Back to results

Efficacy and Safety Study of Cenicriviroc for the Treatment of Nonalcoholic Steatohepatitis (NASH) in Adult Participants With Liver Fibrosis (CENTAUR)

Primary Purpose

Nonalcoholic Steatohepatitis

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Cenicriviroc

Placebo

About this trial

This is an interventional treatment trial for Nonalcoholic Steatohepatitis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Cenicriviroc (CVC) 150mg/CVC 150 mg

Placebo/CVC 150 mg

Placebo/Placebo

Arm Description

CVC 150 mg tablet in Years 1 and 2.

Placebo-matching CVC tablet in Year 1 then CVC 150 mg tablet in Year 2.

Placebo-matching cenicriviroc (CVC) tablet in Years 1 and 2.

Outcomes

Primary Outcome Measures

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

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.

Secondary Outcome Measures

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

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.

Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage at Year 1

Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage at Year 2

Number of Participants With Improvement in Fibrosis by at Least 1 Stage (NASH CRN System) and no Worsening of Steatohepatitis 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 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.

Number of Participants With Improvement in Fibrosis by at Least 1 Stage (NASH CRN System) and no Worsening of Steatohepatitis at Year 2

Number of Participants With Deaths, Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading Study Drug to Discontinuation

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.

Number of Participants With Clinically Significant Changes in Vital Signs

Vital signs included blood pressure, temperature, heart rate, and respiration rate. Vital signs were reviewed by the Investigator for clinically significant changes.

Number of Participants With Clinical Laboratory Abnormalities

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.

Number of Participants With Clinically Abnormal in Electrocardiogram (ECG) Findings

A 12-lead ECG was performed. ECG results were reviewed by the Investigator for clinically notable abnormalities.

Number of Participants With Hepatic Histological Improvement in NAS at Year 2

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.

Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 1

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.

Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 2

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

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.

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

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

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).

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

Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 1

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.

Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 2

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.

Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (α-SMA) at Year 1

The hepatic tissue fibrogenic protein α-SMA level was determined as percent α-SMA + area using α-SMA stain on liver biopsy at Year 1. A positive change from Baseline indicates worsening.

Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (α-SMA) at Year 2

The hepatic tissue fibrogenic protein α-SMA level was determined as percent α-SMA + area using α-SMA stain on liver biopsy at Year 2. A positive change from Baseline indicates worsening.

Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 1

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.

Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 2

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.

Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 1

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.

Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 2

Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 1

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.

Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 2

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.

Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 3, 6 and 12

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.

Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 15, 18 and 24

Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 3, 6 and 12

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.

Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 15, 18 and 24

Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 6 and 12

Hyaluronic acid is a non-invasive hepatic fibrosis marker. A negative change from Baseline indicates decreased fibrosis.

Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 18 and 24

Hyaluronic acid is a non-invasive hepatic fibrosis marker. A positive change from Baseline indicates increased fibrosis.

Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Nonalcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) at Months 3, 6 and 12

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.

Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: NAFLD Fibrosis Score (NFS) at Months 15, 18 and 24

Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 6 and 12

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.

Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 18 and 24

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

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.

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

Change From Baseline in Weight at Months 3, 6 and 12

A negative change from Baseline represents decreased weight.

Change From Baseline in Weight at Months 15, 18 and 24

A negative change from Baseline represents decreased weight.

Change From Baseline in Body Mass Index (BMI) at Months 3, 6 and 12

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.

Change From Baseline in Body Mass Index (BMI) at Months 15, 18 and 24

Change From Baseline in Waist Circumference at Months 3, 6 and 12

A negative change from Baseline represents decreased in waist circumference.

Change From Baseline in Waist Circumference at Months 15, 18 and 24

A negative change from Baseline represents decreased in waist circumference.

Change From Baseline in Hip Circumference at Months 3, 6 and 12

A negative change from Baseline represents decreased hip circumference.

Change From Baseline in Hip Circumference at Months 15, 18 and 24

A negative change from Baseline represents decreased hip circumference.

Change From Baseline in Forearm Circumference at Months 3, 6 and 12

A negative change from Baseline represents decreased forearm circumference.

Change From Baseline in Forearm Circumference at Months 15, 18 and 24

A negative change from Baseline represents decreased forearm circumference.

Change From Baseline in Tricep Skinfold Thickness at Months 3, 6 and 12

A negative change from Baseline represents decreased Tricep Skinfold Thickness.

Change From Baseline in Tricep Skinfold Thickness at Months 15, 18 and 24

A negative change from Baseline represents decreased Tricep Skinfold Thickness.

Full Information

NCT ID

NCT02217475

First Posted

August 13, 2014

Last Updated

April 19, 2019

Sponsor

Tobira Therapeutics, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT02217475

Brief Title

Efficacy and Safety Study of Cenicriviroc for the Treatment of Nonalcoholic Steatohepatitis (NASH) in Adult Participants With Liver Fibrosis

Acronym

CENTAUR

Official Title

CENTAUR: Efficacy and Safety Study of Cenicriviroc for the Treatment of Nonalcoholic Steatohepatitis (NASH) in Adult Subjects With Liver Fibrosis

Study Type

Interventional

2. Study Status

Record Verification Date

March 2019

Overall Recruitment Status

Completed

Study Start Date

September 18, 2014 (Actual)

Primary Completion Date

June 30, 2016 (Actual)

Study Completion Date

June 22, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Tobira Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Nonalcoholic Steatohepatitis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

289 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cenicriviroc (CVC) 150mg/CVC 150 mg

Arm Type

Experimental

Arm Description

CVC 150 mg tablet in Years 1 and 2.

Arm Title

Placebo/CVC 150 mg

Arm Type

Experimental

Arm Description

Placebo-matching CVC tablet in Year 1 then CVC 150 mg tablet in Year 2.

Arm Title

Placebo/Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo-matching cenicriviroc (CVC) tablet in Years 1 and 2.

Intervention Type

Drug

Intervention Name(s)

Cenicriviroc

Other Intervention Name(s)

TBR-652

Intervention Description

CVC 150 mg, administered orally once daily and taken every morning with food.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo administered orally once daily and taken every morning with food.

Primary Outcome Measure Information:

Title

Description

Time Frame

Year 1

Secondary Outcome Measure Information:

Title

Description

Time Frame

Year 1

Title

Description

Time Frame

Year 2

Title

Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage at Year 1

Description

Time Frame

Year 1

Title

Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage at Year 2

Description

Time Frame

Year 2

Title

Number of Participants With Improvement in Fibrosis by at Least 1 Stage (NASH CRN System) and no Worsening of Steatohepatitis at Year 1

Description

Time Frame

Year 1

Title

Number of Participants With Improvement in Fibrosis by at Least 1 Stage (NASH CRN System) and no Worsening of Steatohepatitis at Year 2

Description

Time Frame

Year 2

Title

Number of Participants With Deaths, Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading Study Drug to Discontinuation

Description

Time Frame

Years 1 and 2

Title

Number of Participants With Clinically Significant Changes in Vital Signs

Description

Vital signs included blood pressure, temperature, heart rate, and respiration rate. Vital signs were reviewed by the Investigator for clinically significant changes.

Time Frame

Years 1 and 2

Title

Number of Participants With Clinical Laboratory Abnormalities

Description

Time Frame

Years 1 and 2

Title

Number of Participants With Clinically Abnormal in Electrocardiogram (ECG) Findings

Description

A 12-lead ECG was performed. ECG results were reviewed by the Investigator for clinically notable abnormalities.

Time Frame

Years 1 and 2

Title

Number of Participants With Hepatic Histological Improvement in NAS at Year 2

Description

Time Frame

Year 2

Title

Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 1

Description

Time Frame

Year 1

Title

Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 2

Description

Time Frame

Year 2

Title

Description

Time Frame

Year 1

Title

Description

Time Frame

Year 2

Title

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

Description

Time Frame

Year 1

Title

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

Description

Time Frame

Year 2

Title

Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 1

Description

Time Frame

Year 1

Title

Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 2

Description

Time Frame

Year 2

Title

Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (α-SMA) at Year 1

Description

The hepatic tissue fibrogenic protein α-SMA level was determined as percent α-SMA + area using α-SMA stain on liver biopsy at Year 1. A positive change from Baseline indicates worsening.

Time Frame

Baseline (Day 1) to Year 1

Title

Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (α-SMA) at Year 2

Description

The hepatic tissue fibrogenic protein α-SMA level was determined as percent α-SMA + area using α-SMA stain on liver biopsy at Year 2. A positive change from Baseline indicates worsening.

Time Frame

Baseline (Day 1) to Year 2

Title

Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 1

Description

Time Frame

Year 1

Title

Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 2

Description

Time Frame

Year 2

Title

Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 1

Description

Time Frame

Baseline (Day 1) to Year 1

Title

Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 2

Description

Time Frame

Baseline (Day 1) to Year 2

Title

Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 1

Description

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.

Time Frame

Baseline (Day 1) to Year 1

Title

Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 2

Description

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.

Time Frame

Baseline (Day 1) to Year 2

Title

Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 3, 6 and 12

Description

Time Frame

Baseline (Month 0) to Months 3, 6 and 12

Title

Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 15, 18 and 24

Description

Time Frame

Baseline (Month 0) to Months 15, 18 and 24

Title

Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 3, 6 and 12

Description

Time Frame

Baseline (Month 0) to Months 3, 6 and 12

Title

Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 15, 18 and 24

Description

Time Frame

Baseline (Month 0) to Months 15, 18 and 24

Title

Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 6 and 12

Description

Hyaluronic acid is a non-invasive hepatic fibrosis marker. A negative change from Baseline indicates decreased fibrosis.

Time Frame

Baseline (Month 0) to Months 6 and 12

Title

Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 18 and 24

Description

Hyaluronic acid is a non-invasive hepatic fibrosis marker. A positive change from Baseline indicates increased fibrosis.

Time Frame

Baseline (Month 0) to Months 18 and 24

Title

Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Nonalcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) at Months 3, 6 and 12

Description

Time Frame

Baseline (Month 0) to Months 3, 6 and 12

Title

Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: NAFLD Fibrosis Score (NFS) at Months 15, 18 and 24

Description

Time Frame

Baseline (Month 0) to Months 15, 18 and 24

Title

Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 6 and 12

Description

Time Frame

Baseline (Month 0) to Months 6 and 12

Title

Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 18 and 24

Description

Time Frame

Baseline (Month 0) to Months 18 and 24

Title

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

Description

Time Frame

Baseline (Month 0) to Months 3, 6 and 12

Title

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

Description

Time Frame

Baseline (Month 0) to Months 15, 18 and 24

Title

Change From Baseline in Weight at Months 3, 6 and 12

Description

A negative change from Baseline represents decreased weight.

Time Frame

Baseline (Day 1) to Months 3, 6 and 12

Title

Change From Baseline in Weight at Months 15, 18 and 24

Description

A negative change from Baseline represents decreased weight.

Time Frame

Baseline (Day 1) to Months 15, 18 and 24

Title

Change From Baseline in Body Mass Index (BMI) at Months 3, 6 and 12

Description

Time Frame

Baseline (Day 1) to Months 3, 6 and 12

Title

Change From Baseline in Body Mass Index (BMI) at Months 15, 18 and 24

Description

Time Frame

Baseline (Day 1) to Months 15, 18 and 24

Title

Change From Baseline in Waist Circumference at Months 3, 6 and 12

Description

A negative change from Baseline represents decreased in waist circumference.

Time Frame

Baseline (Day 1) to Months 3, 6 and 12

Title

Change From Baseline in Waist Circumference at Months 15, 18 and 24

Description

A negative change from Baseline represents decreased in waist circumference.

Time Frame

Baseline (Day 1) to Months 15, 18 and 24

Title

Change From Baseline in Hip Circumference at Months 3, 6 and 12

Description

A negative change from Baseline represents decreased hip circumference.

Time Frame

Baseline (Day 1) to Months 3, 6 and 12

Title

Change From Baseline in Hip Circumference at Months 15, 18 and 24

Description

A negative change from Baseline represents decreased hip circumference.

Time Frame

Baseline (Day 1) to Months 15, 18 and 24

Title

Change From Baseline in Forearm Circumference at Months 3, 6 and 12

Description

A negative change from Baseline represents decreased forearm circumference.

Time Frame

Baseline (Day 1) to Months 3, 6 and 12

Title

Change From Baseline in Forearm Circumference at Months 15, 18 and 24

Description

A negative change from Baseline represents decreased forearm circumference.

Time Frame

Baseline (Day 1) to Months 15, 18 and 24

Title

Change From Baseline in Tricep Skinfold Thickness at Months 3, 6 and 12

Description

A negative change from Baseline represents decreased Tricep Skinfold Thickness.

Time Frame

Baseline (Day 1) to Months 3, 6 and 12

Title

Change From Baseline in Tricep Skinfold Thickness at Months 15, 18 and 24

Description

A negative change from Baseline represents decreased Tricep Skinfold Thickness.

Time Frame

Baseline (Day 1) to Months 15, 18 and 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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): Documented evidence of type 2 diabetes mellitus 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) 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) Exclusion Criteria: Hepatitis B surface Antigen (HBsAg) positive Hepatitis C antibody (HCVAb) positive with the following 2 exceptions: 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 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Eric Lefebvre, MD

Organizational Affiliation

Allergan

Official's Role

Study Director

Facility Information:

City

Dothan

State/Province

Alabama

ZIP/Postal Code

36305

Country

United States

City

Phoenix

State/Province

Arizona

ZIP/Postal Code

85054

Country

United States

City

Tucson

State/Province

Arizona

ZIP/Postal Code

85712

Country

United States

City

Rialto

State/Province

California

ZIP/Postal Code

92377

Country

United States

City

San Diego

State/Province

California

ZIP/Postal Code

92120

Country

United States

City

San Diego

State/Province

California

ZIP/Postal Code

92161

Country

United States

City

San Francisco

State/Province

California

ZIP/Postal Code

94115

Country

United States

City

Littleton

State/Province

Colorado

ZIP/Postal Code

80120

Country

United States

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

City

Tampa

State/Province

Florida

ZIP/Postal Code

33606

Country

United States

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60612

Country

United States

City

Louisville

State/Province

Kentucky

ZIP/Postal Code

40202

Country

United States

City

New Orleans

State/Province

Louisiana

ZIP/Postal Code

70112

Country

United States

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21202

Country

United States

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21287

Country

United States

City

Chevy Chase

State/Province

Maryland

ZIP/Postal Code

20815

Country

United States

City

Lutherville

State/Province

Maryland

ZIP/Postal Code

21093

Country

United States

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

City

Worcester

State/Province

Massachusetts

ZIP/Postal Code

01655

Country

United States

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109

Country

United States

City

Saint Paul

State/Province

Minnesota

ZIP/Postal Code

55114

Country

United States

City

Flowood

State/Province

Mississippi

ZIP/Postal Code

39232

Country

United States

City

Jackson

State/Province

Mississippi

Country

United States

City

Tupelo

State/Province

Mississippi

ZIP/Postal Code

38801

Country

United States

City

Buffalo

State/Province

New York

ZIP/Postal Code

14201

Country

United States

City

New York

State/Province

New York

ZIP/Postal Code

10029

Country

United States

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27710

Country

United States

City

Raleigh

State/Province

North Carolina

ZIP/Postal Code

27612

Country

United States

City

Winston-Salem

State/Province

North Carolina

ZIP/Postal Code

27103

Country

United States

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45249

Country

United States

City

Chattanooga

State/Province

Tennessee

ZIP/Postal Code

37421

Country

United States

City

Germantown

State/Province

Tennessee

ZIP/Postal Code

38138

Country

United States

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

City

Houston

State/Province

Texas

ZIP/Postal Code

78234

Country

United States

City

Live Oak

State/Province

Texas

ZIP/Postal Code

78233

Country

United States

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78215

Country

United States

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78233

Country

United States

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84132

Country

United States

City

Richmond

State/Province

Virginia

ZIP/Postal Code

23298

Country

United States

City

Seattle

State/Province

Washington

ZIP/Postal Code

98104

Country

United States

City

Garran

State/Province

Australian Capital Territory

ZIP/Postal Code

2605

Country

Australia

City

Herston

State/Province

Queensland

ZIP/Postal Code

4029

Country

Australia

City

Adelaide

State/Province

South Australia

ZIP/Postal Code

5000

Country

Australia

City

Bedford Park

State/Province

South Australia

ZIP/Postal Code

5042

Country

Australia

City

Clayton

State/Province

Victoria

ZIP/Postal Code

3168

Country

Australia

City

Heidelberg

State/Province

Victoria

ZIP/Postal Code

3084

Country

Australia

City

Melbourne

State/Province

Victoria

ZIP/Postal Code

3004

Country

Australia

City

Perth

State/Province

Western Australia

ZIP/Postal Code

6000

Country

Australia

City

Brussels

ZIP/Postal Code

1070

Country

Belgium

City

Brussels

ZIP/Postal Code

1200

Country

Belgium

City

Edegem

ZIP/Postal Code

2650

Country

Belgium

City

Leuven

ZIP/Postal Code

3000

Country

Belgium

City

Angers

ZIP/Postal Code

49100

Country

France

City

Lyon cedex 04

ZIP/Postal Code

69317

Country

France

City

Montpellier Cedex 5

ZIP/Postal Code

34295

Country

France

City

Paris

ZIP/Postal Code

75012

Country

France

City

Paris

ZIP/Postal Code

75651

Country

France

City

Pessac Cedex

ZIP/Postal Code

33604

Country

France

City

Toulouse

ZIP/Postal Code

31059

Country

France

City

Vandoeuvre-les Nancy

ZIP/Postal Code

54500

Country

France

City

Villejuif

ZIP/Postal Code

94800

Country

France

City

Heidelberg

State/Province

ZIP/Postal Code

69120

Country

Germany

City

Marburg

State/Province

ZIP/Postal Code

35043

Country

Germany

City

Hamburg

State/Province

ZIP/Postal Code

20246

Country

Germany

City

Hannover

State/Province

Niedersachsen

ZIP/Postal Code

30625

Country

Germany

City

Aachen

State/Province

NRW

ZIP/Postal Code

52074

Country

Germany

City

Koeln

State/Province

NRW

ZIP/Postal Code

50937

Country

Germany

City

Leipzig

State/Province

Sachsen

ZIP/Postal Code

04103

Country

Germany

City

Leipzig

State/Province

ZIP/Postal Code

04103

Country

Germany

City

Heidelberg

State/Province

VIC

ZIP/Postal Code

3084

Country

Germany

City

Berlin

ZIP/Postal Code

13353

Country

Germany

City

Lubeck

ZIP/Postal Code

23538

Country

Germany

City

Shatin

State/Province

New Territories

Country

Hong Kong

City

Bologna

State/Province

ZIP/Postal Code

40138

Country

Italy

City

Milan

State/Province

ZIP/Postal Code

20122

Country

Italy

City

Rozzano

State/Province

ZIP/Postal Code

20089

Country

Italy

City

Palermo

State/Province

ZIP/Postal Code

90127

Country

Italy

City

Chorzow

ZIP/Postal Code

41-500

Country

Poland

City

Lodz

ZIP/Postal Code

91-347

Country

Poland

City

Myslowice

ZIP/Postal Code

41-500

Country

Poland

City

Rzeszow

ZIP/Postal Code

35-055

Country

Poland

City

Wroclaw

ZIP/Postal Code

50-349

Country

Poland

City

Alicante

ZIP/Postal Code

03010

Country

Spain

City

Barcelona

ZIP/Postal Code

08026

Country

Spain

City

Barcelona

ZIP/Postal Code

08035

Country

Spain

City

Barcelona

ZIP/Postal Code

08036

Country

Spain

City

Madrid

ZIP/Postal Code

28007

Country

Spain

City

Portsmouth

State/Province

Hampshire

ZIP/Postal Code

PO6 3LY

Country

United Kingdom

City

London

ZIP/Postal Code

E1 1BB

Country

United Kingdom

City

London

ZIP/Postal Code

NW3 2QR

Country

United Kingdom

City

Newcastle

ZIP/Postal Code

NE7 7ND

Country

United Kingdom

City

Nottingham

ZIP/Postal Code

NG7 2UH

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

34951993

Citation

Qian T, Fujiwara N, Koneru B, Ono A, Kubota N, Jajoriya AK, Tung MG, Crouchet E, Song WM, Marquez CA, Panda G, Hoshida A, Raman I, Li QZ, Lewis C, Yopp A, Rich NE, Singal AG, Nakagawa S, Goossens N, Higashi T, Koh AP, Bian CB, Hoshida H, Tabrizian P, Gunasekaran G, Florman S, Schwarz ME, Hiotis SP, Nakahara T, Aikata H, Murakami E, Beppu T, Baba H, Rew Warren, Bhatia S, Kobayashi M, Kumada H, Fobar AJ, Parikh ND, Marrero JA, Rwema SH, Nair V, Patel M, Kim-Schulze S, Corey K, O'Leary JG, Klintmalm GB, Thomas DL, Dibas M, Rodriguez G, Zhang B, Friedman SL, Baumert TF, Fuchs BC, Chayama K, Zhu S, Chung RT, Hoshida Y. Molecular Signature Predictive of Long-Term Liver Fibrosis Progression to Inform Antifibrotic Drug Development. Gastroenterology. 2022 Apr;162(4):1210-1225. doi: 10.1053/j.gastro.2021.12.250. Epub 2021 Dec 22. Erratum In: Gastroenterology. 2022 Aug;163(2):536.

Results Reference

derived

PubMed Identifier

34454994

Citation

Nielsen MJ, Leeming DJ, Goodman Z, Friedman S, Frederiksen P, Rasmussen DGK, Vig P, Seyedkazemi S, Fischer L, Torstenson R, Karsdal MA, Lefebvre E, Sanyal AJ, Ratziu V. Comparison of ADAPT, FIB-4 and APRI as non-invasive predictors of liver fibrosis and NASH within the CENTAUR screening population. J Hepatol. 2021 Dec;75(6):1292-1300. doi: 10.1016/j.jhep.2021.08.016. Epub 2021 Aug 27.

Results Reference

derived

PubMed Identifier

33666272

Citation

Parthasarathy G, Malhi H. Macrophage Heterogeneity in NASH: More Than Just Nomenclature. Hepatology. 2021 Jul;74(1):515-518. doi: 10.1002/hep.31790. Epub 2021 May 22. No abstract available.

Results Reference

derived

PubMed Identifier

31943293

Citation

Ratziu V, Sanyal A, Harrison SA, Wong VW, Francque S, Goodman Z, Aithal GP, Kowdley KV, Seyedkazemi S, Fischer L, Loomba R, Abdelmalek MF, Tacke F. Cenicriviroc Treatment for Adults With Nonalcoholic Steatohepatitis and Fibrosis: Final Analysis of the Phase 2b CENTAUR Study. Hepatology. 2020 Sep;72(3):892-905. doi: 10.1002/hep.31108. Epub 2020 Jul 21.

Results Reference

derived

PubMed Identifier

27347680

Citation

Lefebvre E, Moyle G, Reshef R, Richman LP, Thompson M, Hong F, Chou HL, Hashiguchi T, Plato C, Poulin D, Richards T, Yoneyama H, Jenkins H, Wolfgang G, Friedman SL. Antifibrotic Effects of the Dual CCR2/CCR5 Antagonist Cenicriviroc in Animal Models of Liver and Kidney Fibrosis. PLoS One. 2016 Jun 27;11(6):e0158156. doi: 10.1371/journal.pone.0158156. eCollection 2016.

Results Reference

derived

PubMed Identifier

26944023

Citation

Friedman S, Sanyal A, Goodman Z, Lefebvre E, Gottwald M, Fischer L, Ratziu V. Efficacy and safety study of cenicriviroc for the treatment of non-alcoholic steatohepatitis in adult subjects with liver fibrosis: CENTAUR Phase 2b study design. Contemp Clin Trials. 2016 Mar;47:356-65. doi: 10.1016/j.cct.2016.02.012. Epub 2016 Mar 2.

Results Reference

derived

Learn more about this trial

Efficacy and Safety Study of Cenicriviroc for the Treatment of Nonalcoholic Steatohepatitis (NASH) in Adult Participants With Liver Fibrosis

We'll reach out to this number within 24 hrs