Study to Evaluate the Efficacy and Safety of CC-90001 in Participants With Non-alcoholic Steatohepatitis (NASH) and Liver Fibrosis

Liver Cirrhosis Clinical Trial

Official title:

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Dose-Finding Study To Evaluate The Efficacy and Safety Of CC-90001 In Subjects With Non-Alcoholic Steatohepatitis (NASH) and Liver Fibrosis

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04048876
• Other study ID #: CC-90001-NASH-001
• Secondary ID: U1111-1235-32342
• Status: Terminated
• Phase: Phase 2
• Start date: August 14, 2019
• Est. completion date: September 28, 2021

Study information

• Verified date: June 2023
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 2, randomized, double-blind, placebo-controlled, multicenter, multinational, dose-finding study evaluating the efficacy of three treatment doses of CC-90001 compared with placebo, in Non-alcoholic Steatohepatitis (NASH) participants with Stage 2, Stage 3 liver fibrosis.

This study is designed to assess response to treatment on measures of fibrosis and other efficacy parameters. It will also assess dose response and overall safety.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 56
• Est. completion date: September 28, 2021
• Est. primary completion date: September 28, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Key Inclusion Criteria Diagnosis of non-alcoholic steatohepatitis (NASH) with presence of Stage 2, Stage 3 fibrosis based of the non-alcoholic steatohepatitis (NASH) Clinical Research Network (CRN) Histologic Scoring System and a nonalcoholic fatty liver disease (NAFLD) Activity Score (NAS) of 4 or higher

Exclusion Criteria:

• Key Exclusion Criteria

1. History or evidence of decompensated liver disease,

2. Hepatitis and fibrosis more likely related to etiologies other than non-alcoholic steatohepatitis (NASH).

3. Participant has urine ethyl glucuronide (EtG) > 500 ng/mL at Screening.

4. History or positive screen for human immunodeficiency virus (HIV) infection or congenital or human immunodeficiency virus (HIV)-unrelated acquired immunodeficiencies (eg, common variable immunodeficiency [CVID]).

5. History of hepatitis B and/or hepatitis C.

6. History of malignancy within the last 5 years (exceptions: excised and cured basal/squamous cell skin carcinomas and cervical carcinoma in situ).

7. Pregnancy or lactation.

Related Conditions & MeSH terms

• Fatty Liver
• Fibrosis
• Liver Cirrhosis
• Liver Diseases
• Non-alcoholic Fatty Liver Disease

Intervention

Drug:
• CC-90001
oral
• Placebo
oral

Locations

Country	Name	City	State
Australia	University of Sydney - Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Nepean Hospital	Kingswood	New South Wales
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Mater Hospital Brisbane	South Brisbane	Queensland
Canada	University of Calgary, Cumming School of Medicine	Calgary	Alberta
Canada	South Edmonton Gastroenterology	Edmonton	Alberta
Canada	Toronto Center for Liver Disease - Francis Family Liver Clinic	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
France	CHU d'Angers	Angers
France	Assistance Publique - Hopitaux de Paris - Hopital Beaujon	Clichy cedex
France	Hopital de la Croix-Rousse	Lyon
France	Assistance Publique - Hopitaux de Paris - Hopital Cochin	Paris
France	Assistance Publique - Hopitaux de Paris - Hopital Universitaire Pitie Salpetriere	Paris CEDEX 13
France	Hopital Haut Leveque	Pessac Cedex
France	Centre Hospitalier Universitaire de Rennes - Hopital de Pontchaillou	Rennes cedex 09
France	Hopital Hautepierre	Strasbourg
France	Local Institution - 356	Strasbourg
Germany	Universitaetsklinikum der RWTH Aachen	Aachen
Germany	Johann Wolfgang Goethe University Hospital	Frankfurt am Main
Germany	Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz	Mainz
Germany	Universitaetsklinikum Muenster	Muenster
Japan	Hamamatsu University Hospital	Hamamatsu
Japan	Local Institution - 604	Hamamatsu
Japan	Local Institution - 608	Kashihara
Japan	Nara Medical University Hospital	Kashihara
Japan	Local Institution - 601	Kawasaki
Japan	Shin-Yurigaoka General Hospital	Kawasaki
Japan	Kurume University Hospital	Kurume, Fukuoka
Japan	Local Institution - 607	Kurume, Fukuoka
Japan	Local Institution - 615	Kyoto-City
Japan	University Hospital, Kyoto Prefectural University of Medicine	Kyoto-City
Japan	Japanese Red Cross Musashino Hospital	Musashino
Japan	Local Institution - 602	Musashino
Japan	Aichi Medical University Hospital	Nagakute
Japan	Local Institution - 611	Nagakute
Japan	Local Institution - 613	Ogaki
Japan	Ogaki Municipal Hospital	Ogaki
Japan	Local Institution - 603	Osaka-Fu
Japan	Osaka University Hospital OUH	Osaka-Fu
Japan	Local Institution - 609	Saga
Japan	Saga University Hospital	Saga
Japan	Belland General Hospital	Sakai-shi
Japan	Local Institution - 605	Sakai-shi
Japan	Local Institution - 612	Suita
Japan	Saiseikai Suita Hospital	Suita
Japan	Local Institution - 600	Yokohama, Kanagawa
Japan	Yokohama City University Hospital	Yokohama, Kanagawa
Korea, Republic of	Soon Chun Hyang University Hospital Bucheon	Bucheon-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Boramae Medical Center	Seoul
Korea, Republic of	Hanyang University Seoul Hospital	Seoul
Korea, Republic of	Korea University Hospital at Guro	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Yonsei University Wonju Severance Christian Hospital	Wonju-si
Poland	Katowice (DRS)Synexus Polska Sp. z o.o. Oddzial w Katowicach	Katowice
Poland	Samodzielny Publiczny Centralny Szpital Kliniczny Im Prof. Kornela Gibinskiego	Katowice
Poland	Krakow Medical Center LLC	Krakow
Poland	Lodz (DRS)Synexus Polska Sp. Z o.o. Oddzial w Lodzi	Lodz
Poland	Wojewodzki Specjalistyczny Szpital im. dr Wladyslawa Bieganskiego	Lodz
Poland	ID Clinic	Myslowice
Poland	Local Institution - 453	Myslowice
Poland	Synexus SCM Sp. z o.o. Oddz. Warszawa	Warszawa
Spain	Hospital Val d'Hebron	Barcelona
Spain	University Hospital of Girona Dr. Josep Trueta	Girona
Spain	Parc Tauli Hospital Universitari	Sabadell (Barcelona)
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital Virgen del Rocio	Sevilla
United Kingdom	University of Birmingham Institute of Biomedical Research	Birmingham
United Kingdom	Cambridge University Hospitals NHS Foundation Trust - Addenbrooke's Hospital	Cambridge
United Kingdom	Local Institution - 558	Hardwick
United Kingdom	North Tees (DRS) Synexus North Teesside Clinical Research Centre	Hardwick
United Kingdom	Local Institution - 556	Hexham
United Kingdom	Synexus Hexham Clinical Research Centre, Hexham (DRS)	Hexham
United Kingdom	Chelsea and Westminster Hospital NHS Foundation Trust - Chelsea and Westminster Hospital (CWH)	London
United Kingdom	Imperial College University Trust	London
United Kingdom	Kings College Hospital	London
United Kingdom	Local Institution - 559	London
United States	University of Michigan	Ann Arbor	Michigan
United States	Texas Clinical Research Institute LLC	Arlington	Texas
United States	University of Colorado, School of Medicine - Hepatology Clinic - Anschutz	Aurora	Colorado
United States	The Institute for Digestive Health & Liver Disease at Mercy Medical Center	Baltimore	Maryland
United States	Beth Israel Deaconness Medical Center	Boston	Massachusetts
United States	Boston University Medical Center	Boston	Massachusetts
United States	Bridgeport Hospital	Bridgeport	Connecticut
United States	University of Vermont Medical Center Gastro	Burlington	Vermont
United States	Digestive Disease Associates, PA	Catonsville	Maryland
United States	Local Institution - 102	Chapel Hill	North Carolina
United States	UNC Hospitals GI Medicine Clinic	Chapel Hill	North Carolina
United States	ClinSearch LLC	Chattanooga	Tennessee
United States	Rush University Medical Center - University Cardiovascular Surgeons	Chicago	Illinois
United States	University of Chicago Medicine	Chicago	Illinois
United States	Peak Gastroenterology Associates	Colorado Springs	Colorado
United States	Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Liver Institute at Methodist Dallas	Dallas	Texas
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Henry Ford Hospital	Detroit	Michigan
United States	Duke University School of Medicine	Durham	North Carolina
United States	South Denver Gastroenterology	Englewood	Colorado
United States	Brooke Army Medical Center Francis Street Medical Center	Fort Sam Houston	Texas
United States	Gastro One	Germantown	Tennessee
United States	Baylor College of Medicine - Baylor Heart Clinic	Houston	Texas
United States	Houston Methodist Hospital	Houston	Texas
United States	Carolinas HealthCare System Digestive Health	Huntersville	North Carolina
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	UC San Diego School of Medicine	La Jolla	California
United States	Florida Digestive Health Specialists	Lakewood Ranch	Florida
United States	Local Institution - 176	Lakewood Ranch	Florida
United States	Cedars-Sinai Comprehensive Transplant Center	Los Angeles	California
United States	Gastrointestinal Specialists of Georgia, PC	Marietta	Georgia
United States	University of Miami Schiff Center for Liver Diseases	Miami	Florida
United States	Intermountain Medical Center	Murray	Utah
United States	Yale Cancer Center	New Haven	Connecticut
United States	Ochsner Medical Center	New Orleans	Louisiana
United States	Tulane University Health Sciences Center	New Orleans	Louisiana
United States	Beth Israel Medical Center	New York	New York
United States	Concorde Medical Group	New York	New York
United States	New York Presbyterian Hospital - Weill-Cornell	New York	New York
United States	Bon Secours Liver Institute of Hampton Roads	Newport News	Virginia
United States	Digestive and Liver Disease Specialists	Norfolk	Virginia
United States	University of Nebraska	Omaha	Nebraska
United States	IMIC, Inc.	Palmetto Bay	Florida
United States	California Liver Research Institute	Pasadena	California
United States	Mayo Clinic Phoenix	Phoenix	Arizona
United States	Saint Joseph's Hosptial and Medical Center - Barrow Neurological Institute	Phoenix	Arizona
United States	University of Pittsburgh Medical Center - Center for Liver Diseases	Pittsburgh	Pennsylvania
United States	Advanced Medical Research Center	Port Orange	Florida
United States	University Gastroenterology	Providence	Rhode Island
United States	Inland Empire Liver Foundation	Rialto	California
United States	Bon Secours Liver Institute of Richmond	Richmond	Virginia
United States	McGuire Veterans Affairs Medical Center	Richmond	Virginia
United States	Virginia Commonwealth University School of Medicine	Richmond	Virginia
United States	University of Rochester Medical Center	Rochester	New York
United States	Digestive Health Associates of Texas (DHAT)	Rockwell	Texas
United States	University of California Davis Medical Center	Sacramento	California
United States	Saint Louis University School of Medicine	Saint Louis	Missouri
United States	American Research Corporation	San Antonio	Texas
United States	Southern California GI & Liver Centers	San Clemente	California
United States	Liver Institute Northwest PLLC	Seattle	Washington
United States	University of Washington Harborview Medical Center	Seattle	Washington
United States	WestGlen Gastrointestinal Consultants, P.A.	Shawnee Mission	Kansas
United States	Tampa General Hospital	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  Japan,  Korea, Republic of,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Achieve a =1 Stage Improvement in Liver Fibrosis Using the NASH CRN Histological Scoring System at Week 52	Percentage of participants who achieve a =1 stage improvement in liver fibrosis using the NASH CRN Histological Scoring System at Week 52. A participant with a change of = -1 from baseline in fibrosis stage is considered as an improvement responder for this endpoint.; The NASH CRN Histologic Scoring System comprised: steatosis (0 to 3) lobular inflammation (0 to 3) hepatocellular ballooning (0 to 2) fibrosis disease stage (0 to 4); Stage 0 - None; Stage 1a - Mild (delicate) zone 3 perisinusoidal fibrosis; Stage 1b - Moderate (dense) zone 3 perisinusoidal fibrosis; Stage 1c - Portal/periportal fibrosis only; Stage 2 - Zone 3 perisinusoidal fibrosis with portal/periportal fibrosis; Stage 3 - Bridging fibrosis; Stage 4 - Cirrhosis.	From baseline up to week 52
Secondary	Percentage of Participants With no Worsening of Steatohepatitis and =1 Stage Improvement in Liver Fibrosis Score at Week 52	Percentage of participants with no worsening of steatohepatitis and =1 stage improvement in liver fibrosis score at week 52 using the NASH CRN Histological Scoring System at Week 52. A participant with a change of = -1 from baseline in fibrosis stage and no worsening in steatohepatitis is considered as an improvement responder for this endpoint.; The NASH CRN Histologic Scoring System comprised: steatosis (0 to 3) lobular inflammation (0 to 3) hepatocellular ballooning (0 to 2) fibrosis disease stage (0 to 4); Stage 0 - None; Stage 1a - Mild (delicate) zone 3 perisinusoidal fibrosis; Stage 1b - Moderate (dense) zone 3 perisinusoidal fibrosis; Stage 1c - Portal/periportal fibrosis only; Stage 2 - Zone 3 perisinusoidal fibrosis with portal/periportal fibrosis; Stage 3 - Bridging fibrosis; Stage 4 - Cirrhosis.	From baseline up to week 52
Secondary	Percentage of Participants With Improvement in Total NAS	Percentage of participants with an improvement of = 2 points in the total NAS with improvement in more than one category of steatosis, lobular inflammation, and hepatocellular ballooning, and no worsening of liver fibrosis at Week 52. A participant with a change of = -2 from baseline in total NAS, a change of = -1 from baseline in more than one subscore, and a change of = 0 from baseline in fibrosis stage is considered as a responder for this endpoint.	From baseline up to week 52
Secondary	Percentage of Participants With Resolution of NASH	Percentage of participants who demonstrate absence of ballooning, and lobular inflammation score of 0 or 1 at Week 52.; Absence of ballooning is defined as a score of 0 in hepatocellular ballooning. A participant with a score of 0 in ballooning, a score of 0 or 1 in lobular inflammation is considered as a responder for this endpoint.	From baseline up to week 52
Secondary	Percentage of Participants With Resolution of NASH With no Worsening of Liver Fibrosis	Percentage of participants who demonstrate absence of ballooning, and lobular inflammation score of 0 or 1 and no worsening of liver fibrosis at Week 52; Absence of ballooning is defined as a score of 0 in hepatocellular ballooning. Worsening of fibrosis stage was defined as progression of NASH CRN fibrosis stage. A participant with a score of 0 in ballooning, a score of 0 or 1 in lobular inflammation, and a change of = 0 from baseline in fibrosis stage is considered as a responder for this endpoint.	From baseline up to week 52
Secondary	Percentage of Participants Who Progressed to Cirrhosis	Percentage of participants who progressed to cirrhosis	From baseline up to week 52
Secondary	Mean Change From Baseline in Liver Biochemistry	Mean change from Baseline in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and ?-glutamyl transferase (GGT)	From baseline up to week 52
Secondary	Mean Change From Baseline in Metabolic Parameters	Mean change from baseline in total low density cholesterol (LDL) high density cholesterol (HDL), and triglycerides	From baseline up to week 52
Secondary	Cmax	Cmax is defined as maximum plasma concentration of the drug	Day 1 and at Week 4
Secondary	Tmax	Tmax is defined is the time to maximum plasma concentration	Day 1 and at Week 4
Secondary	AUC (0-t)	Area under the plasma concentration time-curve. AUC from time 0 to the last time of quantifiable concentration	Day 1 and at Week 4
Secondary	AUC t	Area under the plasma concentration time-curve. AUC over the dosing interval.	Day 1 and at Week 4
Secondary	Apparent Total Body Clearance of the Drug	Apparent total body clearance of the drug (CL/F)	At Week 4
Secondary	Number of Participants With Treatment Related Safety Events	Number of participants with treatment related safety events	From baseline up to week 52
Secondary	Mean Change From Baseline of ECG Results - PR Intervals	Mean change from baseline in PR interval; PR Interval: Atrial depolarization and conduction through the AV node Normal Range: 0.12 - 0.20 (120 to 200 msec)	From baseline up to week 52
Secondary	Mean Change From Baseline of ECG Results - QRS Duration	Mean change from baseline in QRS duration QRS Duration: Ventricular depolarization and atrial repolarization Normal Range: 0.08 to 0.10 (80 to 100 msec)	From baseline up to week 52
Secondary	Mean Change From Baseline of ECG Results - QT Interval	Mean change from baseline in QT interval; QT Interval: Ventricular depolarization plus ventricular repolarization Normal Range: 400 to 460 msec	From baseline up to week 52
Secondary	Mean Change From Baseline of ECG Results - QTcB Interval	Mean change from baseline in QTcB interval; QT Interval: Ventricular depolarization plus ventricular repolarization Normal Range: 400 to 460 msec; QTc: QT interval corrected based on the patient's heart rate; QTcB: An electrocardiographic finding in which the QT interval corrected for heart rate using Bazzett's formula. QTc = QT/v(RR) RR= Respiration Rate	From baseline up to week 52
Secondary	Mean Change From Baseline of ECG Results - QTcF Interval	Mean change from baseline in QTcF interval; QT Interval: Ventricular depolarization plus ventricular repolarization Normal Range: 400 to 460 msec; QTc: QT interval corrected based on the patient's heart rate; QTcF: An electrocardiographic finding in which the QT interval corrected for heart rate using Fridericia's formula. QTc = QT/?(RR) RR = Respiration rate	From baseline up to week 52

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