Study to Evaluate the Efficacy and Safety of CC-90001 in Participants With Non-alcoholic Steatohepatitis (NASH) and Liver Fibrosis
- Conditions
- Liver CirrhosisNon-alcoholic Fatty Liver Disease
- Interventions
- Drug: Placebo
- Registration Number
- NCT04048876
- Lead Sponsor
- Celgene
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 56
- 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
- Key Exclusion Criteria
- History or evidence of decompensated liver disease,
- Hepatitis and fibrosis more likely related to etiologies other than non-alcoholic steatohepatitis (NASH).
- Participant has urine ethyl glucuronide (EtG) > 500 ng/mL at Screening.
- 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]).
- History of hepatitis B and/or hepatitis C.
- History of malignancy within the last 5 years (exceptions: excised and cured basal/squamous cell skin carcinomas and cervical carcinoma in situ).
- Pregnancy or lactation.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description CC-90001 200 mg once daily CC-90001 CC-90001 200 mg QD Placebo once daily Placebo Placebo QD CC-90001 400 mg once daily (QD) CC-90001 CC-90001 400 mg QD CC-90001 100 mg once daily CC-90001 CC-90001 100 mg QD
- Primary Outcome Measures
Name Time Method Percentage of Participants Who Achieve a ≥1 Stage Improvement in Liver Fibrosis Using the NASH CRN Histological Scoring System at Week 52 From baseline up to 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.
- Secondary Outcome Measures
Name Time Method Mean Change From Baseline of ECG Results - QTcB Interval From baseline up to week 52 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/√(RR) RR= Respiration RatePercentage of Participants With Resolution of NASH From baseline up to week 52 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.Tmax Day 1 and at Week 4 Tmax is defined is the time to maximum plasma concentration
Mean Change From Baseline of ECG Results - PR Intervals From baseline up to week 52 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)Percentage of Participants Who Progressed to Cirrhosis From baseline up to week 52 Percentage of participants who progressed to cirrhosis
Cmax Day 1 and at Week 4 Cmax is defined as maximum plasma concentration of the drug
AUC t Day 1 and at Week 4 Area under the plasma concentration time-curve. AUC over the dosing interval.
Apparent Total Body Clearance of the Drug At Week 4 Apparent total body clearance of the drug (CL/F)
Mean Change From Baseline of ECG Results - QRS Duration From baseline up to week 52 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)
Percentage of Participants With no Worsening of Steatohepatitis and ≥1 Stage Improvement in Liver Fibrosis Score at Week 52 From baseline up to 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.Percentage of Participants With Improvement in Total NAS From baseline up to week 52 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.
Mean Change From Baseline in Liver Biochemistry From baseline up to week 52 Mean change from Baseline in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT)
AUC (0-t) Day 1 and at Week 4 Area under the plasma concentration time-curve. AUC from time 0 to the last time of quantifiable concentration
Number of Participants With Treatment Related Safety Events From baseline up to week 52 Number of participants with treatment related safety events
Mean Change From Baseline of ECG Results - QT Interval From baseline up to week 52 Mean change from baseline in QT interval
QT Interval: Ventricular depolarization plus ventricular repolarization Normal Range: 400 to 460 msecMean Change From Baseline of ECG Results - QTcF Interval From baseline up to week 52 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 ratePercentage of Participants With Resolution of NASH With no Worsening of Liver Fibrosis From baseline up to week 52 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.Mean Change From Baseline in Metabolic Parameters From baseline up to week 52 Mean change from baseline in total low density cholesterol (LDL) high density cholesterol (HDL), and triglycerides
Trial Locations
- Locations (142)
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Digestive Disease Associates, PA
🇺🇸Catonsville, Maryland, United States
Local Institution - 609
🇯🇵Saga, Japan
CHU d'Angers
🇫🇷Angers, France
Hopital Hautepierre
🇫🇷Strasbourg, France
Universitaetsklinikum der RWTH Aachen
🇩🇪Aachen, Germany
Hamamatsu University Hospital
🇯🇵Hamamatsu, Japan
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
University of Calgary, Cumming School of Medicine
🇨🇦Calgary, Alberta, Canada
University of Sydney - Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
Toronto Center for Liver Disease - Francis Family Liver Clinic
🇨🇦Toronto, Ontario, Canada
Assistance Publique - Hopitaux de Paris - Hopital Cochin
🇫🇷Paris, France
Nepean Hospital
🇦🇺Kingswood, New South Wales, Australia
Assistance Publique - Hopitaux de Paris - Hopital Beaujon
🇫🇷Clichy cedex, France
Local Institution - 608
🇯🇵Kashihara, Japan
Local Institution - 607
🇯🇵Kurume, Fukuoka, Japan
Assistance Publique - Hopitaux de Paris - Hopital Universitaire Pitie Salpetriere
🇫🇷Paris CEDEX 13, France
Hopital Haut Leveque
🇫🇷Pessac Cedex, France
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
🇩🇪Mainz, Germany
Royal Brisbane and Women's Hospital
🇦🇺Herston, Queensland, Australia
Virginia Commonwealth University School of Medicine
🇺🇸Richmond, Virginia, United States
Nara Medical University Hospital
🇯🇵Kashihara, Japan
South Edmonton Gastroenterology
🇨🇦Edmonton, Alberta, Canada
Mater Hospital Brisbane
🇦🇺South Brisbane, Queensland, Australia
Hanyang University Seoul Hospital
🇰🇷Seoul, Korea, Republic of
Hopital de la Croix-Rousse
🇫🇷Lyon, France
Centre Hospitalier Universitaire de Rennes - Hopital de Pontchaillou
🇫🇷Rennes cedex 09, France
Local Institution - 601
🇯🇵Kawasaki, Japan
Hospital Val d'Hebron
🇪🇸Barcelona, Spain
Shin-Yurigaoka General Hospital
🇯🇵Kawasaki, Japan
Soon Chun Hyang University Hospital Bucheon
🇰🇷Bucheon-si, Korea, Republic of
Johann Wolfgang Goethe University Hospital
🇩🇪Frankfurt am Main, Germany
Belland General Hospital
🇯🇵Sakai-shi, Japan
Local Institution - 605
🇯🇵Sakai-shi, Japan
Universitaetsklinikum Muenster
🇩🇪Muenster, Germany
University Hospital of Girona Dr. Josep Trueta
🇪🇸Girona, Spain
Local Institution - 615
🇯🇵Kyoto-City, Japan
Local Institution - 613
🇯🇵Ogaki, Japan
University of Birmingham Institute of Biomedical Research
🇬🇧Birmingham, United Kingdom
Local Institution - 556
🇬🇧Hexham, United Kingdom
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Yonsei University Wonju Severance Christian Hospital
🇰🇷Wonju-si, Korea, Republic of
Kings College Hospital
🇬🇧London, United Kingdom
Local Institution - 453
🇵🇱Myslowice, Poland
Synexus SCM Sp. z o.o. Oddz. Warszawa
🇵🇱Warszawa, Poland
Local Institution - 558
🇬🇧Hardwick, United Kingdom
Korea University Hospital at Guro
🇰🇷Seoul, Korea, Republic of
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Chelsea and Westminster Hospital NHS Foundation Trust - Chelsea and Westminster Hospital (CWH)
🇬🇧London, United Kingdom
Local Institution - 600
🇯🇵Yokohama, Kanagawa, Japan
ID Clinic
🇵🇱Myslowice, Poland
Synexus Hexham Clinical Research Centre, Hexham (DRS)
🇬🇧Hexham, United Kingdom
Boramae Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Virgen del Rocio
🇪🇸Sevilla, Spain
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Local Institution - 559
🇬🇧London, United Kingdom
Cambridge University Hospitals NHS Foundation Trust - Addenbrooke's Hospital
🇬🇧Cambridge, United Kingdom
Parc Tauli Hospital Universitari
🇪🇸Sabadell (Barcelona), Spain
North Tees (DRS) Synexus North Teesside Clinical Research Centre
🇬🇧Hardwick, United Kingdom
Imperial College University Trust
🇬🇧London, United Kingdom
Baylor College of Medicine - Baylor Heart Clinic
🇺🇸Houston, Texas, United States
Liver Institute Northwest PLLC
🇺🇸Seattle, Washington, United States
University of Washington Harborview Medical Center
🇺🇸Seattle, Washington, United States
University of Miami Schiff Center for Liver Diseases
🇺🇸Miami, Florida, United States
Ogaki Municipal Hospital
🇯🇵Ogaki, Japan
Osaka University Hospital OUH
🇯🇵Osaka-Fu, Japan
Saga University Hospital
🇯🇵Saga, Japan
Yokohama City University Hospital
🇯🇵Yokohama, Kanagawa, Japan
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
UC San Diego School of Medicine
🇺🇸La Jolla, California, United States
Cedars-Sinai Comprehensive Transplant Center
🇺🇸Los Angeles, California, United States
California Liver Research Institute
🇺🇸Pasadena, California, United States
Inland Empire Liver Foundation
🇺🇸Rialto, California, United States
University of California Davis Medical Center
🇺🇸Sacramento, California, United States
Southern California GI & Liver Centers
🇺🇸San Clemente, California, United States
University of Colorado, School of Medicine - Hepatology Clinic - Anschutz
🇺🇸Aurora, Colorado, United States
Peak Gastroenterology Associates
🇺🇸Colorado Springs, Colorado, United States
South Denver Gastroenterology
🇺🇸Englewood, Colorado, United States
Florida Digestive Health Specialists
🇺🇸Lakewood Ranch, Florida, United States
Local Institution - 176
🇺🇸Lakewood Ranch, Florida, United States
IMIC, Inc.
🇺🇸Palmetto Bay, Florida, United States
Advanced Medical Research Center
🇺🇸Port Orange, Florida, United States
Tampa General Hospital
🇺🇸Tampa, Florida, United States
Mayo Clinic Phoenix
🇺🇸Phoenix, Arizona, United States
American Research Corporation
🇺🇸San Antonio, Texas, United States
Gastrointestinal Specialists of Georgia, PC
🇺🇸Marietta, Georgia, United States
Rush University Medical Center - University Cardiovascular Surgeons
🇺🇸Chicago, Illinois, United States
University of Chicago Medicine
🇺🇸Chicago, Illinois, United States
WestGlen Gastrointestinal Consultants, P.A.
🇺🇸Shawnee Mission, Kansas, United States
Ochsner Medical Center
🇺🇸New Orleans, Louisiana, United States
The Institute for Digestive Health & Liver Disease at Mercy Medical Center
🇺🇸Baltimore, Maryland, United States
Boston University Medical Center
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconness Medical Center
🇺🇸Boston, Massachusetts, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Saint Louis University School of Medicine
🇺🇸Saint Louis, Missouri, 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
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Local Institution - 102
🇺🇸Chapel Hill, North Carolina, United States
Duke University School of Medicine
🇺🇸Durham, North Carolina, United States
Carolinas HealthCare System Digestive Health
🇺🇸Huntersville, North Carolina, United States
Ohio State University Wexner Medical Center
🇺🇸Columbus, Ohio, United States
University of Pittsburgh Medical Center - Center for Liver Diseases
🇺🇸Pittsburgh, Pennsylvania, United States
Gastro One
🇺🇸Germantown, Tennessee, United States
ClinSearch LLC
🇺🇸Chattanooga, Tennessee, United States
Texas Clinical Research Institute LLC
🇺🇸Arlington, Texas, United States
Liver Institute at Methodist Dallas
🇺🇸Dallas, Texas, United States
Brooke Army Medical Center Francis Street Medical Center
🇺🇸Fort Sam Houston, Texas, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
Digestive Health Associates of Texas (DHAT)
🇺🇸Rockwell, Texas, United States
Intermountain Medical Center
🇺🇸Murray, Utah, United States
University of Vermont Medical Center Gastro
🇺🇸Burlington, Vermont, United States
Bon Secours Liver Institute of Hampton Roads
🇺🇸Newport News, Virginia, United States
Bon Secours Liver Institute of Richmond
🇺🇸Richmond, Virginia, United States
McGuire Veterans Affairs Medical Center
🇺🇸Richmond, Virginia, United States
Kurume University Hospital
🇯🇵Kurume, Fukuoka, Japan
Japanese Red Cross Musashino Hospital
🇯🇵Musashino, Japan
Aichi Medical University Hospital
🇯🇵Nagakute, Japan
Local Institution - 602
🇯🇵Musashino, Japan
Local Institution - 612
🇯🇵Suita, Japan
Wojewodzki Specjalistyczny Szpital im. dr Wladyslawa Bieganskiego
🇵🇱Lodz, Poland
Local Institution - 356
🇫🇷Strasbourg, France
Bridgeport Hospital
🇺🇸Bridgeport, Connecticut, United States
University Hospital, Kyoto Prefectural University of Medicine
🇯🇵Kyoto-City, Japan
Tulane University Health Sciences Center
🇺🇸New Orleans, Louisiana, United States
Local Institution - 611
🇯🇵Nagakute, Japan
Local Institution - 604
🇯🇵Hamamatsu, Japan
Local Institution - 603
🇯🇵Osaka-Fu, Japan
Saiseikai Suita Hospital
🇯🇵Suita, Japan
Saint Joseph's Hosptial and Medical Center - Barrow Neurological Institute
🇺🇸Phoenix, Arizona, United States
University of Nebraska
🇺🇸Omaha, Nebraska, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
UNC Hospitals GI Medicine Clinic
🇺🇸Chapel Hill, North Carolina, United States
Digestive and Liver Disease Specialists
🇺🇸Norfolk, Virginia, United States
University Gastroenterology
🇺🇸Providence, Rhode Island, United States
Vancouver General Hospital
🇨🇦Vancouver, British Columbia, Canada