baseline liver biopsy.
• Histological non-alcoholic fatty liver disease (NAFLD) activity score (NAS) greater than or equal to 4 for subjects with F2/F3 or greater than or equal to 3 for subjects with F4 based on a central pathologist evaluation of the baseline liver biopsy. All subjects must have a score of 1 or more in steatosis, lobular inflammation and hepatocyte ballooning.

Exclusion Criteria:

• Documented causes of chronic liver disease other than NAFLD.
• Positive HBsAg, positive anti-HIV, positive HCV RNA at screening (V2A) or any known presence of HCV RNA or HBsAg within 2 years of screening (V2A).
• Presence or history of ascites more than grade 1, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis or liver transplantation at V2A.
• For subjects with F4, presence or history of gastro-oesophageal varices more than or equal to grade 2 at V3. An oesophagogastroduodenoscopy performed no more than 52 weeks prior to V3 must be available at V3.
• Known or suspected excessive consumption of alcohol (more than 20 g/day for women or more than 30 g/day for men) or alcohol dependence (assessed by the Alcohol Use Disorders Identification Test (AUDIT questionnaire)).
• Treatment with vitamin E (at doses more than or equal to 800 IU/day) or pioglitazone or medications approved for the treatment of NASH which has not been at a stable dose in the opinion of the investigator in the period from 90 days prior to V2A. In addition, for subjects with a historical liver biopsy taken more than 90 days prior to V2A, treatment should be at a stable dose in the opinion of the investigator from time of biopsy until V2A.
• Treatment with GLP-1 RAs within 90 days prior to V2A. Subjects with a historical liver biopsy taken more than 90 days prior to V2A are excluded if they receive treatment with GLP-1 RAs from time of biopsy until V2A.
• Treatment with glucose-lowering agent(s) (other than GLP-1 RAs), lipid-lowering medication or weight loss medication not stable in the opinion of the investigator in the period from 90 days prior to V2A. In addition, for subjects with a historical liver biopsy taken more than 90 days prior to V2A, treatment should be at a stable dose in the opinion of the investigator from time of biopsy until V2A.

Related Conditions & MeSH terms

• Fatty Liver
• Non-alcoholic Fatty Liver Disease
• Non-alcoholic Steatohepatitis

Intervention

Drug:
• NNC0194 0499 50 mg/mL
Patients will receive subcutaneous (s.c., under the skin) injections of NNC0194-0499 once weekly The study will last for about 19 months
• Placebo (NNC0194-0499)
Patients will receive subcutaneous (s.c., under the skin) injections of placebo once weekly The study will last for about 19 months
• Semaglutide 3 mg/mL
Patients will receive subcutaneous (s.c., under the skin) injections of semaglutide once weekly The study will last for about 19 months
• Semaglutide placebo
Patients will receive subcutaneous (s.c., under the skin) injections of semaglutide placebo once weekly The study will last for about 19 months
• NNC0174 0833 10 mg/mL
Patients will receive subcutaneous (s.c., under the skin) injections of NNC0174-0833 once weekly The study will last for about 19 months
• NNC0174 0833 placebo
Patients will receive subcutaneous (s.c., under the skin) injections of NNC0174-0833 placebo once weekly The study will last for about 19 months

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital - Hepatology- 5E291	Adelaide	South Australia
Australia	Genesis Research Services	Broadmeadow	New South Wales
Australia	Monash Health Department of Gastroenterology	Clayton	Victoria
Australia	St Vincent's Hospital	Darlinghurst	New South Wales
Australia	St Vincent's Hospital (Melbourne)	Fitzroy	Victoria
Australia	Austin Health	Heidelberg	Victoria
Australia	Nepean Hospital	Kingswood	New South Wales
Australia	The Alfred Centre - Gastroenterology	Melbourne	Victoria
Australia	Fiona Stanley Hospital - Hepatology	Murdoch	Western Australia
Australia	Westmead Hospital	Westmead	New South Wales
Belgium	Cliniques Universitaires Saint-Luc - Serv. Hépato-gastroentérology	Bruxelles
Belgium	CUB Hôpital Erasme_Brussels_0	Bruxelles
Belgium	UZA	Edegem
Belgium	UZ Gent - Department Gastro-enterology	Gent
Bulgaria	"Acibadem City Clinic MHAT Tokuda"	Sofia
Bulgaria	"DCC XX - Sofia" EOOD	Sofia
Bulgaria	UMHAT "Sv. Ivan Rilski", Clinic of Gastroenterology	Sofia
Canada	University of Calgary Liver Unit-(HMRC)	Calgary	Alberta
Canada	Toronto Liver Centre	Toronto	Ontario
Canada	GI Research Institute	Vancouver	British Columbia
Czechia	Krajská nemocice Liberec, a.s	Liberec
Denmark	Hvidovre Hospital	Hvidovre
Denmark	Abdominal Center K, Research Unit	København NV
Denmark	Odense University Hospital	Odense C
France	Centre Hospitalier Universitaire D'Angers-1	Angers
France	Ap-Hp-Hopital Beaujon	Clichy
France	Centre Hospitalier Universitaire de Lille-Hopital Claude Huriez	Lille
France	Hospices Civils de Lyon-Hopital de La Croix Rousse	Lyon Cedex 4
France	Centre Hospitalier Universitaire de Nice-Hopital de L'Archet 2	Nice
France	Aphp-Hopital La Pitie Salpetriere-4	Paris
France	Centre Hospitalier Universitaire de Nantes-Hopital Nord Laennec-1	Saint Herblain
France	Groupe Hospitalier Mutualiste Des Portes Du Sud	Venissieux
Germany	Klinik für Endokrinologie, Diabetologie und Stoffwechsel	Essen
Germany	Universitätsklinikum Schleswig-Holstein	Lübeck
Germany	Universitätsmedizin der Johannes-Gutenberg-Universität Mainz	Mainz
Germany	Universitätsklinikum Würzburg, ZIM	Würzburg
Greece	Gen Hospital of Athens Ippokrateio,B' Uni Clinic of Inte Med	Athens
Greece	Gen Hospital of Athens Laiko,1st Dpt. of Propaedeutic Inter	Athens
Greece	General Hospital of Athens "LAIKO"	Goudi, Athens
Greece	"AHEPA" University Hospital of Thessaloniki	Thessaloniki
Greece	General Hospital of Thessaloniki "Ippokrateio"	Thessaloniki
India	KLES & Prabhakar Kore Hospital and Research Centre	Belgaum	Karnatka
India	Post Graduate Institute of Medical Education & Research_Chandigarh	Chandigarh	Punjab
India	Fortis Heart Institute and Multispeciality Hospital	Chandigarh,	Punjab
India	Medanta - The Medicity Multi-Speciality Hospital, Gurugram	Gurugram	Haryana
India	Osmania General Hospital	Hyderabad	Telagana
India	Ramdev Rao Hospital	Hyderabad	Telangana
India	S.R.Kalla Memorial Gastro & General Hospital	Jaipur	Rajasthan
India	SMS Medical College & Hospital	Jaipur	Rajasthan
India	Dayanand Medical College & Hospital	Ludhiana	Punjab
India	Kasturba Medical College Hospitals (KMC Hospitals), Mangalore	Mangalore	Karnataka
India	Global Hospitals Superspeciality and Transplant center	Mumbai	Maharashtra
India	Seth GS medical college and KEM Hospital	Mumbai	Maharashtra
India	Midas Multispeciality Hospital	Nagpur	Maharashtra
India	All India Institute of medical Sciences	New Dehli	New Delhi
India	Institute of liver and Biliary Sciences	New Delhi
India	Yashoda Hospital	Secunderabad	Andhra Pradesh
India	BAPS Pramukh Swami Hospital	Surat	Gujarat
India	Surat Institute of Digestive Science	Surat	Gujarat
Italy	Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona	Ancona
Italy	Azienda Socio Sanitaria Territoriale (ASST) Papa Giovanni XXIII	Bergamo
Italy	Azieda Ospedaliero-Universitaria, Policlinico S. Orsola-Malp	Bologna
Italy	AOU Careggi Padiglione 16 San Luca, 3° piano	Firenze
Italy	Azienda Ospedaliera di Padova Clin.Med.3	Padova
Italy	AOU Pisana Stabilimento di Cisanello EDIFICIO 6, Piano 5	Pisa
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma
Italy	Policlinico Università Campus Biomedico di Roma	Rome
Japan	Chiba University Hospital_Chiba-shi, Chiba	Chiba-shi, Chiba
Japan	Fukui-ken Saiseikai Hospital, Internal Medicine	Fukui-shi, Fukui
Japan	Hamamatsu University Hospital	Hamamatsu-shi, Shizuoka
Japan	JA Hiroshima General Hospital	Hatsukaichi-shi, Hiroshima
Japan	University Hospital Kyoto Prefectual University of Medicine	Kamigyo-ku, Kyoto
Japan	St. Marianna University School of Medicine Hospital	Kawasaki-shi, Kanagawa
Japan	Kumamoto Shinto General Hospital	Kumamoto-shi, Kumamoto
Japan	Toranomon Hospital, Hepatology	Minato-ku, Tokyo
Japan	Kawasaki Medical School General Medical Center	Okayama-shi, Okayama
Japan	Saga University Hospital_Liver Center	Saga-shi, Saga
Japan	Sendai Kousei Hospital	Sendai-shi, Miyagi
Japan	Saiseikai Suita Hospital, Gastroenterology	Suita-shi, Osaka
Japan	Ehime University Hospital	Toon-shi, Ehime
Japan	Saiseikai Wakayama Hospital	Wakayama-shi, Wakayama
Japan	Yokohama City University Hospital, Gastrointestinal Medicine	Yokohama-shi, Kanagawa
Korea, Republic of	Korea University Ansan Hospital	Ansan	Gyeonggi-do
Korea, Republic of	Keimyung University Dongsan Medical Center	Daegu
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Yeungnam Univ. Medical Center	Daegu
Korea, Republic of	Wonju Severance Christian Hospital	Gangwon-do
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	SMG-SNU Boramae Medical Center	Seoul
Malaysia	Hospital Selayang	Batu Caves
Malaysia	Hospital Universiti Sains Malaysia	Kota Bharu	Kelantan
Malaysia	University Malaya Medical Centre	Kuala Lumpur	Wilayah Persekutuan Kuala Lumpur
Poland	Spolka Lekarzy Intercor Sp. z o.o.	Bydgoszcz
Poland	Clinical Medical Research Korfantego - Ambulatoryjna Opieka	Katowice
Poland	Uniwersyteckie Centrum Kliniczne im. Prof. K. Gibinskiego Sl	Katowice
Poland	Krakowskie Centrum Medyczne Sp. z o.o.	Krakow
Poland	"LANDA" Katarzyna Agata Landa	Kraków
Poland	ID Clinic Arkadiusz Pisula	Myslowice	Malopolskie
Poland	Centrum Medyczne Medyk Sp. z o.o.	Rzeszow
Poland	Ko-Med Nova Sp.zo.o. STASZOW	Staszow
Poland	Centrum Badan Klinicznych	Wroclaw
Poland	EMC Instytut Medyczny S.A.	Wroclaw
Poland	FutureMeds Sp. z o.o.	Wroclaw
Portugal	Centro Hospitalar Lisboa Norte	Lisboa
Portugal	Unidade Local de Saúde de Matosinhos	Matosinhos
Puerto Rico	FDI Clinical Research	San Juan
Russian Federation	Penza Regional Clinical Hospital named after N.N. Burdenko	Penza
Singapore	Changi General Hospital	Singapore
Singapore	National University Hospital_TBD	Singapore
Singapore	Singapore General Hospital	Singapore
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda
Spain	Complejo Hospitalario de Pontevedra - Hospital de Montecelo	Pontevedra
Spain	Hospital Universitario Marqués de Valdecilla	Santander
Spain	Hospital Virgen del Rocío	Sevilla
Spain	Hospital Clínico de Valladolid	Valladolid
Taiwan	Ditmanson Medical Foundation Chia-Yi Christian Hospital	Chiayi City
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaoshiung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Turkey	T.C. Saglik Bakanligi Adana Sehir Egitim ve Arastirma Hastan	Adana
Turkey	Gazi University Medical Faculty	Ankara
Turkey	Hacettepe Universitesi Tip Fakültesi- Gastroenteroloji	Ankara
Turkey	Bezmialem Vakif Universitesi Tip Fakultesi Hastanesi-Gastroe	Istanbul
Turkey	Marmara Univ. Pendik Gastroenterology	Istanbul
Turkey	Kocaeli Universitesi Tip Fakültesi Gastroenteroloji ve Hepat	Kocaeli
United Kingdom	Royal Devon & Exeter NHS Foundation Trust	Exeter
United States	Texas Clin Res Inst, LLC	Arlington	Texas
United States	Digestive Healthcare of Georgia	Atlanta	Georgia
United States	Piedmont Healthcare	Atlanta	Georgia
United States	Mercy Medical Center, GI Research	Baltimore	Maryland
United States	Walter Reed Nat Mil Md Ctr	Bethesda	Maryland
United States	The Institute for Liver Health	Chandler	Arizona
United States	Univ Hosp Cleveland Med Ctr	Cleveland	Ohio
United States	Peak Gastro Assoc-Col Springs	Colorado Springs	Colorado
United States	Ohio State Univ Wexner Med Ctr	Columbus	Ohio
United States	Liver Ins@ Mthdist DTX Med Cen	Dallas	Texas
United States	Geisinger Clinic	Danville	Pennsylvania
United States	Henry Ford Hospital_Detroit	Detroit	Michigan
United States	Integrity Clinical Research, LLC	Doral	Florida
United States	Inova Fairfax Medical Campus	Falls Church	Virginia
United States	AIG Digestive Disease Research	Florham Park	New Jersey
United States	Hartford Hsptl_Hartford	Hartford	Connecticut
United States	Digestive Health Res-TSMC	Hermitage	Tennessee
United States	Pennsylvania State University	Hershey	Pennsylvania
United States	Miguel Rebollar PA	Hialeah	Florida
United States	Tandem Clinical Research - Houma	Houma	Louisiana
United States	Liver Specialists of Texas	Houston	Texas
United States	North AL Health Res, LLC	Huntsville	Alabama
United States	Nature Coast Clinical Research_Inverness	Inverness	Florida
United States	UF Hepatology Jacksonville	Jacksonville	Florida
United States	Kansas City Research Institute	Kansas City	Missouri
United States	University Of Kansas Hospital	Kansas City	Kansas
United States	UCSD NAFLD Research Center	La Jolla	California
United States	Florida Research Institute, LLC	Lakewood Ranch	Florida
United States	OM Research LLC	Lancaster	California
United States	Gastroenterology Assoc_ CGA	Macon	Georgia
United States	Gastroint Spec of Georgia	Marietta	Georgia
United States	Tandem Clinical Research	Marrero	Louisiana
United States	Optimus U, Corp	Miami	Florida
United States	Univ of Miami/Schiff Ctr	Miami	Florida
United States	Quality Medical Research	Nashville	Tennessee
United States	NYU Grossman School of Med	New York	New York
United States	Weill Cornell Med Coll-NYPH	New York	New York
United States	Inst-Liver Hlth dba AZ Liver H	Peoria	Arizona
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	UPMC Center for Liver Diseases	Pittsburgh	Pennsylvania
United States	UPMC_Center for Liver Care	Pittsburgh	Pennsylvania
United States	Stanford Medicine	Redwood City	California
United States	Bon Secours Richmond Community Hospital LLC	Richmond	Virginia
United States	Gastroent Consult of SW VA	Roanoke	Virginia
United States	Texas Diabetes & Endocinology	Round Rock	Texas
United States	UC Davis Hlth -Midtwn Ambu Cen	Sacramento	California
United States	Amer. Rrsch Corp-TX Liver Inst	San Antonio	Texas
United States	Covenant Metabolic Specialists LLC	Sarasota	Florida
United States	Liver Institute NW	Seattle	Washington
United States	Swedish med ctr org trans-lvr ctr	Seattle	Washington
United States	Louisiana Research Center, LLC	Shreveport	Louisiana
United States	Digestive Research Alliance of Michiana	South Bend	Indiana
United States	DSI Research,LLC	Springboro	Ohio
United States	Kansas Medical Clinic, PA	Topeka	Kansas
United States	Del Sol Research Management, LLC	Tucson	Arizona
United States	Impact Research	Waco	Texas
United States	Digestive Hlth Res of N Texas	Wichita Falls	Texas
United States	Florida Medical Clinic, LLC	Zephyrhills	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Bulgaria,  Canada,  Czechia,  Denmark,  France,  Germany,  Greece,  India,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Poland,  Portugal,  Puerto Rico,  Russian Federation,  Singapore,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement in liver fibrosis and no worsening of NASH (Yes/No)	Count of subjects Improvement in fibrosis is defined as greater than or equal to 1 grade improvement on the NASH CRN fibrosis scale	From baseline (week 0) to week 52
Secondary	Resolution of steatohepatitis and no worsening of liver fibrosis (Yes/No)	Count of subjects Resolution of steatohepatitis is defined as a NAS of 0-1 for inflammation, 0 for ballooning and any value for steatosis according to NASH CRN52. Fibrosis is graded on the NASH CRN (Non-Alcoholic Steatohepatitis Clinical Research Network) fibrosis scale from 0 to 4.	From baseline (week 0) to week 52
Secondary	Improvement in steatohepatitis with at least a 2-point reduction in NAS and no worsening of fibrosis (Yes/No)	Count of subjects The 2-point reduction must include at least a 1-point reduction in either lobular inflammation or hepatocellular ballooning.	From baseline (week 0) to week 52
Secondary	Change in histology-assessed liver collagen proportionate area	Ratio to baseline	From baseline (week 0) to week 52
Secondary	Resolution of steatohepatitis and improvement in liver fibrosis (Yes/No)	Count of subjects Resolution of steatohepatitis is defined as an NAS score of 0-1 for inflammation, 0 for ballooning and any value for steatosis (according to NASH CRN).; Improvement in fibrosis is defined as greater than or equal to 1 grade improvement on the NASH CRN fibrosis scale	From baseline (week 0) to week 52
Secondary	Improvement in liver fibrosis (Yes/No)	Count of subjects Improvement in fibrosis is defined as greater than or equal to 1 grade improvement on the NASH CRN fibrosis scale	From baseline (week 0) to week 52
Secondary	Progression of liver fibrosis (Yes/No)	Count of subjects For subjects with fibrosis stage 2 or 3 at baseline	From baseline (week 0) to week 52
Secondary	Worsening in steatohepatitis (Yes/No)	Count of subjects Worsening in steatohepatitis is defined as increase in NAS score for ballooning, inflammation or steatosis	From baseline (week 0) to week 52
Secondary	Improvement in ballooning (Yes/No)	Count of subjects	From baseline (week 0) to week 52
Secondary	Improvement in inflammation (Yes/No)	Count of subjects	From baseline (week 0) to week 52
Secondary	Improvement in steatosis (Yes/No)	Count of subjects	From baseline (week 0) to week 52
Secondary	Change in ALT (alanine aminotransferase)	Ratio to baseline	From baseline (week 0) to week 52
Secondary	Change in AST (aspartate aminotransferase)	Ratio to baseline	From baseline (week 0) to week 52
Secondary	Change in inflammation assessed by HsCRP (high sensitivity C-reactive protein)	Ratio to baseline	From baseline (week 0) to week 52
Secondary	Change in ELF (Enhanced Liver Fibrosis) score	Logarithm	From baseline (week 0) to week 52
Secondary	Change in HbA1c. For subjects with type 2 diabetes	%-points (absolute change)	From baseline (week 0) to week 52
Secondary	Change in triglycerides	Ratio to baseline	From baseline (week 0) to week 52
Secondary	Change in free fatty acids	Ratio to baseline	From baseline (week 0) to week 52
Secondary	Change in LDL (low density lipoprotein) cholesterol	Ratio to baseline	From baseline (week 0) to week 52
Secondary	Change in HDL (high density lipoprotein) cholesterol	Ratio to baseline	From baseline (week 0) to week 52
Secondary	Relative change in body weight	Percentage	From baseline (week 0) to week 52
Secondary	Change in SF-36 (36-item Short Form Survey) bodily pain	Points	From baseline (week 0) to week 52
Secondary	Change in NASH-CHECK (patient-reported outcome measure for non-alcoholic steatohepatitis)pain	Points	From baseline (week 0) to week 52
Secondary	Change in PROMIS (Patient-Reported Outcomes Measurement Information System) Fatigue score	Points	From baseline (week 0) to week 52
Secondary	Number of treatment emergent adverse events (TEAEs)	Count	From baseline (week 0) to week 59