Clincosm LogoSign in Get a demo

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

Sponsor
Tobira Therapeutics, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02217475
Collaborator
(none)
289
Enrollment
92
Locations
3
Arms
33.1
Actual Duration (Months)
3.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
289 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
CENTAUR: Efficacy and Safety Study of Cenicriviroc for the Treatment of Nonalcoholic Steatohepatitis (NASH) in Adult Subjects With Liver Fibrosis
Actual Study Start Date :
Sep 18, 2014
Actual Primary Completion Date :
Jun 30, 2016
Actual Study Completion Date :
Jun 22, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cenicriviroc (CVC) 150mg/CVC 150 mg

CVC 150 mg tablet in Years 1 and 2.

Drug: Cenicriviroc
CVC 150 mg, administered orally once daily and taken every morning with food.
Other Names:
  • TBR-652

    		•
    Experimental: Placebo/CVC 150 mg

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

    Drug: Cenicriviroc
    CVC 150 mg, administered orally once daily and taken every morning with food.
    Other Names:
  • TBR-652

    • Drug: Placebo
    Placebo administered orally once daily and taken every morning with food.
    Placebo Comparator: Placebo/Placebo

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

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

    Outcome Measures

    Primary Outcome Measures

    1. 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 [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

    1. 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 [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.

    2. 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 [Year 2]

      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.

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

    4. Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage at Year 2 [Year 2]

      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.

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

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

      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.

    7. Number of Participants With Deaths, Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading Study Drug to Discontinuation [Years 1 and 2]

      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.

    8. Number of Participants With Clinically Significant Changes in Vital Signs [Years 1 and 2]

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

    9. Number of Participants With Clinical Laboratory Abnormalities [Years 1 and 2]

      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.

    10. Number of Participants With Clinically Abnormal in Electrocardiogram (ECG) Findings [Years 1 and 2]

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

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

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

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

      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.

    14. 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 [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.

    15. 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 [Year 2]

      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.

    16. 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 [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).

    17. 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 [Year 2]

      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).

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

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

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

    21. Change From Baseline in Hepatic Tissue Fibrogenic Protein Alpha-Smooth Muscle Actin (α-SMA) at Year 2 [Baseline (Day 1) to 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.

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

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

    24. Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 1 [Baseline (Day 1) to 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.

    25. Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 2 [Baseline (Day 1) to Year 2]

      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.

    26. Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 1 [Baseline (Day 1) to 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.

    27. Change From Baseline in Portal Inflammation Grade on Liver Biopsy at Year 2 [Baseline (Day 1) to 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.

    28. Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 3, 6 and 12 [Baseline (Month 0) to 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.

    29. Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Aspartate Aminotransferase to Platelet Count Ratio Index (APRI) at Months 15, 18 and 24 [Baseline (Month 0) to Months 15, 18 and 24]

      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.

    30. Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 3, 6 and 12 [Baseline (Month 0) to 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.

    31. Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 15, 18 and 24 [Baseline (Month 0) to Months 15, 18 and 24]

      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.

    32. Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 6 and 12 [Baseline (Month 0) to Months 6 and 12]

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

    33. Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Hyaluronic Acid at Months 18 and 24 [Baseline (Month 0) to Months 18 and 24]

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

    34. Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Nonalcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) at Months 3, 6 and 12 [Baseline (Month 0) to 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.

    35. Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: NAFLD Fibrosis Score (NFS) at Months 15, 18 and 24 [Baseline (Month 0) to Months 15, 18 and 24]

      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.

    36. Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 6 and 12 [Baseline (Month 0) to 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.

    37. Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 18 and 24 [Baseline (Month 0) to Months 18 and 24]

      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.

    38. 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 [Baseline (Month 0) to 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.

    39. 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 [Baseline (Month 0) to Months 15, 18 and 24]

      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.

    40. Change From Baseline in Weight at Months 3, 6 and 12 [Baseline (Day 1) to Months 3, 6 and 12]

      A negative change from Baseline represents decreased weight.

    41. Change From Baseline in Weight at Months 15, 18 and 24 [Baseline (Day 1) to Months 15, 18 and 24]

      A negative change from Baseline represents decreased weight.

    42. Change From Baseline in Body Mass Index (BMI) at Months 3, 6 and 12 [Baseline (Day 1) to 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.

    43. Change From Baseline in Body Mass Index (BMI) at Months 15, 18 and 24 [Baseline (Day 1) to Months 15, 18 and 24]

      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.

    44. Change From Baseline in Waist Circumference at Months 3, 6 and 12 [Baseline (Day 1) to Months 3, 6 and 12]

      A negative change from Baseline represents decreased in waist circumference.

    45. Change From Baseline in Waist Circumference at Months 15, 18 and 24 [Baseline (Day 1) to Months 15, 18 and 24]

      A negative change from Baseline represents decreased in waist circumference.

    46. Change From Baseline in Hip Circumference at Months 3, 6 and 12 [Baseline (Day 1) to Months 3, 6 and 12]

      A negative change from Baseline represents decreased hip circumference.

    47. Change From Baseline in Hip Circumference at Months 15, 18 and 24 [Baseline (Day 1) to Months 15, 18 and 24]

      A negative change from Baseline represents decreased hip circumference.

    48. Change From Baseline in Forearm Circumference at Months 3, 6 and 12 [Baseline (Day 1) to Months 3, 6 and 12]

      A negative change from Baseline represents decreased forearm circumference.

    49. Change From Baseline in Forearm Circumference at Months 15, 18 and 24 [Baseline (Day 1) to Months 15, 18 and 24]

      A negative change from Baseline represents decreased forearm circumference.

    50. Change From Baseline in Tricep Skinfold Thickness at Months 3, 6 and 12 [Baseline (Day 1) to Months 3, 6 and 12]

      A negative change from Baseline represents decreased Tricep Skinfold Thickness.

    51. Change From Baseline in Tricep Skinfold Thickness at Months 15, 18 and 24 [Baseline (Day 1) to Months 15, 18 and 24]

      A negative change from Baseline represents decreased Tricep Skinfold Thickness.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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)

    1. 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Dothan Alabama United States 36305
    2 Phoenix Arizona United States 85054
    3 Tucson Arizona United States 85712
    4 Rialto California United States 92377
    5 San Diego California United States 92120
    6 San Diego California United States 92161
    7 San Francisco California United States 94115
    8 Littleton Colorado United States 80120
    9 Miami Florida United States 33136
    10 Tampa Florida United States 33606
    11 Chicago Illinois United States 60612
    12 Louisville Kentucky United States 40202
    13 New Orleans Louisiana United States 70112
    14 Baltimore Maryland United States 21202
    15 Baltimore Maryland United States 21287
    16 Chevy Chase Maryland United States 20815
    17 Lutherville Maryland United States 21093
    18 Boston Massachusetts United States 02114
    19 Worcester Massachusetts United States 01655
    20 Ann Arbor Michigan United States 48109
    21 Saint Paul Minnesota United States 55114
    22 Flowood Mississippi United States 39232
    23 Jackson Mississippi United States
    24 Tupelo Mississippi United States 38801
    25 Buffalo New York United States 14201
    26 New York New York United States 10029
    27 Durham North Carolina United States 27710
    28 Raleigh North Carolina United States 27612
    29 Winston-Salem North Carolina United States 27103
    30 Cincinnati Ohio United States 45249
    31 Chattanooga Tennessee United States 37421
    32 Germantown Tennessee United States 38138
    33 Houston Texas United States 77030
    34 Houston Texas United States 78234
    35 Live Oak Texas United States 78233
    36 San Antonio Texas United States 78215
    37 San Antonio Texas United States 78233
    38 Salt Lake City Utah United States 84132
    39 Richmond Virginia United States 23298
    40 Seattle Washington United States 98104
    41 Garran Australian Capital Territory Australia 2605
    42 Herston Queensland Australia 4029
    43 Adelaide South Australia Australia 5000
    44 Bedford Park South Australia Australia 5042
    45 Clayton Victoria Australia 3168
    46 Heidelberg Victoria Australia 3084
    47 Melbourne Victoria Australia 3004
    48 Perth Western Australia Australia 6000
    49 Brussels Belgium 1070
    50 Brussels Belgium 1200
    51 Edegem Belgium 2650
    52 Leuven Belgium 3000
    53 Angers France 49100
    54 Lyon cedex 04 France 69317
    55 Montpellier Cedex 5 France 34295
    56 Paris France 75012
    57 Paris France 75651
    58 Pessac Cedex France 33604
    59 Toulouse France 31059
    60 Vandoeuvre-les Nancy France 54500
    61 Villejuif France 94800
    62 Heidelberg BW Germany 69120
    63 Marburg HE Germany 35043
    64 Hamburg HH Germany 20246
    65 Hannover Niedersachsen Germany 30625
    66 Aachen NRW Germany 52074
    67 Koeln NRW Germany 50937
    68 Leipzig Sachsen Germany 04103
    69 Leipzig SN Germany 04103
    70 Heidelberg VIC Germany 3084
    71 Berlin Germany 13353
    72 Lubeck Germany 23538
    73 Shatin New Territories Hong Kong
    74 Bologna BO Italy 40138
    75 Milan MI Italy 20122
    76 Rozzano MI Italy 20089
    77 Palermo PA Italy 90127
    78 Chorzow Poland 41-500
    79 Lodz Poland 91-347
    80 Myslowice Poland 41-500
    81 Rzeszow Poland 35-055
    82 Wroclaw Poland 50-349
    83 Alicante Spain 03010
    84 Barcelona Spain 08026
    85 Barcelona Spain 08035
    86 Barcelona Spain 08036
    87 Madrid Spain 28007
    88 Portsmouth Hampshire United Kingdom PO6 3LY
    89 London United Kingdom E1 1BB
    90 London United Kingdom NW3 2QR
    91 Newcastle United Kingdom NE7 7ND
    92 Nottingham United Kingdom NG7 2UH

    Sponsors and Collaborators

    • Tobira Therapeutics, Inc.

    Investigators

    • Study Director: Eric Lefebvre, MD, Allergan

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Tobira Therapeutics, Inc.
    ClinicalTrials.gov Identifier:
    NCT02217475
    Other Study ID Numbers:
    • 652-2-203
    • 2016-004754-15
    First Posted:
    Aug 15, 2014
    Last Update Posted:
    May 10, 2019
    Last Verified:
    Mar 1, 2019
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Fatty Liver
    Non-alcoholic Fatty Liver Disease
    Liver Cirrhosis
    Cenicriviroc

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail In total, 812 participants were screened, and 289 participants were randomized to treatment period 1. Of the 289 participants randomized, 250 participants completed Treatment Period 1. A total of 242 participants entered Treatment Period 2 and 212 completed.
    Arm/Group Title Placebo/Placebo Placebo/Cenicriviroc (CVC) 150 mg CVC 150mg/CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2. Placebo-matching CVC tablet, once daily in the morning with food in Year 1 then CVC 150 mg tablet, once daily in the morning with food in Year 2. CVC 150 mg tablet, once daily in the morning with food in Years 1 and 2.
    Period Title: Treatment Period 1 (Year 1)
    STARTED 72 72 145
    Safety Analysis Set 72 72 144
    COMPLETED 62 64 124
    NOT COMPLETED 10 8 21
    Period Title: Treatment Period 1 (Year 1)
    STARTED 62 64 124
    COMPLETED 60 61 121
    NOT COMPLETED 2 3 3
    Period Title: Treatment Period 1 (Year 1)
    STARTED 60 61 121
    COMPLETED 58 59 109
    NOT COMPLETED 2 2 12

    Baseline Characteristics

    Arm/Group Title CVC 150mg/CVC 150 mg Placebo/Cenicriviroc (CVC) 150 mg Placebo/Placebo Total
    Arm/Group Description CVC 150 mg tablet, once daily in the morning with food in Years 1 and 2. Placebo-matching CVC tablet, once daily in the morning with food in Year 1 then CVC 150 mg tablet, once daily in the morning with food in Year 2. Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2. Total of all reporting groups
    Overall Participants 145 72 72 289
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    54.6
    (10.22)
    55.3
    (10.38)
    52.1
    (11.37)
    54.1
    (10.59)
    Sex: Female, Male (Count of Participants)
    Female
    73
    50.3%
    39
    54.2%
    40
    55.6%
    152
    52.6%
    Male
    72
    49.7%
    33
    45.8%
    32
    44.4%
    137
    47.4%
    Race/Ethnicity, Customized (Count of Participants)
    Hispanic or Latino
    23
    15.9%
    18
    25%
    7
    9.7%
    48
    16.6%
    Not Hispanic or Latino
    122
    84.1%
    51
    70.8%
    65
    90.3%
    238
    82.4%
    Not reported
    0
    0%
    2
    2.8%
    0
    0%
    2
    0.7%
    Unknown
    0
    0%
    1
    1.4%
    0
    0%
    1
    0.3%
    Race/Ethnicity, Customized (Count of Participants)
    Asian
    6
    4.1%
    6
    8.3%
    9
    12.5%
    21
    7.3%
    American Indian or Alaska Native
    0
    0%
    0
    0%
    1
    1.4%
    1
    0.3%
    Black or African American
    5
    3.4%
    1
    1.4%
    2
    2.8%
    8
    2.8%
    Native Hawaiian or Other Pacific Islander
    3
    2.1%
    0
    0%
    0
    0%
    3
    1%
    White
    129
    89%
    63
    87.5%
    58
    80.6%
    250
    86.5%
    Other
    2
    1.4%
    2
    2.8%
    2
    2.8%
    6
    2.1%

    Outcome Measures

    1. Primary Outcome
    Title 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
    Description 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.
    Time Frame Year 1

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population included all randomized participants regardless of starting treatment.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1. Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.
    Measure Participants 144 145
    Count of Participants [Participants]
    27
    18.6%
    23
    31.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, CVC 150 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5194
    Comments
    Method Regression, Logistic
    Comments Logistic regression model was used for analysis. Randomized treatment group, NAS score at screening and fibrosis stage were the factors.
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.816
    Confidence Interval (2-Sided) 95%
    0.439 to 1.516
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title 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
    Description 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.
    Time Frame Year 1

    Outcome Measure Data

    Analysis Population Description
    ITT population included all randomized participants regardless of starting treatment.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1. Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.
    Measure Participants 144 145
    Count of Participants [Participants]
    4
    2.8%
    7
    9.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, CVC 150 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0388
    Comments
    Method Regression, Logistic
    Comments Logistic regression model was used for analysis. Randomized treatment group, NAS score at screening and fibrosis stage were the factors.
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.934
    Confidence Interval (2-Sided) 95%
    1.035 to 3.614
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title 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
    Description 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.
    Time Frame Year 2

    Outcome Measure Data

    Analysis Population Description
    ITT population Year 2 included all participants who had an evaluable year 1 biopsy and received at least 1 dose of study drug during Year 2.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Cenicriviroc 150 mg tablet or placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2.
    Measure Participants 57 178
    Count of Participants [Participants]
    2
    1.4%
    5
    6.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, CVC 150 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5920
    Comments
    Method Regression, Logistic
    Comments Logistic regression model was used for analysis. Randomized treatment group, NAS score at screening and fibrosis stage were the factors.
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.249
    Confidence Interval (2-Sided) 95%
    0.553 to 2.821
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage at Year 1
    Description 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.
    Time Frame Year 1

    Outcome Measure Data

    Analysis Population Description
    ITT population included all randomized participants regardless of starting treatment.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1. Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.
    Measure Participants 144 145
    Count of Participants [Participants]
    8
    5.5%
    11
    15.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, CVC 150 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4941
    Comments
    Method Regression, Logistic
    Comments Logistic regression model was used for analysis. Randomized treatment group, NAS score at screening and fibrosis stage were the factors.
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.396
    Confidence Interval (2-Sided) 95%
    0.537 to 3.628
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage at Year 2
    Description 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.
    Time Frame Year 2

    Outcome Measure Data

    Analysis Population Description
    ITT population Year 2 included all participants who had an evaluable year 1 biopsy and received at least 1 dose of study drug during Year 2.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Cenicriviroc 150 mg tablet or placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2.
    Measure Participants 57 178
    Count of Participants [Participants]
    3
    2.1%
    11
    15.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, CVC 150 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.8434
    Comments
    Method Regression, Logistic
    Comments Logistic regression model was used for analysis. Randomized treatment group, NAS score at screening and fibrosis stage were the factors.
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.142
    Confidence Interval (2-Sided) 95%
    0.305 to 4.277
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    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 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.
    Time Frame Year 1

    Outcome Measure Data

    Analysis Population Description
    ITT population included all randomized participants regardless of starting treatment.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1. Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.
    Measure Participants 144 145
    Count of Participants [Participants]
    15
    10.3%
    29
    40.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, CVC 150 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0234
    Comments
    Method Regression, Logistic
    Comments Logistic regression model was used for analysis. Randomized treatment group, NAS score at screening and fibrosis stage were the factors.
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.201
    Confidence Interval (2-Sided) 95%
    1.113 to 4.352
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    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 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.
    Time Frame Year 2

    Outcome Measure Data

    Analysis Population Description
    ITT analysis set Year 2 included all participants who have an evaluable year 1 biopsy and who received at least one dose of study drug during Year 2 (after the 1 year biopsy).
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Cenicriviroc 150 mg tablet or placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2.
    Measure Participants 57 178
    Count of Participants [Participants]
    8
    5.5%
    27
    37.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, CVC 150 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.7474
    Comments
    Method Regression, Logistic
    Comments Logistic regression model was used for analysis. Randomized treatment group, NAS score at screening and fibrosis stage were the factors.
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.154
    Confidence Interval (2-Sided) 95%
    0.484 to 2.752
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title Number of Participants With Deaths, Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading Study Drug to Discontinuation
    Description 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.
    Time Frame Years 1 and 2

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
    Arm/Group Title CVC 150 mg/CVC 150 mg Placebo/CVC 150 mg Placebo/Placebo
    Arm/Group Description CVC 150 mg tablet, once daily in the morning with food in Years 1 and 2. Placebo-matching CVC tablet, once daily in the morning with food in Year 1 then CVC 150 mg tablet, once daily in the morning with food in Year 2. Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.
    Measure Participants 144 72 72
    Deaths
    0
    0%
    0
    0%
    0
    0%
    TEAEs
    137
    94.5%
    68
    94.4%
    70
    97.2%
    SAEs
    25
    17.2%
    8
    11.1%
    12
    16.7%
    TEAEs Leading Study Drug to Discontinuation
    14
    9.7%
    8
    11.1%
    5
    6.9%
    9. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
    Arm/Group Title CVC 150 mg/CVC 150 mg Placebo/CVC 150 mg Placebo/Placebo
    Arm/Group Description CVC 150 mg tablet, once daily in the morning with food in Years 1 and 2. Placebo-matching CVC tablet, once daily in the morning with food in Year 1 then CVC 150 mg tablet, once daily in the morning with food in Year 2. Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.
    Measure Participants 144 72 72
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    10. Secondary Outcome
    Title Number of Participants With Clinical Laboratory Abnormalities
    Description 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.
    Time Frame Years 1 and 2

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
    Arm/Group Title CVC 150 mg (Year 1) Placebo (Year 1) CVC 150 mg Placebo Then CVC 150 mg Placebo Then Placebo
    Arm/Group Description CVC 150 mg tablet, once daily in the morning with food in Year 1. Placebo-matching cenicriviroc tablet once daily in the morning with food in Year 1. Cenicriviroc 150 mg tablet or placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2. Includes AEs that occurred in Year 2. Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Includes AEs that occurred in Year 2.
    Measure Participants 144 144 121 61 60
    Fasting glucose (Grade 3)
    17
    11.7%
    13
    18.1%
    10
    13.9%
    6
    2.1%
    5
    NaN
    Fasting glucose (Grade 4)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    NaN
    ALT (Grade 3)
    17
    11.7%
    17
    23.6%
    4
    5.6%
    3
    1%
    2
    NaN
    ALT (Grade 4)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    NaN
    AST (Grade 3)
    7
    4.8%
    10
    13.9%
    1
    1.4%
    3
    1%
    1
    NaN
    AST (Grade 4)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    NaN
    APT/PTT (Grade 3)
    4
    2.8%
    2
    2.8%
    1
    1.4%
    1
    0.3%
    2
    NaN
    Triglycerides (Grade 3)
    5
    3.4%
    7
    9.7%
    6
    8.3%
    5
    1.7%
    2
    NaN
    Triglycerides (Grade 4)
    3
    2.1%
    3
    4.2%
    2
    2.8%
    0
    0%
    1
    NaN
    GGT (Grade 3)
    8
    5.5%
    7
    9.7%
    8
    11.1%
    2
    0.7%
    2
    NaN
    GGT (Grade 4)
    1
    0.7%
    1
    1.4%
    1
    1.4%
    0
    0%
    0
    NaN
    Creatine kinase (Grade 3)
    6
    4.1%
    7
    9.7%
    1
    1.4%
    2
    0.7%
    4
    NaN
    Creatine kinase (Grade 4)
    2
    1.4%
    2
    2.8%
    3
    4.2%
    1
    0.3%
    0
    NaN
    Uric acid (Grade 3)
    9
    6.2%
    8
    11.1%
    4
    5.6%
    3
    1%
    2
    NaN
    Uric acid (Grade 4)
    11
    7.6%
    6
    8.3%
    5
    6.9%
    1
    0.3%
    6
    NaN
    Amylase (Grade 3)
    6
    4.1%
    1
    1.4%
    4
    5.6%
    0
    0%
    1
    NaN
    Amylase (Grade 4)
    3
    2.1%
    0
    0%
    2
    2.8%
    0
    0%
    0
    NaN
    Lipase (Grade 3)
    4
    2.8%
    2
    2.8%
    3
    4.2%
    0
    0%
    1
    NaN
    Lipase (Grade 4)
    5
    3.4%
    0
    0%
    3
    4.2%
    0
    0%
    1
    NaN
    Phosphorus (Grade 3)
    5
    3.4%
    2
    2.8%
    2
    2.8%
    1
    0.3%
    1
    NaN
    Phosphorus (Grade 4)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    NaN
    Absolute neutrophil (Grade 3)
    2
    1.4%
    3
    4.2%
    3
    4.2%
    0
    0%
    1
    NaN
    Absolute neutrophil (Grade 4)
    2
    1.4%
    1
    1.4%
    1
    1.4%
    1
    0.3%
    1
    NaN
    11. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
    Arm/Group Title CVC 150 mg/CVC 150 mg Placebo/CVC 150 mg Placebo/Placebo
    Arm/Group Description CVC 150 mg tablet, once daily in the morning with food in Years 1 and 2. Placebo-matching CVC tablet, once daily in the morning with food in Year 1 then CVC 150 mg tablet, once daily in the morning with food in Year 2. Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.
    Measure Participants 144 72 72
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    12. Secondary Outcome
    Title Number of Participants With Hepatic Histological Improvement in NAS at Year 2
    Description 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.
    Time Frame Year 2

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS) in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Cenicriviroc 150 mg tablet or placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2.
    Measure Participants 72 215
    Count of Participants [Participants]
    7
    4.8%
    24
    33.3%
    13. Secondary Outcome
    Title Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 1
    Description 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.
    Time Frame Year 1

    Outcome Measure Data

    Analysis Population Description
    FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1. Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.
    Measure Participants 126 126
    Baseline (Steatosis)
    1.4
    (0.55)
    1.3
    (0.57)
    Change from Baseline (Steatosis)
    -0.1
    (0.66)
    -0.2
    (0.56)
    Baseline (Lobular Inflammation)
    2.5
    (0.56)
    2.4
    (0.58)
    Change from Baseline (Lobular Inflammation)
    -0.1
    (0.79)
    -0.1
    (0.88)
    Baseline (Hepatocellular Ballooning)
    1.5
    (0.50)
    1.5
    (0.50)
    Change from Baseline (Hepatocellular Ballooning)
    -0.2
    (0.75)
    -0.1
    (0.75)
    14. Secondary Outcome
    Title Change From Baseline in the 3 Categorical Features of NAS (Steatosis, Lobular Inflammation, Hepatocellular Ballooning) at Year 2
    Description 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.
    Time Frame Year 2

    Outcome Measure Data

    Analysis Population Description
    FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Cenicriviroc 150 mg tablet or placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2.
    Measure Participants 54 159
    Baseline (Steatosis)
    1.5
    (0.54)
    1.3
    (0.52)
    Change from Baseline (Steatosis)
    -0.4
    (0.56)
    -0.2
    (0.50)
    Baseline (Lobular Inflammation)
    2.4
    (0.63)
    2.4
    (0.54)
    Change from Baseline (Lobular Inflammation)
    0.1
    (0.72)
    0.0
    (0.84)
    Baseline (Hepatocellular Ballooning)
    1.5
    (0.50)
    1.5
    (0.50)
    Change from Baseline (Hepatocellular Ballooning)
    -0.1
    (0.68)
    0.0
    (0.83)
    15. Secondary Outcome
    Title 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
    Description 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.
    Time Frame Year 1

    Outcome Measure Data

    Analysis Population Description
    FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1. Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.
    Measure Participants 143 144
    Count of Participants [Participants]
    24
    16.6%
    22
    30.6%
    16. Secondary Outcome
    Title 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
    Description 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.
    Time Frame Year 2

    Outcome Measure Data

    Analysis Population Description
    FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Cenicriviroc 150 mg tablet or placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2.
    Measure Participants 72 215
    Count of Participants [Participants]
    6
    4.1%
    20
    27.8%
    17. Secondary Outcome
    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 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).
    Time Frame Year 1

    Outcome Measure Data

    Analysis Population Description
    FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1. Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.
    Measure Participants 143 144
    Count of Participants [Participants]
    7
    4.8%
    6
    8.3%
    18. Secondary Outcome
    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 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).
    Time Frame Year 2

    Outcome Measure Data

    Analysis Population Description
    FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Cenicriviroc 150 mg tablet or placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2.
    Measure Participants 72 215
    Count of Participants [Participants]
    1
    0.7%
    9
    12.5%
    19. Secondary Outcome
    Title Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 1
    Description 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.
    Time Frame Year 1

    Outcome Measure Data

    Analysis Population Description
    FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1. Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.
    Measure Participants 123 121
    Baseline
    2.49
    (2.004)
    2.37
    (1.827)
    Change from Baseline to Year 1
    -0.14
    (2.389)
    0.02
    (2.357)
    20. Secondary Outcome
    Title Change From Baseline in Morphometric Quantitative Collagen on Liver Biopsy at Year 2
    Description 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.
    Time Frame Year 2

    Outcome Measure Data

    Analysis Population Description
    FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Cenicriviroc 150 mg tablet or placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2.
    Measure Participants 51 150
    Baseline
    2.57
    (2.156)
    2.48
    (1.892)
    Change from Baseline to Year 2
    -0.17
    (2.576)
    -0.09
    (2.160)
    21. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1. Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.
    Measure Participants 122 122
    Baseline
    2.41
    (2.264)
    2.49
    (2.885)
    Change from Baseline to Year 1
    0.77
    (3.529)
    0.79
    (3.861)
    22. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Cenicriviroc 150 mg tablet or placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2.
    Measure Participants 52 152
    Baseline
    2.47
    (2.679)
    2.44
    (2.505)
    Change from Baseline to Year 2
    2.10
    (4.533)
    1.38
    (3.793)
    23. Secondary Outcome
    Title Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 1
    Description 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.
    Time Frame Year 1

    Outcome Measure Data

    Analysis Population Description
    FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1. Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.
    Measure Participants 123 121
    Baseline
    22.42
    (10.016)
    21.58
    (8.740)
    Change from Baseline to Year 1
    -3.39
    (9.120)
    -2.79
    (8.127)
    24. Secondary Outcome
    Title Change From Baseline in Morphometric Quantitative Fat Content on Liver Biopsy at Year 2
    Description 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.
    Time Frame Year 2

    Outcome Measure Data

    Analysis Population Description
    FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Cenicriviroc 150 mg tablet or placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2.
    Measure Participants 50 150
    Baseline
    23.30
    (10.300)
    21.62
    (9.575)
    Change from Baseline to Year 2
    -5.06
    (9.739)
    -2.96
    (9.230)
    25. Secondary Outcome
    Title Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 1
    Description 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.
    Time Frame Baseline (Day 1) to Year 1

    Outcome Measure Data

    Analysis Population Description
    FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1. Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.
    Measure Participants 126 126
    Baseline (NASH CRN Fibrosis Stage)
    2.1
    (0.86)
    2.0
    (0.85)
    Change from Baseline (NASH CRN Fibrosis Stage)
    0.2
    (0.92)
    0.0
    (1.00)
    Baseline (Ishak Fibrosis Stage)
    2.2
    (1.00)
    2.2
    (1.05)
    Change from Baseline (Ishak Fibrosis Stage)
    0.2
    (1.10)
    0.0
    (1.20)
    26. Secondary Outcome
    Title Change From Baseline in Histologic Fibrosis Stage (NASH CRN System and Ishak Scale Score) at Year 2
    Description 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.
    Time Frame Baseline (Day 1) to Year 2

    Outcome Measure Data

    Analysis Population Description
    FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Cenicriviroc 150 mg tablet or placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2.
    Measure Participants 54 159
    Baseline (NASH CRN Fibrosis Stage)
    2.0
    (0.88)
    2.1
    (0.85)
    Change from Baseline (NASH CRN Fibrosis Stage)
    0.0
    (0.89)
    0.0
    (1.08)
    Baseline (Ishak Fibrosis Stage)
    2.1
    (1.00)
    2.2
    (1.04)
    Change from Baseline (Ishak Fibrosis Stage)
    0.1
    (1.21)
    0.0
    (1.26)
    27. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1. Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.
    Measure Participants 126 124
    Baseline
    1.6
    (0.63)
    1.5
    (0.64)
    Change from Baseline to Year 1
    0.0
    (0.76)
    0.2
    (0.74)
    28. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Cenicriviroc 150 mg tablet or placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2.
    Measure Participants 54 159
    Baseline
    1.5
    (0.64)
    1.6
    (0.67)
    Change from Baseline to Year 1
    0.1
    (0.75)
    0.2
    (0.72)
    29. Secondary Outcome
    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 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.
    Time Frame Baseline (Month 0) to Months 3, 6 and 12

    Outcome Measure Data

    Analysis Population Description
    FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1. Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.
    Measure Participants 143 144
    Baseline (Month 3)
    0.649
    (0.3661)
    0.596
    (0.4089)
    Change from Baseline to Month 3
    -0.005
    (0.3012)
    0.065
    (0.3152)
    Baseline (Month 6)
    0.663
    (0.3811)
    0.578
    (0.3794)
    Change from Baseline to Month 6
    0.009
    (0.3968)
    0.102
    (0.4536)
    Baseline (Month 12)
    0.662
    (0.3915)
    0.580
    (0.3939)
    Change from Baseline to Month 12
    0.066
    (0.5572)
    0.093
    (0.3852)
    30. Secondary Outcome
    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 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.
    Time Frame Baseline (Month 0) to Months 15, 18 and 24

    Outcome Measure Data

    Analysis Population Description
    FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Cenicriviroc 150 mg tablet or placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2.
    Measure Participants 72 215
    Baseline (Month 15)
    0.619
    (0.3157)
    0.584
    (0.3572)
    Change from Baseline to Month 15
    0.002
    (0.3422)
    0.118
    (0.4095)
    Baseline (Month 18)
    0.620
    (0.3305)
    0.586
    (0.3612)
    Change from Baseline to Month 18
    0.038
    (0.4033)
    0.133
    (0.4269)
    Baseline (Month 24)
    0.633
    (0.3156)
    0.584
    (0.3617)
    Change from Baseline to Month 24
    -0.020
    (0.4721)
    0.086
    (0.4153)
    31. Secondary Outcome
    Title Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 3, 6 and 12
    Description 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.
    Time Frame Baseline (Month 0) to Months 3, 6 and 12

    Outcome Measure Data

    Analysis Population Description
    FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1. Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.
    Measure Participants 143 144
    Baseline (Month 3)
    1.444
    (0.6753)
    1.417
    (0.6893)
    Change from Baseline to Month 3
    0.021
    (0.4236)
    0.071
    (0.4209)
    Baseline (Month 6)
    1.500
    (0.7268)
    1.388
    (0.6771)
    Change from Baseline to Month 6
    0.015
    (0.4591)
    0.099
    (0.5246)
    Baseline (Month 12)
    1.503
    (0.7442)
    1.398
    (0.6834)
    Change from Baseline to Month 12
    0.106
    (0.6876)
    0.117
    (0.5069)
    32. Secondary Outcome
    Title Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at Months 15, 18 and 24
    Description 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.
    Time Frame Baseline (Month 0) to Months 15, 18 and 24

    Outcome Measure Data

    Analysis Population Description
    FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Cenicriviroc 150 mg tablet or placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2.
    Measure Participants 72 215
    Baseline (Month 15)
    1.409
    (0.6706)
    1.440
    (0.6714)
    Change from Baseline to Month 15
    0.075
    (0.5982)
    0.213
    (0.6462)
    Baseline (Month 18)
    1.389
    (0.6699)
    1.440
    (0.6895)
    Change from Baseline to Month 18
    0.094
    (0.5891)
    0.219
    (0.5559)
    Baseline (Month 24)
    1.426
    (0.6841)
    1.444
    (0.6838)
    Change from Baseline to Month 24
    0.064
    (0.8103)
    0.166
    (0.6086)
    33. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1. Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.
    Measure Participants 143 144
    Baseline (Month 6)
    68.7
    (107.63)
    68.2
    (78.88)
    Change from Baseline to Month 6
    -2.4
    (75.03)
    10.7
    (79.58)
    Baseline (Month 12)
    70.7
    (110.49)
    69.5
    (80.56)
    Change from Baseline to Month 12
    -0.2
    (81.30)
    10.9
    (58.46)
    34. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Cenicriviroc 150 mg tablet or placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2.
    Measure Participants 72 215
    Baseline (Month 18)
    46.4
    (32.67)
    79.6
    (111.36)
    Change from Baseline to Month 18
    5.7
    (34.66)
    1.4
    (81.20)
    Baseline (Month 24)
    46.6
    (32.91)
    79.7
    (112.46)
    Change from Baseline to Month 24
    19.3
    (70.64)
    13.0
    (95.00)
    35. Secondary Outcome
    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 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.
    Time Frame Baseline (Month 0) to Months 3, 6 and 12

    Outcome Measure Data

    Analysis Population Description
    FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1. Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.
    Measure Participants 143 144
    Baseline (Month 3)
    -1.227
    (1.5255)
    -1.012
    (1.2558)
    Change from Baseline to Month 3
    0.029
    (0.5150)
    0.087
    (0.4608)
    Baseline (Month 6)
    -1.119
    (1.4935)
    -1.064
    (1.2403)
    Change from Baseline to Month 6
    0.051
    (0.4747)
    0.094
    (0.5460)
    Baseline (Month 12)
    -1.132
    (1.4609)
    -1.040
    (1.1393)
    Change from Baseline to Month 12
    0.121
    (0.5117)
    0.139
    (0.5016)
    36. Secondary Outcome
    Title Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: NAFLD Fibrosis Score (NFS) at Months 15, 18 and 24
    Description 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.
    Time Frame Baseline (Month 0) to Months 15, 18 and 24

    Outcome Measure Data

    Analysis Population Description
    FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Cenicriviroc 150 mg tablet or placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2.
    Measure Participants 72 215
    Baseline (Month 15)
    -1.252
    (1.4602)
    -1.051
    (1.3410)
    Change from Baseline to Month 15
    0.057
    (0.5981)
    0.225
    (0.5654)
    Baseline (Month 18)
    -1.284
    (1.4910)
    -1.057
    (1.3309)
    Change from Baseline to Month 18
    0.046
    (0.5809)
    0.196
    (0.5583)
    Baseline (Month 24)
    -1.245
    (1.4778)
    -1.100
    (1.3228)
    Change from Baseline to Month 24
    0.046
    (0.6188)
    0.185
    (0.6184)
    37. Secondary Outcome
    Title Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 6 and 12
    Description 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.
    Time Frame Baseline (Month 0) to Months 6 and 12

    Outcome Measure Data

    Analysis Population Description
    FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1. Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.
    Measure Participants 143 144
    Baseline (Month 6)
    -0.786
    (0.7179)
    -0.837
    (0.7238)
    Change from Baseline to Month 6
    -0.022
    (0.4901)
    0.060
    (0.5228)
    Baseline (Month 12)
    -0.795
    (0.7435)
    -0.801
    (0.7162)
    Change from Baseline to Month 12
    -0.064
    (0.5602)
    0.041
    (0.5727)
    38. Secondary Outcome
    Title Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Months 18 and 24
    Description 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.
    Time Frame Baseline (Month 0) to Months 18 and 24

    Outcome Measure Data

    Analysis Population Description
    FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Cenicriviroc 150 mg tablet or placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2.
    Measure Participants 72 215
    Baseline (Month 18)
    -0.931
    (0.6387)
    -0.758
    (0.7307)
    Change from Baseline to Month 18
    -0.129
    (0.6606)
    -0.087
    (0.6113)
    Baseline (Month 24)
    -0.940
    (0.6587)
    -0.765
    (0.7127)
    Change from Baseline to Month 24
    -0.024
    (0.7375)
    0.096
    (0.6437)
    39. Secondary Outcome
    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 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.
    Time Frame Baseline (Month 0) to Months 3, 6 and 12

    Outcome Measure Data

    Analysis Population Description
    FAS in Year 1 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1. Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.
    Measure Participants 143 144
    Baseline (Month 3)
    601.6
    (431.77)
    594.2
    (554.20)
    Change from Baseline to Month 3
    -56.4
    (451.14)
    -59.0
    (485.76)
    Baseline (Month 6)
    550.3
    (360.64)
    552.9
    (393.92)
    Change from Baseline to Month 6
    10.6
    (461.98)
    -26.1
    (512.88)
    Baseline (Month 12)
    555.3
    (356.28)
    567.9
    (500.53)
    Change from Baseline to Month 12
    99.7
    (824.50)
    107.8
    (830.28)
    40. Secondary Outcome
    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 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.
    Time Frame Baseline (Month 0) to Months 15, 18 and 24

    Outcome Measure Data

    Analysis Population Description
    FAS in Year 2 included all participants who were randomized and received at least 1 dose of study drug, had a measurable Screening biopsy, and had no major eligibility violations. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Cenicriviroc 150 mg tablet or placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2.
    Measure Participants 72 215
    CK-18(M30), Baseline (Month 15)
    570.8
    (297.42)
    536.4
    (459.06)
    CK-18(M30), Change from Baseline to Month 15
    -39.6
    (287.44)
    -13.3
    (450.16)
    CK-18(M30), Baseline (Month 18)
    578.8
    (293.93)
    540.9
    (453.90)
    CK-18(M30), Change from Baseline to Month 18
    23.8
    (402.98)
    57.3
    (476.92)
    CK-18(M30), Baseline (Month 24)
    575.4
    (293.64)
    541.8
    (462.29)
    CK-18(M30), Change from Baseline to Month 24
    -30.0
    (369.60)
    39.7
    (437.60)
    CK-18(M65), Baseline (Month 15)
    772.7
    (337.24)
    687.4
    (404.83)
    CK-18(M65), Change from Baseline to Month 15
    134.7
    (534.46)
    88.6
    (559.11)
    CK-18(M65), Baseline (Month 18)
    777.8
    (344.07)
    694.8
    (401.88)
    CK-18(M65), Change from Baseline to Month 18
    158.0
    (732.63)
    181.5
    (620.57)
    CK-18(M65), Baseline (Month 24)
    770.2
    (335.05)
    693.9
    (409.88)
    CK-18(M65), Change from Baseline to Month 24
    7.4
    (570.92)
    124.9
    (522.08)
    41. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set Year 1 included all participants who received at least 1 dose of study drug. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1. Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.
    Measure Participants 144 144
    Baseline (Month 3)
    97.21
    (22.368)
    95.59
    (20.590)
    Change from Baseline to Month 3
    -0.50
    (2.652)
    -0.63
    (2.632)
    Baseline (Month 6)
    97.18
    (22.224)
    95.18
    (20.386)
    Change from Baseline to Month 6
    -0.55
    (3.319)
    -0.47
    (3.466)
    Baseline (Month 12)
    96.63
    (22.139)
    95.06
    (20.651)
    Change from Baseline to Month 12
    -0.08
    (4.301)
    -0.28
    (4.166)
    42. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set Year 2 included all participants who received at least 1 dose of study drug. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Cenicriviroc 150 mg tablet or placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2.
    Measure Participants 60 182
    Baseline (Month 15)
    98.25
    (24.087)
    95.32
    (20.749)
    Change from Baseline to Month 15
    0.15
    (3.448)
    -0.44
    (4.257)
    Baseline (Month 18)
    96.98
    (22.210)
    95.23
    (20.823)
    Change from Baseline to Month 18
    0.05
    (4.194)
    -0.16
    (4.458)
    Baseline (Month 24)
    96.98
    (22.210)
    95.19
    (20.972)
    Change from Baseline to Month 24
    -0.91
    (5.649)
    -0.56
    (5.081)
    43. Secondary Outcome
    Title Change From Baseline in Body Mass Index (BMI) at Months 3, 6 and 12
    Description 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.
    Time Frame Baseline (Day 1) to Months 3, 6 and 12

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set Year 1 included all participants who received at least 1 dose of study drug. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1. Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.
    Measure Participants 144 144
    Baseline (Month 3)
    34.129
    (7.2492)
    33.706
    (5.7812)
    Change from Baseline to Month 3
    -0.172
    (0.9200)
    -0.232
    (0.9500)
    Baseline (Month 6)
    34.196
    (7.3086)
    33.547
    (5.6037)
    Change from Baseline to Month 6
    -0.182
    (1.1558)
    -0.196
    (1.2500)
    Baseline (Month 12)
    34.029
    (7.1358)
    33.374
    (5.6631)
    Change from Baseline to Month 12
    -0.013
    (1.7507)
    -0.145
    (1.4891)
    44. Secondary Outcome
    Title Change From Baseline in Body Mass Index (BMI) at Months 15, 18 and 24
    Description 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.
    Time Frame Baseline (Day 1) to Months 15, 18 and 24

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set Year 2 included all participants who received at least 1 dose of study drug. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Cenicriviroc 150 mg tablet or placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2.
    Measure Participants 60 182
    Baseline (Month 15)
    34.713
    (8.0431)
    33.392
    (5.9669)
    Change from Baseline to Month 15
    -0.006
    (1.2799)
    -0.113
    (1.6311)
    Baseline (Month 18)
    34.473
    (7.8964)
    33.345
    (5.9443)
    Change from Baseline to Month 18
    -0.039
    (1.5931)
    -0.040
    (1.7153)
    Baseline (Month 24)
    34.473
    (7.8964)
    33.278
    (6.0012)
    Change from Baseline to Month 24
    -0.393
    (2.0613)
    -0.178
    (1.8515)
    45. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set Year 1 included all participants who received at least 1 dose of study drug. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1. Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.
    Measure Participants 144 144
    Baseline (Month 3)
    110.35
    (14.866)
    110.25
    (13.406)
    Change from Baseline to Month 3
    0.07
    (5.147)
    0.05
    (5.396)
    Baseline (Month 6)
    110.42
    (14.986)
    110.12
    (13.561)
    Change from Baseline to Month 6
    0.42
    (8.827)
    -0.54
    (5.876)
    Baseline (Month 12)
    109.77
    (14.617)
    110.02
    (13.711)
    Change from Baseline to Month 12
    0.44
    (6.584)
    -1.10
    (6.255)
    46. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set Year 2 included all participants who received at least 1 dose of study drug. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Cenicriviroc 150 mg tablet or placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2.
    Measure Participants 60 182
    Baseline (Month 15)
    110.19
    (14.360)
    110.26
    (14.486)
    Change from Baseline to Month 15
    0.52
    (5.520)
    -0.18
    (6.280)
    Baseline (Month 18)
    109.48
    (12.703)
    110.25
    (14.517)
    Change from Baseline to Month 18
    1.36
    (7.966)
    -0.21
    (6.578)
    Baseline (Month 24)
    109.36
    (12.608)
    110.08
    (14.606)
    Change from Baseline to Month 24
    0.11
    (7.907)
    -1.00
    (6.503)
    47. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set Year 1 included all participants who received at least 1 dose of study drug. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1. Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.
    Measure Participants 144 144
    Baseline (Month 3)
    114.92
    (16.150)
    112.35
    (13.802)
    Change from Baseline to Month 3
    -0.30
    (4.921)
    -0.11
    (6.475)
    Baseline (Month 6)
    115.09
    (16.270)
    112.16
    (13.320)
    Change from Baseline to Month 6
    -0.84
    (4.396)
    -0.18
    (5.715)
    Baseline (Month 12)
    114.46
    (15.970)
    111.66
    (13.376)
    Change from Baseline to Month 12
    -0.25
    (5.876)
    -0.08
    (7.474)
    48. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set Year 2 included all participants who received at least 1 dose of study drug. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Cenicriviroc 150 mg tablet or placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2.
    Measure Participants 60 182
    Baseline (Month 15)
    114.56
    (17.500)
    113.00
    (14.183)
    Change from Baseline to Month 15
    -0.06
    (5.361)
    -0.83
    (7.050)
    Baseline (Month 18)
    114.28
    (17.871)
    112.70
    (14.168)
    Change from Baseline to Month 18
    0.55
    (7.791)
    -0.90
    (6.066)
    Baseline (Month 24)
    114.34
    (17.408)
    112.88
    (14.225)
    Change from Baseline to Month 24
    -0.95
    (7.700)
    -1.21
    (6.677)
    49. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set Year 1 included all participants who received at least 1 dose of study drug. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1. Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.
    Measure Participants 144 144
    Baseline (Month 3)
    32.95
    (7.346)
    33.38
    (4.835)
    Change from Baseline to Month 3
    0.97
    (6.023)
    0.10
    (6.486)
    Baseline (Month 6)
    32.70
    (7.290)
    33.25
    (4.734)
    Change from Baseline to Month 6
    0.82
    (6.748)
    -0.01
    (3.447)
    Baseline (Month 12)
    32.51
    (7.277)
    33.09
    (4.771)
    Change from Baseline to Month 12
    0.83
    (6.656)
    -0.43
    (3.516)
    50. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set Year 2 included all participants who received at least 1 dose of study drug. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Cenicriviroc 150 mg tablet or placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2.
    Measure Participants 60 182
    Baseline (Month 15)
    32.88
    (7.783)
    32.91
    (5.662)
    Change from Baseline to Month 15
    1.61
    (6.534)
    0.01
    (5.052)
    Baseline (Month 18)
    32.63
    (7.718)
    32.87
    (5.696)
    Change from Baseline to Month 18
    1.79
    (6.715)
    0.02
    (4.709)
    Baseline (Month 24)
    32.79
    (7.660)
    33.02
    (5.561)
    Change from Baseline to Month 24
    0.78
    (6.124)
    -0.64
    (4.408)
    51. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set Year 1 included all participants who received at least 1 dose of study drug. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1. Cenicriviroc 150 mg tablet, once daily in the morning with food in Year 1.
    Measure Participants 144 144
    Baseline (Month 3)
    28.32
    (13.677)
    25.41
    (12.593)
    Change from Baseline to Month 3
    -1.21
    (6.548)
    -0.62
    (8.704)
    Baseline (Month 6)
    28.53
    (13.763)
    25.38
    (12.769)
    Change from Baseline to Month 6
    -2.72
    (8.091)
    -1.52
    (9.287)
    Baseline (Month 12)
    28.54
    (13.981)
    25.14
    (12.969)
    Change from Baseline to Month 12
    -1.34
    (9.389)
    -0.26
    (10.653)
    52. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set Year 2 included all participants who received at least 1 dose of study drug. Number analyzed is the number of participants with data available for analysis at both Baseline and the given time-point.
    Arm/Group Title Placebo CVC 150 mg
    Arm/Group Description Placebo-matching cenicriviroc tablet, once daily in the morning with food in Years 1 and 2. Cenicriviroc 150 mg tablet or placebo-matching cenicriviroc tablet, once daily in the morning with food in Year 1 then cenicriviroc 150 mg tablet, once daily in the morning with food in Year 2.
    Measure Participants 60 182
    Baseline (Month 15)
    29.84
    (14.422)
    25.41
    (13.212)
    Change from Baseline to Month 15
    -1.45
    (9.364)
    -1.59
    (8.918)
    Baseline (Month 18)
    29.84
    (14.655)
    25.07
    (12.856)
    Change from Baseline to Month 18
    -2.27
    (8.854)
    -2.64
    (8.864)
    Baseline (Month 24)
    29.91
    (14.532)
    24.82
    (13.025)
    Change from Baseline to Month 24
    -3.11
    (8.553)
    -1.33
    (10.521)

    Adverse Events

    Time Frame Baseline to Year 2
    Adverse Event Reporting Description Safety Analysis Set Year 1 and Year 2 included all participants who received at least 1 dose of study drug.
    Arm/Group Title CVC 150mg/CVC 150 mg Placebo/Cenicriviroc (CVC) 150 mg Placebo/Placebo
    Arm/Group Description CVC 150 mg tablet, once daily in the morning with food in Years 1 and 2. Placebo-matching CVC tablet, once daily in the morning with food in Year 1 then CVC 150 mg tablet, once daily in the morning with food in Year 2. Placebo-matching cenicriviroc (CVC) tablet, once daily in the morning with food in Years 1 and 2.
    All Cause Mortality
    CVC 150mg/CVC 150 mg Placebo/Cenicriviroc (CVC) 150 mg Placebo/Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/144 (0%) 0/72 (0%) 0/72 (0%)
    Serious Adverse Events
    CVC 150mg/CVC 150 mg Placebo/Cenicriviroc (CVC) 150 mg Placebo/Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 25/144 (17.4%) 8/72 (11.1%) 12/72 (16.7%)
    Blood and lymphatic system disorders
    Anaemia 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Cardiac disorders
    Acute coronary syndrome 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Acute myocardial infarction 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Arrhythmia 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Cardiac failure congestive 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Coronary artery occlusion 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Myocardial ischaemia 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Gastrointestinal disorders
    Inguinal hernia 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Pancreatitis acute 0/144 (0%) 0/72 (0%) 1/72 (1.4%)
    Abdominal pain upper 0/144 (0%) 1/72 (1.4%) 0/72 (0%)
    Colitis ischaemic 0/144 (0%) 0/72 (0%) 1/72 (1.4%)
    Large intestine polyp 0/144 (0%) 0/72 (0%) 1/72 (1.4%)
    Peritoneal haemorrhage 0/144 (0%) 0/72 (0%) 1/72 (1.4%)
    Vasculitis gastrointestinal 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    General disorders
    Chest pain 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Non-cardiac chest pain 2/144 (1.4%) 0/72 (0%) 1/72 (1.4%)
    Hepatobiliary disorders
    Cholelithiasis 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Infections and infestations
    Appendicitis 0/144 (0%) 1/72 (1.4%) 0/72 (0%)
    Cellulitis 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Diverticulitis 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Gastroenteritis 0/144 (0%) 0/72 (0%) 1/72 (1.4%)
    Pneumonia 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Sepsis 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Pyelonephritis 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Subcutaneous abscess 0/144 (0%) 0/72 (0%) 1/72 (1.4%)
    Urosepsis 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Injury, poisoning and procedural complications
    Accidental overdose 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Ankle fracture 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Concussion 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Facial bones fracture 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Joint injury 0/144 (0%) 1/72 (1.4%) 0/72 (0%)
    Laceration 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Lumbar vertebral fracture 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Meniscus injury 0/144 (0%) 1/72 (1.4%) 0/72 (0%)
    Traumatic haemothorax 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Humerus fracture 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Overdose 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Procedural pain 0/144 (0%) 1/72 (1.4%) 0/72 (0%)
    Wrist fracture 0/144 (0%) 0/72 (0%) 1/72 (1.4%)
    Investigations
    Blood triglycerides increased 0/144 (0%) 0/72 (0%) 1/72 (1.4%)
    Metabolism and nutrition disorders
    Dehydration 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Type 2 diabetes mellitus 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Hypovolaemia 0/144 (0%) 0/72 (0%) 1/72 (1.4%)
    Musculoskeletal and connective tissue disorders
    Back pain 0/144 (0%) 0/72 (0%) 1/72 (1.4%)
    Spinal osteoarthritis 0/144 (0%) 0/72 (0%) 1/72 (1.4%)
    Osteoarthritis 2/144 (1.4%) 0/72 (0%) 0/72 (0%)
    Intervertebral disc protrusion 0/144 (0%) 0/72 (0%) 1/72 (1.4%)
    Lumbar spinal stenosis 0/144 (0%) 0/72 (0%) 1/72 (1.4%)
    Psoriatic arthropathy 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Pancreatic neoplasm 0/144 (0%) 1/72 (1.4%) 0/72 (0%)
    Peripheral nerve sheath tumour malignant 0/144 (0%) 1/72 (1.4%) 0/72 (0%)
    Haemangioma of skin 0/144 (0%) 1/72 (1.4%) 0/72 (0%)
    Nervous system disorders
    Convulsion 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Syncope 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Generalised tonic-clonic seizure 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Loss of consciousness 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Paraesthesia 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    VIIth nerve paralysis 0/144 (0%) 0/72 (0%) 1/72 (1.4%)
    Psychiatric disorders
    Bipolar disorder 0/144 (0%) 0/72 (0%) 1/72 (1.4%)
    Renal and urinary disorders
    Nephrolithiasis 0/144 (0%) 1/72 (1.4%) 0/72 (0%)
    Renal failure 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Renal failure acute 0/144 (0%) 1/72 (1.4%) 1/72 (1.4%)
    Bladder dysplasia 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Lung disorder 1/144 (0.7%) 0/72 (0%) 0/72 (0%)
    Asthma 0/144 (0%) 0/72 (0%) 1/72 (1.4%)
    Vascular disorders
    Deep vein thrombosis 0/144 (0%) 0/72 (0%) 1/72 (1.4%)
    Other (Not Including Serious) Adverse Events
    CVC 150mg/CVC 150 mg Placebo/Cenicriviroc (CVC) 150 mg Placebo/Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 127/144 (88.2%) 59/72 (81.9%) 60/72 (83.3%)
    Gastrointestinal disorders
    Diarrhoea 32/144 (22.2%) 14/72 (19.4%) 15/72 (20.8%)
    Abdominal pain upper 16/144 (11.1%) 12/72 (16.7%) 10/72 (13.9%)
    Abdominal pain 18/144 (12.5%) 6/72 (8.3%) 11/72 (15.3%)
    Nausea 28/144 (19.4%) 6/72 (8.3%) 8/72 (11.1%)
    Abdominal distension 13/144 (9%) 4/72 (5.6%) 0/72 (0%)
    Constipation 13/144 (9%) 4/72 (5.6%) 6/72 (8.3%)
    Flatulence 9/144 (6.3%) 3/72 (4.2%) 2/72 (2.8%)
    Gastrooesophageal reflux disease 6/144 (4.2%) 3/72 (4.2%) 4/72 (5.6%)
    Vomiting 18/144 (12.5%) 3/72 (4.2%) 5/72 (6.9%)
    General disorders
    Fatigue 24/144 (16.7%) 10/72 (13.9%) 13/72 (18.1%)
    Oedema peripheral 5/144 (3.5%) 5/72 (6.9%) 3/72 (4.2%)
    Pyrexia 8/144 (5.6%) 4/72 (5.6%) 1/72 (1.4%)
    Infections and infestations
    Urinary tract infection 17/144 (11.8%) 10/72 (13.9%) 4/72 (5.6%)
    Nasopharyngitis 21/144 (14.6%) 9/72 (12.5%) 7/72 (9.7%)
    Upper respiratory tract infection 18/144 (12.5%) 9/72 (12.5%) 8/72 (11.1%)
    Influenza 11/144 (7.6%) 3/72 (4.2%) 3/72 (4.2%)
    Sinusitis 18/144 (12.5%) 3/72 (4.2%) 9/72 (12.5%)
    Ear infection 5/144 (3.5%) 2/72 (2.8%) 4/72 (5.6%)
    Bronchitis 10/144 (6.9%) 1/72 (1.4%) 7/72 (9.7%)
    Gastroenteritis 3/144 (2.1%) 1/72 (1.4%) 4/72 (5.6%)
    Injury, poisoning and procedural complications
    Procedural pain 5/144 (3.5%) 2/72 (2.8%) 9/72 (12.5%)
    Investigations
    Alanine aminotransferase increased 15/144 (10.4%) 9/72 (12.5%) 5/72 (6.9%)
    Blood creatine phosphokinase increased 3/144 (2.1%) 5/72 (6.9%) 0/72 (0%)
    Metabolism and nutrition disorders
    Type 2 diabetes mellitus 6/144 (4.2%) 5/72 (6.9%) 4/72 (5.6%)
    Hyperglycaemia 0/144 (0%) 4/72 (5.6%) 2/72 (2.8%)
    Musculoskeletal and connective tissue disorders
    Back pain 11/144 (7.6%) 11/72 (15.3%) 12/72 (16.7%)
    Myalgia 11/144 (7.6%) 5/72 (6.9%) 3/72 (4.2%)
    Arthralgia 23/144 (16%) 4/72 (5.6%) 4/72 (5.6%)
    Muscle spasms 15/144 (10.4%) 4/72 (5.6%) 2/72 (2.8%)
    Pain in extremity 14/144 (9.7%) 1/72 (1.4%) 6/72 (8.3%)
    Nervous system disorders
    Headache 24/144 (16.7%) 15/72 (20.8%) 9/72 (12.5%)
    Dizziness 13/144 (9%) 0/72 (0%) 5/72 (6.9%)
    Psychiatric disorders
    Insomnia 10/144 (6.9%) 2/72 (2.8%) 2/72 (2.8%)
    Respiratory, thoracic and mediastinal disorders
    Cough 16/144 (11.1%) 5/72 (6.9%) 6/72 (8.3%)
    Oropharyngeal pain 13/144 (9%) 3/72 (4.2%) 4/72 (5.6%)
    Nasal congestion 8/144 (5.6%) 0/72 (0%) 2/72 (2.8%)
    Skin and subcutaneous tissue disorders
    Pruritus 10/144 (6.9%) 3/72 (4.2%) 5/72 (6.9%)
    Rash 12/144 (8.3%) 3/72 (4.2%) 8/72 (11.1%)
    Vascular disorders
    Hypertension 10/144 (6.9%) 4/72 (5.6%) 3/72 (4.2%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Therapeutic Area, Head
    Organization Allergan
    Phone 714-246-4500
    Email clinicaltrials@allergan.com
    Responsible Party:
    Tobira Therapeutics, Inc.
    ClinicalTrials.gov Identifier:
    NCT02217475
    Other Study ID Numbers:
    • 652-2-203
    • 2016-004754-15
    First Posted:
    Aug 15, 2014
    Last Update Posted:
    May 10, 2019
    Last Verified:
    Mar 1, 2019