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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT02217475
Registration number
NCT02217475
Ethics application status
Date submitted
13/08/2014
Date registered
15/08/2014
Date last updated
10/05/2019
Titles & IDs
Public title
Efficacy and Safety Study of Cenicriviroc for the Treatment of Nonalcoholic Steatohepatitis (NASH) in Adult Participants With Liver Fibrosis
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Scientific title
CENTAUR: Efficacy and Safety Study of Cenicriviroc for the Treatment of Nonalcoholic Steatohepatitis (NASH) in Adult Subjects With Liver Fibrosis
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Secondary ID [1]
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2016-004754-15
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Secondary ID [2]
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652-2-203
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Universal Trial Number (UTN)
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Trial acronym
CENTAUR
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Nonalcoholic Steatohepatitis
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Condition category
Condition code
Oral and Gastrointestinal
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Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
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Metabolic and Endocrine
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Metabolic disorders
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Diet and Nutrition
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Obesity
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Cenicriviroc
Treatment: Drugs - Placebo
Experimental: Cenicriviroc (CVC) 150mg/CVC 150 mg - CVC 150 mg tablet in Years 1 and 2.
Experimental: Placebo/CVC 150 mg - Placebo-matching CVC tablet in Year 1 then CVC 150 mg tablet in Year 2.
Placebo Comparator: Placebo/Placebo - Placebo-matching cenicriviroc (CVC) tablet in Years 1 and 2.
Treatment: Drugs: Cenicriviroc
CVC 150 mg, administered orally once daily and taken every morning with food.
Treatment: Drugs: Placebo
Placebo administered orally once daily and taken every morning with food.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Number of Participant With Hepatic Histological Improvement in NAS by = 2 Points With at Least 1-Point Reduction in Either Lobular Inflammation or Hepatocellular Ballooning and no Concurrent Worsening of Fibrosis at Year 1
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Assessment method [1]
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Hepatic histological improvement in Nonalcoholic Fatty Liver Disease Activity Score (NAS) at Year 1 was defined as a decrease (improvement) in NAS by = 2 with at least a 1-point reduction in either lobular inflammation or hepatocellular ballooning and with no concurrent worsening of fibrosis stage. The NAS was derived as the unweighted sum of steatosis (0 to 3), lobular inflammation (0 to 3), and hepatocellular ballooning (0 to 2) scores. The NAS ranges from 0-8 with the higher score indicating more aggressive disease. Evaluation of fibrosis stage was based on the nonalcoholic steatohepatitis clinical research network (NASH CRN) fibrosis staging system, which was scaled from 0 to 4 stages where, 0=None to 4=Cirrhosis. Worsening of fibrosis stage was defined as progression of NASH CRN fibrosis stage.
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Timepoint [1]
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Year 1
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Secondary outcome [1]
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Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage and Improvement in Fibrosis by at Least 1 Stage (NASH CRN System) and no Worsening of Steatohepatitis at Year 1
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Assessment method [1]
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Complete resolution of steatohepatitis was defined as histopathologic interpretation of no fatty liver disease, or simple or isolated steatosis with no steatohepatitis. As per NASH CRN system, no worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade. The evaluation of fibrosis stage associated with NASH was based on the NASH CRN fibrosis staging system which was scaled from 0 to 4 stages where, 0=None to 4=Cirrhosis.
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Timepoint [1]
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Year 1
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Secondary outcome [2]
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Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage and Improvement in Fibrosis by at Least 1 Stage (NASH CRN System) and no Worsening of Steatohepatitis at Year 2
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Assessment method [2]
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Complete resolution of steatohepatitis was defined as histopathologic interpretation of no fatty liver disease, or simple or isolated steatosis with no steatohepatitis. As per NASH CRN system, no worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade. The evaluation of fibrosis stage associated with NASH was based on the NASH CRN fibrosis staging system which was scaled from 0 to 4 stages where, 0=None to 4=Cirrhosis.
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Timepoint [2]
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Year 2
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Secondary outcome [3]
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Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage at Year 1
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Assessment method [3]
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Complete resolution of steatohepatitis was defined as histopathologic interpretation of no fatty liver disease, or simple or isolated steatosis with no steatohepatitis. As per NASH CRN system, no worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade. The evaluation of fibrosis stage associated with NASH was based on the NASH CRN fibrosis staging system which was scaled from 0 to 4 stages where, 0=None to 4=Cirrhosis.
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Timepoint [3]
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Year 1
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Secondary outcome [4]
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Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage at Year 2
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Assessment method [4]
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Complete resolution of steatohepatitis was defined as histopathologic interpretation of no fatty liver disease, or simple or isolated steatosis with no steatohepatitis. As per NASH CRN system, no worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade. The evaluation of fibrosis stage associated with NASH was based on the NASH CRN fibrosis staging system which was scaled from 0 to 4 stages where, 0=None to 4=Cirrhosis.
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Timepoint [4]
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Year 2
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Secondary outcome [5]
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Number of Participants With Improvement in Fibrosis by at Least 1 Stage (NASH CRN System) and no Worsening of Steatohepatitis at Year 1
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Assessment method [5]
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The evaluation of fibrosis stage associated with NASH was based on the NASH CRN Fibrosis Staging System which was scaled from 0 to 4 stages where, 0=None to 4=Cirrhosis. As per NASH CRN system, no worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade.
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Timepoint [5]
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Year 1
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Secondary outcome [6]
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Number of Participants With Improvement in Fibrosis by at Least 1 Stage (NASH CRN System) and no Worsening of Steatohepatitis at Year 2
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Assessment method [6]
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The evaluation of fibrosis stage associated with NASH was based on the NASH CRN Fibrosis Staging System which was scaled from 0 to 4 stages where, 0=None to 4=Cirrhosis. As per NASH CRN system, no worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade.
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Timepoint [6]
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Year 2
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Secondary outcome [7]
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Number of Participants With Deaths, Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading Study Drug to Discontinuation
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Assessment method [7]
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A TEAE was defined as any adverse event that started or worsened on or after the start of the study medication and up to 30 days after the discontinuation of the study medication. An SAE was defined as any untoward medical occurrence that, at any dose, results in death, was life threatening, requires hospitalization or results in prolongation of existing hospitalization, results in disability/incapacity, or was a congenital anomaly/birth defect.
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Timepoint [7]
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Years 1 and 2
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Secondary outcome [8]
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Number of Participants With Clinically Significant Changes in Vital Signs
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Assessment method [8]
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Vital signs included blood pressure, temperature, heart rate, and respiration rate. Vital signs were reviewed by the Investigator for clinically significant changes.
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Timepoint [8]
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Years 1 and 2
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Secondary outcome [9]
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Number of Participants With Clinical Laboratory Abnormalities
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Assessment method [9]
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Grade 3-4 abnormal clinical laboratory values that occurred in =2% participants were reported. Criteria used for various parameters was:Fasting glucose Grade3:>250 - 500 mg/dL and Grade4: >500 mg/dL; Alanine aminotransferase(ALT)Grade3:>5.0 - 20.0 ×Upper Limit of Normal(ULN)and Grade4:>20.0 ×ULN; Aspartate aminotransferase(AST)Grade3: >5.0 - 20.0 ×ULN and Grade4: >20.0 ×ULN; Activated partial thromboplastin(APT)/Partial thromboplastin time(PTT)Grade3: >2.5×ULN; Triglycerides Grade3 >500 - 1000 mg/dL and Grade4: >1000 mg/dL; Gamma-glutamyl transferase(GGT)Grade3: >5.0 - 20.0 ×ULN and Grade4: >20.0 ×ULN; Creatine kinase Grade 3: >5.0 - 10.0 ×ULN and Grade4: >10.0 ×ULN; Uric acid Grade3:(ULN - 10 mg/dL; ULN - 0.59 mmol/L) and Grade4: >10 mg/dL; Amylase Grade3: >2.0 - 5.0 ×ULN and Grade4: >5.0 ×ULN; Lipase Grade3: >2.0 - 5.0 xULN and Grade4: >5.0 xULN; Phosphorus Grade3: <2.0 - 1.0 mg/dL and Grade4: <1.0 mg/dL and Absolute neutrophil Grade3: <1.0 - 0.5 × 109/L and Grade4: <0.5 × 109/L.
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Timepoint [9]
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Years 1 and 2
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Secondary outcome [10]
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Number of Participants With Clinically Abnormal in Electrocardiogram (ECG) Findings
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Assessment method [10]
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A 12-lead ECG was performed. ECG results were reviewed by the Investigator for clinically notable abnormalities.
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Timepoint [10]
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Years 1 and 2
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Secondary outcome [11]
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Number of Participants With Hepatic Histological Improvement in NAS at Year 2
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Assessment method [11]
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Hepatic histological improvement in NAS at Year 2 was defined as a decrease (improvement) in NAS by = 2 with at least a 1-point reduction in either lobular inflammation or hepatocellular ballooning and with no concurrent worsening of fibrosis stage. The NAS was derived as the unweighted sum of steatosis (0 to 3), lobular inflammation (0 to 3), and hepatocellular ballooning (0 to 2) scores. The NAS ranges from 0-8 with the higher score indicating more aggressive disease.
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Timepoint [11]
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Year 2
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Secondary outcome [12]
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Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 1
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Assessment method [12]
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NAS was calculated using the following 3 categorical features: steatosis which was scaled from 0-3 (steatosis score is defined as 0= <5%, 1= 5 - 33%, 2= >33 - 66%, and 3= >66%), lobular inflammation which was scaled from 0-3 (lobular inflammation score defined as 0= no foci, 1= < 2 foci/200x, 2= 2-4 foci/200x, and 3= > 4 foci/200x), and hepatocellular ballooning which was scaled from 0-2 (hepatocellular ballooning score is defined as 0=none, 1=few balloon cells, 2=many cells/prominent ballooning). A negative change from Baseline indicates improvement.
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Timepoint [12]
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Year 1
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Secondary outcome [13]
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Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 2
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Assessment method [13]
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NAS was calculated using the following 3 categorical features: steatosis which was scaled from 0-3 (steatosis score is defined as 0= <5%, 1= 5 - 33%, 2= >33 - 66%, and 3= >66%), lobular inflammation which was scaled from 0-3 (lobular inflammation score defined as 0= no foci, 1= < 2 foci/200x, 2= 2-4 foci/200x, and 3= > 4 foci/200x), and hepatocellular ballooning which was scaled from 0-2 (hepatocellular ballooning score is defined as 0=none, 1=few balloon cells, 2=many cells/prominent ballooning). A negative change from Baseline indicates improvement.
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Timepoint [13]
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Year 2
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Secondary outcome [14]
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Number of Participants With Hepatic Histological Improvement With a Minimum 2-Point Improvement in NAS With at Least a 1-Point Improvement in More Than 1 Categorical Features of NAS and no Concurrent Worsening of Fibrosis Stage at Year 1
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Assessment method [14]
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Hepatic histological improvement in NAS was defined as a decrease (improvement) in NAS by = 2 with at least a 1-point reduction in either steatosis, lobular inflammation or hepatocellular ballooning and with no concurrent worsening of fibrosis stage. The NAS was derived as the unweighted sum of steatosis (0 to 3), lobular inflammation (0 to 3), and hepatocellular ballooning (0 to 2) scores. The NAS ranges from 0-8 with the higher score indicating more aggressive disease. Worsening was defined as progression of NASH CRN fibrosis stage.
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Timepoint [14]
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Year 1
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Secondary outcome [15]
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Number of Participants With Hepatic Histological Improvement With a Minimum 2-Point Improvement in NAS With at Least a 1-point Improvement in More Than 1 Categorical Features of NAS and no Concurrent Worsening of Fibrosis Stage at Year 2
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Assessment method [15]
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Hepatic histological improvement in NAS was defined as a decrease (improvement) in NAS by = 2 with at least a 1-point reduction in either steatosis, lobular inflammation or hepatocellular ballooning and with no concurrent worsening of fibrosis stage. The NAS was derived as the unweighted sum of steatosis (0 to 3), lobular inflammation (0 to 3), and hepatocellular ballooning (0 to 2) scores. The NAS ranges from 0-8 with the higher score indicating more aggressive disease. Worsening was defined as progression of NASH CRN fibrosis stage.
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Timepoint [15]
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Year 2
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Secondary outcome [16]
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Number of Participants With Resolution of NASH Using a Modified Definition Based on Categorical Features of NAS and no Concurrent Worsening of Fibrosis Stage at Year 1
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Assessment method [16]
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Resolution of NASH was defined as having no hepatocellular ballooning (grade 0) and minimal to no lobular inflammation (grade 1 or 0) with no concurrent worsening of fibrosis stage (worsening defined as progression of NASH CRN fibrosis stage).
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Timepoint [16]
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Year 1
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Secondary outcome [17]
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Number of Participants With Resolution of NASH Using a Modified Definition Based on Categorical Features of NAS and no Concurrent Worsening of Fibrosis Stage at Year 2
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Assessment method [17]
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Resolution of NASH was defined as having no hepatocellular ballooning (grade 0) and minimal to no lobular inflammation (grade 1 or 0) with no concurrent worsening of fibrosis stage (worsening defined as progression of NASH CRN fibrosis stage).
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Timepoint [17]
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Year 2
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Secondary outcome [18]
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Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 1
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Assessment method [18]
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The morphometric quantitative collagen on liver biopsy was determined as percent collagen area (PCA) using Sirius red stain on liver biopsy at Year 1. A negative change from Baseline indicates improvement.
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Timepoint [18]
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Year 1
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Secondary outcome [19]
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Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 2
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Assessment method [19]
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The morphometric quantitative collagen on liver biopsy was determined as percent collagen area (PCA) using Sirius red stain on liver biopsy at Year 2. A negative change from Baseline indicates improvement.
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Timepoint [19]
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Year 2
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Secondary outcome [20]
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Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (a-SMA) at Year 1
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Assessment method [20]
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The hepatic tissue fibrogenic protein a-SMA level was determined as percent a-SMA + area using a-SMA stain on liver biopsy at Year 1. A positive change from Baseline indicates worsening.
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Timepoint [20]
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Baseline (Day 1) to Year 1
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Secondary outcome [21]
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Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (a-SMA) at Year 2
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Assessment method [21]
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The hepatic tissue fibrogenic protein a-SMA level was determined as percent a-SMA + area using a-SMA stain on liver biopsy at Year 2. A positive change from Baseline indicates worsening.
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Timepoint [21]
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Baseline (Day 1) to Year 2
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Secondary outcome [22]
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Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 1
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Assessment method [22]
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The morphometric quantitative fat content was done to find out the amount of fat accumulated in the liver. A liver biopsy was performed to determine percent fat area, at Year 1. A negative change from Baseline indicates improvement.
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Timepoint [22]
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Year 1
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Secondary outcome [23]
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Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 2
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Assessment method [23]
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The morphometric quantitative fat content was done to find out the amount of fat accumulated in the liver. A liver biopsy was performed to determine percent fat area, at Year 2. A negative change from Baseline indicates improvement.
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Timepoint [23]
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Year 2
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Secondary outcome [24]
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Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 1
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Assessment method [24]
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The participant's histologic fibrosis stage was determined using the NASH CRN system and Ishak scale score assessment at Year 1. The evaluation of fibrosis stage associated with NASH was based on the NASH CRN Fibrosis Staging System which was scaled from 0 to 4 where, 0=None to 4=Cirrhosis. The histologic fibrosis stage based on the Ishak assessment was divided into 1 to 6 stages. Fibrosis was staged with the Ishak scale (ranging from 0=No fibrosis to 6=Cirrhosis). A positive change from Baseline indicates worsening.
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Timepoint [24]
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Baseline (Day 1) to Year 1
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Secondary outcome [25]
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Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 2
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Assessment method [25]
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The participant's histologic fibrosis stage was determined using the NASH CRN system and Ishak scale score assessment at Year 1. The evaluation of fibrosis stage associated with NASH was based on the NASH CRN Fibrosis Staging System which was scaled from 0 to 4 where, 0=None to 4=Cirrhosis. The histologic fibrosis stage based on the Ishak assessment was divided into 1 to 6 stages. Fibrosis was staged with the Ishak scale (ranging from 0=No fibrosis to 6=Cirrhosis). A negative change from Baseline indicates improvement.
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Timepoint [25]
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Baseline (Day 1) to Year 2
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Secondary outcome [26]
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Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 1
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Assessment method [26]
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Portal inflammation on liver biopsy was graded from 0 to 4 where 0= None, 1= Mild, 2= Moderate, and 3= Marked. A positive change from Baseline indicates worsening.
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Timepoint [26]
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Baseline (Day 1) to Year 1
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Secondary outcome [27]
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Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 2
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Assessment method [27]
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Portal inflammation on liver biopsy was graded from 0 to 4 where 0= None, 1= Mild, 2= Moderate, and 3= Marked. A positive change from Baseline indicates worsening.
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Timepoint [27]
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Baseline (Day 1) to Year 2
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Secondary outcome [28]
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Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 3, 6 and 12
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Assessment method [28]
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APRI is the ratio of aspartate aminotransferase (AST) to platelet count. It is calculated using formula, APRI = (AST level [/ULN] / platelet counts [10^9/L]) * 100. An APRI index of <=0.50 indicated the absence of significant fibrosis and an index of > 1.50 indicated the presence of significant fibrosis. A negative change from Baseline indicates decreased fibrosis.
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Timepoint [28]
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Baseline (Month 0) to Months 3, 6 and 12
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Secondary outcome [29]
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Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 15, 18 and 24
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Assessment method [29]
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APRI is the ratio of aspartate aminotransferase (AST) to platelet count. It is calculated using formula, APRI = (AST level [/ULN] / platelet counts [10^9/L]) * 100. An APRI index of <=0.50 indicated the absence of significant fibrosis and an index of > 1.50 indicated the presence of significant fibrosis. A negative change from Baseline indicates decreased fibrosis.
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Timepoint [29]
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Baseline (Month 0) to Months 15, 18 and 24
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Secondary outcome [30]
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Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 3, 6 and 12
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Assessment method [30]
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Fibrosis-4 is the ratio of age in years and aminotransferase to platelet count. It is a non-invasive hepatic fibrosis index score combining standard biochemical values, platelets, alanine aminotransferase (ALT), AST and age that is calculated using formula: FIB-4 = (Age [years] x AST [U/L]) / (platelets [10^9/L] x (square root of ALT [U/L])). A FIB-4 index of < 1.45 indicated no or moderate fibrosis and an index of > 3.25 indicated extensive fibrosis/cirrhosis. A positive change from Baseline indicates increased fibrosis.
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Timepoint [30]
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0
Baseline (Month 0) to Months 3, 6 and 12
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Secondary outcome [31]
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Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 15, 18 and 24
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Assessment method [31]
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Fibrosis-4 is the ratio of age in years and aminotransferase to platelet count. It is a non-invasive hepatic fibrosis index score combining standard biochemical values, platelets, alanine aminotransferase (ALT), AST and age that is calculated using formula: FIB-4 = (Age [years] x AST [U/L]) / (platelets [10^9/L] x (square root of ALT [U/L])). A FIB-4 index of < 1.45 indicated no or moderate fibrosis and an index of > 3.25 indicated extensive fibrosis/cirrhosis. A positive change from Baseline indicates increased fibrosis.
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Timepoint [31]
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Baseline (Month 0) to Months 15, 18 and 24
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Secondary outcome [32]
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Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 6 and 12
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Assessment method [32]
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Hyaluronic acid is a non-invasive hepatic fibrosis marker. A negative change from Baseline indicates decreased fibrosis.
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Timepoint [32]
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Baseline (Month 0) to Months 6 and 12
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Secondary outcome [33]
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Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 18 and 24
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Assessment method [33]
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Hyaluronic acid is a non-invasive hepatic fibrosis marker. A positive change from Baseline indicates increased fibrosis.
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Timepoint [33]
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Baseline (Month 0) to Months 18 and 24
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Secondary outcome [34]
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Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Nonalcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) at Months 3, 6 and 12
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Assessment method [34]
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NFS is calculated using formula: NFS = -1.675 + 0.037 * age (years) + 0.094 * Body mass index (BMI) (kg/m^2) + 1.13 * Impaired fasting glucose (IFG)/diabetes (yes = 1, no = 0) + 0.99 * Aspartate aminotransferase (AST)/ Alanine aminotransferase (ALT) ratio - 0.013 × platelet (*10^9/L) - 0.66 * albumin (g/dL). A negative change from Baseline indicates decreased fibrosis.
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Timepoint [34]
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0
Baseline (Month 0) to Months 3, 6 and 12
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Secondary outcome [35]
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Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: NAFLD Fibrosis Score (NFS) at Months 15, 18 and 24
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Assessment method [35]
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NFS is calculated using formula: NFS = -1.675 + 0.037 * age (years) + 0.094 * Body mass index (BMI) (kg/m^2) + 1.13 * Impaired fasting glucose (IFG)/diabetes (yes = 1, no = 0) + 0.99 * Aspartate aminotransferase (AST)/ Alanine aminotransferase (ALT) ratio - 0.013 × platelet (*10^9/L) - 0.66 * albumin (g/dL). A negative change from Baseline indicates decreased fibrosis.
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Timepoint [35]
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0
Baseline (Month 0) to Months 15, 18 and 24
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Secondary outcome [36]
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Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 6 and 12
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Assessment method [36]
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The markers of fibrosis assessed in this test comprised hyaluronic acid (CHA), tissue inhibitor of metalloproteinase (CTIMP1) and procollagen III N-terminal peptide (CP3NP); these are components of the extracellular matrix and basement sinusoidal membrane of the liver and are elevated during activation of the stellate cell. The ELF tests were performed on Centaur device and the composite score was calculated as follows: ELF score = 2.278 + 0.851 ln(CHA) + 0.751 ln (CP3NP) + 0.394 ln(CTIMP1). ELF score < 7.7: no to mild fibrosis; = 7.7 - < 9.8: Moderate fibrosis; = 9.8 - < 11.3: Severe fibrosis; = 11.3: Cirrhosis. A negative change from Baseline indicates decreased fibrosis.
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Timepoint [36]
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0
Baseline (Month 0) to Months 6 and 12
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Secondary outcome [37]
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Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 18 and 24
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Assessment method [37]
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The markers of fibrosis assessed in this test comprised hyaluronic acid (CHA), tissue inhibitor of metalloproteinase (CTIMP1) and procollagen III N-terminal peptide (CP3NP); these are components of the extracellular matrix and basement sinusoidal membrane of the liver and are elevated during activation of the stellate cell. The ELF tests were performed on Centaur device and the composite score was calculated as follows: ELF score = 2.278 + 0.851 ln(CHA) + 0.751 ln (CP3NP) + 0.394 ln(CTIMP1). ELF score < 7.7: no to mild fibrosis; = 7.7 - < 9.8: Moderate fibrosis; = 9.8 - < 11.3: Severe fibrosis; = 11.3: Cirrhosis. A negative change from Baseline indicates decreased fibrosis.
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Timepoint [37]
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0
Baseline (Month 0) to Months 18 and 24
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Secondary outcome [38]
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Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 3, 6 and 12
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Assessment method [38]
0
0
Caspase-cleaved cytokeratin levels (CK18M30) and total M-65 (CK-18 [M-65]) were measured as biomarkers of hepatocyte apoptosis. A negative change from Baseline indicates decreased hepatocyte apoptosis.
Query!
Timepoint [38]
0
0
Baseline (Month 0) to Months 3, 6 and 12
Query!
Secondary outcome [39]
0
0
Change From Baseline in Biomarkers of Hepatocyte Apoptosis: Caspase Cleaved (CK-18 [M-30]) Levels and Total M-65 (CK-18 [M-65]) Levels at Months 15, 18 and 24
Query!
Assessment method [39]
0
0
Caspase-cleaved cytokeratin levels (CK18M30) and total M-65 (CK-18 [M-65]) were measured as biomarkers of hepatocyte apoptosis. A negative change from Baseline indicates decreased hepatocyte apoptosis.
Query!
Timepoint [39]
0
0
Baseline (Month 0) to Months 15, 18 and 24
Query!
Secondary outcome [40]
0
0
Change From Baseline in Weight at Months 3, 6 and 12
Query!
Assessment method [40]
0
0
A negative change from Baseline represents decreased weight.
Query!
Timepoint [40]
0
0
Baseline (Day 1) to Months 3, 6 and 12
Query!
Secondary outcome [41]
0
0
Change From Baseline in Weight at Months 15, 18 and 24
Query!
Assessment method [41]
0
0
A negative change from Baseline represents decreased weight.
Query!
Timepoint [41]
0
0
Baseline (Day 1) to Months 15, 18 and 24
Query!
Secondary outcome [42]
0
0
Change From Baseline in Body Mass Index (BMI) at Months 3, 6 and 12
Query!
Assessment method [42]
0
0
The body mass index is a value derived from the mass (weight in kgs) and height (in centimeters) of an individual and is calculated as the body mass divided by the square of the body height. A negative change from Baseline represents decreased BMI.
Query!
Timepoint [42]
0
0
Baseline (Day 1) to Months 3, 6 and 12
Query!
Secondary outcome [43]
0
0
Change From Baseline in Body Mass Index (BMI) at Months 15, 18 and 24
Query!
Assessment method [43]
0
0
The body mass index is a value derived from the mass (weight in kgs) and height (in centimeters) of an individual and is calculated as the body mass divided by the square of the body height. A negative change from Baseline represents decreased BMI.
Query!
Timepoint [43]
0
0
Baseline (Day 1) to Months 15, 18 and 24
Query!
Secondary outcome [44]
0
0
Change From Baseline in Waist Circumference at Months 3, 6 and 12
Query!
Assessment method [44]
0
0
A negative change from Baseline represents decreased in waist circumference.
Query!
Timepoint [44]
0
0
Baseline (Day 1) to Months 3, 6 and 12
Query!
Secondary outcome [45]
0
0
Change From Baseline in Waist Circumference at Months 15, 18 and 24
Query!
Assessment method [45]
0
0
A negative change from Baseline represents decreased in waist circumference.
Query!
Timepoint [45]
0
0
Baseline (Day 1) to Months 15, 18 and 24
Query!
Secondary outcome [46]
0
0
Change From Baseline in Hip Circumference at Months 3, 6 and 12
Query!
Assessment method [46]
0
0
A negative change from Baseline represents decreased hip circumference.
Query!
Timepoint [46]
0
0
Baseline (Day 1) to Months 3, 6 and 12
Query!
Secondary outcome [47]
0
0
Change From Baseline in Hip Circumference at Months 15, 18 and 24
Query!
Assessment method [47]
0
0
A negative change from Baseline represents decreased hip circumference.
Query!
Timepoint [47]
0
0
Baseline (Day 1) to Months 15, 18 and 24
Query!
Secondary outcome [48]
0
0
Change From Baseline in Forearm Circumference at Months 3, 6 and 12
Query!
Assessment method [48]
0
0
A negative change from Baseline represents decreased forearm circumference.
Query!
Timepoint [48]
0
0
Baseline (Day 1) to Months 3, 6 and 12
Query!
Secondary outcome [49]
0
0
Change From Baseline in Forearm Circumference at Months 15, 18 and 24
Query!
Assessment method [49]
0
0
A negative change from Baseline represents decreased forearm circumference.
Query!
Timepoint [49]
0
0
Baseline (Day 1) to Months 15, 18 and 24
Query!
Secondary outcome [50]
0
0
Change From Baseline in Tricep Skinfold Thickness at Months 3, 6 and 12
Query!
Assessment method [50]
0
0
A negative change from Baseline represents decreased Tricep Skinfold Thickness.
Query!
Timepoint [50]
0
0
Baseline (Day 1) to Months 3, 6 and 12
Query!
Secondary outcome [51]
0
0
Change From Baseline in Tricep Skinfold Thickness at Months 15, 18 and 24
Query!
Assessment method [51]
0
0
A negative change from Baseline represents decreased Tricep Skinfold Thickness.
Query!
Timepoint [51]
0
0
Baseline (Day 1) to Months 15, 18 and 24
Query!
Eligibility
Key inclusion criteria
- Adult participants aged between 18-75
- Histological evidence of NASH, based on biopsy, with a Nonalcoholic fatty liver
disease Activity Score (NAS) of >= 4 with at least 1 in each component of NAS
- Histological evidence of liver fibrosis defined as NASH Clinical Research Network
(CRN) System Stage 1 to 3
- Meeting any of the 3 major criteria (a, b, c):
1. Documented evidence of type 2 diabetes mellitus
2. High body mass index (> 25 kg/m^2) with at least one of the following criteria of
metabolic syndrome, as defined by the National Cholesterol Education Program:
- Central obesity: waist circumference = 102 cm or 40 inches (male), = 88 cm
or 35 inches (female)
- Dyslipidemia: Triglycerides = 1.7 mmol/L (150 mg/dL)
- Dyslipidemia: High-density lipoprotein (HDL)-cholesterol < 40 mg/dL (male),
< 50 mg/dL (female)
- Blood pressure = 130/85 mmHg (or currently being treated for hypertension)
- Fasting plasma glucose = 6.1 mmol/L (110 mg/dL)
3. Bridging fibrosis (NASH CRN Stage 3) and/or definite NASH (NAS = 5)
- Agree to have one liver biopsy at Screening, one at Year 1, and one at the end of
study treatment (Year 2)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 5 × upper limit
of normal (ULN)
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
75
Years
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
- Hepatitis B surface Antigen (HBsAg) positive
- Hepatitis C antibody (HCVAb) positive with the following 2 exceptions:
1. Participants previously treated for viral hepatitis C with at least a 1-year
period since documented sustained virologic response at Week 12 (post-treatment)
may be eligible if all other eligibility criteria are met
2. Participants with presence of hepatitis C antibody but negative hepatitis C virus
ribonucleic acid RNA without treatment (i.e., spontaneous clearance) may be
eligible if all other eligibility criteria are met
- Prior or planned liver transplantation
- Other known causes of chronic liver disease, including alcoholic liver disease
- History of cirrhosis and/or hepatic decompensation including ascites, hepatic
encephalopathy or variceal bleeding
- Alcohol consumption greater than 21 units/week for males or 14 units/week for females
(one unit of alcohol is ½ pint of beer [285 mL], 1 glass of spirits [25 mL] or 1 glass
of wine [125 mL])
- Human immunodeficiency virus (HIV)-1 or HIV-2 infection
- Weight reduction through bariatric surgery in the past 5 years or planned during the
conduct of the study (including gastric banding)
- Females who are pregnant or breastfeeding
- Any other clinically significant disorders or prior therapy that, in the opinion of
the investigator, would make the participant unsuitable for the study or unable to
comply with the dosing and protocol requirements.
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Blinded (masking used)
Query!
Who is / are masked / blinded?
The people receiving the treatment/s
The people assessing the outcomes
The people analysing the results/data
Query!
Query!
Query!
Query!
Intervention assignment
Crossover
Query!
Other design features
Query!
Phase
Phase 2
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Completed
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
18/09/2014
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
22/06/2017
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
289
Query!
Recruitment in Australia
Recruitment state(s)
ACT,QLD,SA,VIC,WA
Query!
Recruitment hospital [1]
0
0
- Garran
Query!
Recruitment hospital [2]
0
0
- Herston
Query!
Recruitment hospital [3]
0
0
- Adelaide
Query!
Recruitment hospital [4]
0
0
- Bedford Park
Query!
Recruitment hospital [5]
0
0
- Clayton
Query!
Recruitment hospital [6]
0
0
- Heidelberg
Query!
Recruitment hospital [7]
0
0
- Melbourne
Query!
Recruitment hospital [8]
0
0
- Perth
Query!
Recruitment postcode(s) [1]
0
0
2605 - Garran
Query!
Recruitment postcode(s) [2]
0
0
4029 - Herston
Query!
Recruitment postcode(s) [3]
0
0
5000 - Adelaide
Query!
Recruitment postcode(s) [4]
0
0
5042 - Bedford Park
Query!
Recruitment postcode(s) [5]
0
0
3168 - Clayton
Query!
Recruitment postcode(s) [6]
0
0
3084 - Heidelberg
Query!
Recruitment postcode(s) [7]
0
0
3004 - Melbourne
Query!
Recruitment postcode(s) [8]
0
0
6000 - Perth
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
Alabama
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
Arizona
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
California
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Colorado
Query!
Country [5]
0
0
United States of America
Query!
State/province [5]
0
0
Florida
Query!
Country [6]
0
0
United States of America
Query!
State/province [6]
0
0
Illinois
Query!
Country [7]
0
0
United States of America
Query!
State/province [7]
0
0
Kentucky
Query!
Country [8]
0
0
United States of America
Query!
State/province [8]
0
0
Louisiana
Query!
Country [9]
0
0
United States of America
Query!
State/province [9]
0
0
Maryland
Query!
Country [10]
0
0
United States of America
Query!
State/province [10]
0
0
Massachusetts
Query!
Country [11]
0
0
United States of America
Query!
State/province [11]
0
0
Michigan
Query!
Country [12]
0
0
United States of America
Query!
State/province [12]
0
0
Minnesota
Query!
Country [13]
0
0
United States of America
Query!
State/province [13]
0
0
Mississippi
Query!
Country [14]
0
0
United States of America
Query!
State/province [14]
0
0
New York
Query!
Country [15]
0
0
United States of America
Query!
State/province [15]
0
0
North Carolina
Query!
Country [16]
0
0
United States of America
Query!
State/province [16]
0
0
Ohio
Query!
Country [17]
0
0
United States of America
Query!
State/province [17]
0
0
Tennessee
Query!
Country [18]
0
0
United States of America
Query!
State/province [18]
0
0
Texas
Query!
Country [19]
0
0
United States of America
Query!
State/province [19]
0
0
Utah
Query!
Country [20]
0
0
United States of America
Query!
State/province [20]
0
0
Virginia
Query!
Country [21]
0
0
United States of America
Query!
State/province [21]
0
0
Washington
Query!
Country [22]
0
0
Belgium
Query!
State/province [22]
0
0
Brussels
Query!
Country [23]
0
0
Belgium
Query!
State/province [23]
0
0
Edegem
Query!
Country [24]
0
0
Belgium
Query!
State/province [24]
0
0
Leuven
Query!
Country [25]
0
0
France
Query!
State/province [25]
0
0
Angers
Query!
Country [26]
0
0
France
Query!
State/province [26]
0
0
Lyon cedex 04
Query!
Country [27]
0
0
France
Query!
State/province [27]
0
0
Montpellier Cedex 5
Query!
Country [28]
0
0
France
Query!
State/province [28]
0
0
Paris
Query!
Country [29]
0
0
France
Query!
State/province [29]
0
0
Pessac Cedex
Query!
Country [30]
0
0
France
Query!
State/province [30]
0
0
Toulouse
Query!
Country [31]
0
0
France
Query!
State/province [31]
0
0
Vandoeuvre-les Nancy
Query!
Country [32]
0
0
France
Query!
State/province [32]
0
0
Villejuif
Query!
Country [33]
0
0
Germany
Query!
State/province [33]
0
0
BW
Query!
Country [34]
0
0
Germany
Query!
State/province [34]
0
0
HE
Query!
Country [35]
0
0
Germany
Query!
State/province [35]
0
0
HH
Query!
Country [36]
0
0
Germany
Query!
State/province [36]
0
0
Niedersachsen
Query!
Country [37]
0
0
Germany
Query!
State/province [37]
0
0
NRW
Query!
Country [38]
0
0
Germany
Query!
State/province [38]
0
0
Sachsen
Query!
Country [39]
0
0
Germany
Query!
State/province [39]
0
0
SN
Query!
Country [40]
0
0
Germany
Query!
State/province [40]
0
0
VIC
Query!
Country [41]
0
0
Germany
Query!
State/province [41]
0
0
Berlin
Query!
Country [42]
0
0
Germany
Query!
State/province [42]
0
0
Lubeck
Query!
Country [43]
0
0
Hong Kong
Query!
State/province [43]
0
0
New Territories
Query!
Country [44]
0
0
Italy
Query!
State/province [44]
0
0
BO
Query!
Country [45]
0
0
Italy
Query!
State/province [45]
0
0
MI
Query!
Country [46]
0
0
Italy
Query!
State/province [46]
0
0
PA
Query!
Country [47]
0
0
Poland
Query!
State/province [47]
0
0
Chorzow
Query!
Country [48]
0
0
Poland
Query!
State/province [48]
0
0
Lodz
Query!
Country [49]
0
0
Poland
Query!
State/province [49]
0
0
Myslowice
Query!
Country [50]
0
0
Poland
Query!
State/province [50]
0
0
Rzeszow
Query!
Country [51]
0
0
Poland
Query!
State/province [51]
0
0
Wroclaw
Query!
Country [52]
0
0
Spain
Query!
State/province [52]
0
0
Alicante
Query!
Country [53]
0
0
Spain
Query!
State/province [53]
0
0
Barcelona
Query!
Country [54]
0
0
Spain
Query!
State/province [54]
0
0
Madrid
Query!
Country [55]
0
0
United Kingdom
Query!
State/province [55]
0
0
Hampshire
Query!
Country [56]
0
0
United Kingdom
Query!
State/province [56]
0
0
London
Query!
Country [57]
0
0
United Kingdom
Query!
State/province [57]
0
0
Newcastle
Query!
Country [58]
0
0
United Kingdom
Query!
State/province [58]
0
0
Nottingham
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Query!
Name
Tobira Therapeutics, Inc.
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
The purpose of this study is to determine whether cenicriviroc is effective and safe in the
treatment of nonalcoholic steatohepatitis (NASH) in adult participants with liver fibrosis.
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT02217475
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Eric Lefebvre, MD
Query!
Address
0
0
Allergan
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT02217475
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