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Nonalcoholic SteatohepatitisPhase 2CENTAURNCT02217475

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

A Phase 2 study testing Cenicriviroc in people with Nonalcoholic Steatohepatitis, run by Tobira Therapeutics, Inc. at 91 sites in 10 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Nonalcoholic Steatohepatitis
What is being tested?
Cenicriviroc
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
289 participants
Where
91 sitesin 10 countries
Study dates
18 Sep 2014to 22 Jun 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adult participants aged between 18-75
  • Histological evidence of NASH, based on biopsy, with a Nonalcoholic fatty liver disease Activity Score (NAS) of >= 4 with at least 1 in each component of NAS
  • Histological evidence of liver fibrosis defined as NASH Clinical Research Network (CRN) System Stage 1 to 3
  • Meeting any of the 3 major criteria (a, b, c):
  • Documented evidence of type 2 diabetes mellitus
  • High body mass index (> 25 kg/m^2) with at least one of the following criteria of metabolic syndrome, as defined by the National Cholesterol Education Program:
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  • Central obesity: waist circumference ≥ 102 cm or 40 inches (male), ≥ 88 cm or 35 inches (female)
  • Dyslipidemia: Triglycerides ≥ 1.7 mmol/L (150 mg/dL)
  • Dyslipidemia: High-density lipoprotein (HDL)-cholesterol < 40 mg/dL (male), < 50 mg/dL (female)
  • Blood pressure ≥ 130/85 mmHg (or currently being treated for hypertension)
  • Fasting plasma glucose ≥ 6.1 mmol/L (110 mg/dL)
  • Bridging fibrosis (NASH CRN Stage 3) and/or definite NASH (NAS ≥ 5)
  • Agree to have one liver biopsy at Screening, one at Year 1, and one at the end of study treatment (Year 2)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × upper limit of normal (ULN)

Who cannot join

  • Hepatitis B surface Antigen (HBsAg) positive
  • Hepatitis C antibody (HCVAb) positive with the following 2 exceptions:
  • Participants previously treated for viral hepatitis C with at least a 1-year period since documented sustained virologic response at Week 12 (post-treatment) may be eligible if all other eligibility criteria are met
  • Participants with presence of hepatitis C antibody but negative hepatitis C virus ribonucleic acid RNA without treatment (i.e., spontaneous clearance) may be eligible if all other eligibility criteria are met
  • Prior or planned liver transplantation
  • Other known causes of chronic liver disease, including alcoholic liver disease
Show all 12Show fewer
  • 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.

Trial locations and contacts

91 sites in 10 countries.

91 sites in 10 countries

United States40 sites

  • Study site

    Ann Arbor, Michigan, 48109

  • Study site

    Baltimore, Maryland, 21202

  • Study site

    Baltimore, Maryland, 21287

  • Study site

    Boston, Massachusetts, 02114

  • Study site

    Buffalo, New York, 14201

  • Study site

    Chattanooga, Tennessee, 37421

  • Study site

    Chevy Chase, Maryland, 20815

  • Study site

    Chicago, Illinois, 60612

  • Study site

    Cincinnati, Ohio, 45249

  • Study site

    Dothan, Alabama, 36305

  • Study site

    Durham, North Carolina, 27710

  • Study site

    Flowood, Mississippi, 39232

  • Study site

    Germantown, Tennessee, 38138

  • Study site

    Houston, Texas, 77030

  • Study site

    Houston, Texas, 78234

  • Study site

    Jackson, Mississippi

  • Study site

    Littleton, Colorado, 80120

  • Study site

    Live Oak, Texas, 78233

  • Study site

    Louisville, Kentucky, 40202

  • Study site

    Lutherville, Maryland, 21093

  • Study site

    Miami, Florida, 33136

  • Study site

    New Orleans, Louisiana, 70112

  • Study site

    New York, New York, 10029

  • Study site

    Phoenix, Arizona, 85054

  • Study site

    Raleigh, North Carolina, 27612

  • Study site

    Rialto, California, 92377

  • Study site

    Richmond, Virginia, 23298

  • Study site

    Saint Paul, Minnesota, 55114

  • Study site

    Salt Lake City, Utah, 84132

  • Study site

    San Antonio, Texas, 78215

  • Study site

    San Antonio, Texas, 78233

  • Study site

    San Diego, California, 92120

  • Study site

    San Diego, California, 92161

  • Study site

    San Francisco, California, 94115

  • Study site

    Seattle, Washington, 98104

  • Study site

    Tampa, Florida, 33606

  • Study site

    Tucson, Arizona, 85712

  • Study site

    Tupelo, Mississippi, 38801

  • Study site

    Winston-Salem, North Carolina, 27103

  • Study site

    Worcester, Massachusetts, 01655

Other trials in United States

Germany10 sites

  • Study site

    Aachen, North Rhine-Westphalia, 52074

  • Study site

    Berlin, 13353

  • Study site

    Cologne, North Rhine-Westphalia, 50937

  • Study site

    Hamburg, Free and Hanseatic City of Hamburg, 20246

  • Study site

    Hanover, Lower Saxony, 30625

  • Study site

    Heidelberg, Baden-Wurttemberg, 69120

  • Study site

    Heidelberg, VIC, 3084

  • Study site

    Leipzig, Saxony, 04103

  • Study site

    Lübeck, 23538

  • Study site

    Marburg, Hesse, 35043

Other trials in Germany

France9 sites

  • Study site

    Angers, 49100

  • Study site

    Lyon, 69317

  • Study site

    Montpellier, 34295

  • Study site

    Paris, 75012

  • Study site

    Paris, 75651

  • Study site

    Pessac, 33604

  • Study site

    Toulouse, 31059

  • Study site

    Vandœuvre-lès-Nancy, 54500

  • Study site

    Villejuif, 94800

Other trials in France

Australia8 sites

  • Study site

    Adelaide, South Australia, 5000

  • Study site

    Bedford Park, South Australia, 5042

  • Study site

    Clayton, Victoria, 3168

  • Study site

    Garran, Australian Capital Territory, 2605

  • Study site

    Heidelberg, Victoria, 3084

  • Study site

    Herston, Queensland, 4029

  • Study site

    Melbourne, Victoria, 3004

  • Study site

    Perth, Western Australia, 6000

Other trials in Australia

Poland5 sites

  • Study site

    Chorzów, 41-500

  • Study site

    Lodz, 91-347

  • Study site

    Mysłowice, 41-500

  • Study site

    Rzeszów, 35-055

  • Study site

    Wroclaw, 50-349

Other trials in Poland

Spain5 sites

  • Study site

    Alicante, 03010

  • Study site

    Barcelona, 08026

  • Study site

    Barcelona, 08035

  • Study site

    Barcelona, 08036

  • Study site

    Madrid, 28007

Other trials in Spain

United Kingdom5 sites

  • Study site

    London, E1 1BB

  • Study site

    London, NW3 2QR

  • Study site

    Newcastle, NE7 7ND

  • Study site

    Nottingham, NG7 2UH

  • Study site

    Portsmouth, Hampshire, PO6 3LY

Other trials in United Kingdom

Belgium4 sites

  • Study site

    Brussels, 1070

  • Study site

    Brussels, 1200

  • Study site

    Edegem, 2650

  • Study site

    Leuven, 3000

Other trials in Belgium

Italy4 sites

  • Study site

    Bologna, BO, 40138

  • Study site

    Milan, MI, 20122

  • Study site

    Palermo, PA, 90127

  • Study site

    Rozzano, MI, 20089

Other trials in Italy

Hong Kong1 site

  • Study site

    Shatin, New Territories

Other trials in Hong Kong

About this study

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

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.

Being tested
Cenicriviroc, Placebo
Medical subject headings
Non-alcoholic Fatty Liver Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CenicrivirocDrug

    Also called TBR-652

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

  • PlaceboDrug

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

Study groups in NCT02217475
Study groupRoleWhat they receive
Cenicriviroc (CVC) 150mg/CVC 150 mgExperimentalCVC 150 mg tablet in Years 1 and 2.
Receives: Drug: Cenicriviroc
Placebo/CVC 150 mgExperimentalPlacebo-matching CVC tablet in Year 1 then CVC 150 mg tablet in Year 2.
Receives: Drug: Cenicriviroc; Drug: Placebo
Placebo/PlaceboPlacebo comparatorPlacebo-matching cenicriviroc (CVC) tablet in Years 1 and 2.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    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.

    Measured: Year 1

Secondary outcomes (51)

  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

    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.

    Measured: Year 1

  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

    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.

    Measured: Year 2

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

    Complete resolution of steatohepatitis was defined as histopathologic interpretation of no fatty liver disease, or simple or isolated steatosis with no steatohepatitis. As per NASH CRN system, no worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade. The evaluation of fibrosis stage associated with NASH was based on the NASH CRN fibrosis staging system which was scaled from 0 to 4 stages where, 0=None to 4=Cirrhosis.

    Measured: Year 1

  4. Number of Participants With Complete Resolution of Steatohepatitis With no Concurrent Worsening of Fibrosis Stage at 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.

    Measured: Year 2

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

    The evaluation of fibrosis stage associated with NASH was based on the NASH CRN Fibrosis Staging System which was scaled from 0 to 4 stages where, 0=None to 4=Cirrhosis. As per NASH CRN system, no worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade.

    Measured: Year 1

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

    Measured: Year 2

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

    A TEAE was defined as any adverse event that started or worsened on or after the start of the study medication and up to 30 days after the discontinuation of the study medication. An SAE was defined as any untoward medical occurrence that, at any dose, results in death, was life threatening, requires hospitalization or results in prolongation of existing hospitalization, results in disability/incapacity, or was a congenital anomaly/birth defect.

    Measured: Years 1 and 2

  8. Number of Participants With Clinically Significant Changes in Vital Signs

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

    Measured: Years 1 and 2

  9. Number of Participants With Clinical Laboratory Abnormalities

    Grade 3-4 abnormal clinical laboratory values that occurred in ≥2% participants were reported. Criteria used for various parameters was:Fasting glucose Grade3:>250 - 500 mg/dL and Grade4: >500 mg/dL; Alanine aminotransferase(ALT)Grade3:>5.0 - 20.0 ×Upper Limit of Normal(ULN)and Grade4:>20.0 ×ULN; Aspartate aminotransferase(AST)Grade3: >5.0 - 20.0 ×ULN and Grade4: >20.0 ×ULN; Activated partial thromboplastin(APT)/Partial thromboplastin time(PTT)Grade3: >2.5×ULN; Triglycerides Grade3 >500 - 1000 mg/dL and Grade4: >1000 mg/dL; Gamma-glutamyl transferase(GGT)Grade3: >5.0 - 20.0 ×ULN and Grade4: >20.0 ×ULN; Creatine kinase Grade 3: >5.0 - 10.0 ×ULN and Grade4: >10.0 ×ULN; Uric acid Grade3:(ULN - 10 mg/dL; ULN - 0.59 mmol/L) and Grade4: >10 mg/dL; Amylase Grade3: >2.0 - 5.0 ×ULN and Grade4: >5.0 ×ULN; Lipase Grade3: >2.0 - 5.0 xULN and Grade4: >5.0 xULN; Phosphorus Grade3: <2.0 - 1.0 mg/dL and Grade4: <1.0 mg/dL and Absolute neutrophil Grade3: <1.0 - 0.5 × 109/L and Grade4: <0.5 × 109/L.

    Measured: Years 1 and 2

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

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

    Measured: Years 1 and 2

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

    Hepatic histological improvement in NAS at Year 2 was defined as a decrease (improvement) in NAS by ≥ 2 with at least a 1-point reduction in either lobular inflammation or hepatocellular ballooning and with no concurrent worsening of fibrosis stage. The NAS was derived as the unweighted sum of steatosis (0 to 3), lobular inflammation (0 to 3), and hepatocellular ballooning (0 to 2) scores. The NAS ranges from 0-8 with the higher score indicating more aggressive disease.

    Measured: Year 2

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

    NAS was calculated using the following 3 categorical features: steatosis which was scaled from 0-3 (steatosis score is defined as 0= <5%, 1= 5 - 33%, 2= >33 - 66%, and 3= >66%), lobular inflammation which was scaled from 0-3 (lobular inflammation score defined as 0= no foci, 1= < 2 foci/200x, 2= 2-4 foci/200x, and 3= > 4 foci/200x), and hepatocellular ballooning which was scaled from 0-2 (hepatocellular ballooning score is defined as 0=none, 1=few balloon cells, 2=many cells/prominent ballooning). A negative change from Baseline indicates improvement.

    Measured: Year 1

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

    Measured: Year 2

  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

    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.

    Measured: Year 1

  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

    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.

    Measured: Year 2

  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

    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).

    Measured: Year 1

  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

    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).

    Measured: Year 2

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

    The morphometric quantitative collagen on liver biopsy was determined as percent collagen area (PCA) using Sirius red stain on liver biopsy at Year 1. A negative change from Baseline indicates improvement.

    Measured: Year 1

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

    The morphometric quantitative collagen on liver biopsy was determined as percent collagen area (PCA) using Sirius red stain on liver biopsy at Year 2. A negative change from Baseline indicates improvement.

    Measured: Year 2

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

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

    Measured: Baseline (Day 1) to Year 1

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

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

    Measured: Baseline (Day 1) to Year 2

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

    The morphometric quantitative fat content was done to find out the amount of fat accumulated in the liver. A liver biopsy was performed to determine percent fat area, at Year 1. A negative change from Baseline indicates improvement.

    Measured: Year 1

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

    The morphometric quantitative fat content was done to find out the amount of fat accumulated in the liver. A liver biopsy was performed to determine percent fat area, at Year 2. A negative change from Baseline indicates improvement.

    Measured: Year 2

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

    The participant's histologic fibrosis stage was determined using the NASH CRN system and Ishak scale score assessment at Year 1. The evaluation of fibrosis stage associated with NASH was based on the NASH CRN Fibrosis Staging System which was scaled from 0 to 4 where, 0=None to 4=Cirrhosis. The histologic fibrosis stage based on the Ishak assessment was divided into 1 to 6 stages. Fibrosis was staged with the Ishak scale (ranging from 0=No fibrosis to 6=Cirrhosis). A positive change from Baseline indicates worsening.

    Measured: Baseline (Day 1) to Year 1

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

    Measured: Baseline (Day 1) to Year 2

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

    Portal inflammation on liver biopsy was graded from 0 to 4 where 0= None, 1= Mild, 2= Moderate, and 3= Marked. A positive change from Baseline indicates worsening.

    Measured: Baseline (Day 1) to Year 1

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

    Portal inflammation on liver biopsy was graded from 0 to 4 where 0= None, 1= Mild, 2= Moderate, and 3= Marked. A positive change from Baseline indicates worsening.

    Measured: Baseline (Day 1) to Year 2

  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

    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.

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

  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

    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.

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

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

    Fibrosis-4 is the ratio of age in years and aminotransferase to platelet count. It is a non-invasive hepatic fibrosis index score combining standard biochemical values, platelets, alanine aminotransferase (ALT), AST and age that is calculated using formula: FIB-4 = (Age [years] x AST [U/L]) / (platelets [10^9/L] x (square root of ALT [U/L])). A FIB-4 index of < 1.45 indicated no or moderate fibrosis and an index of > 3.25 indicated extensive fibrosis/cirrhosis. A positive change from Baseline indicates increased fibrosis.

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

  31. Change From Baseline in Non-invasive Marker of Hepatic Fibrosis: Fibrosis-4 (FIB-4) at 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.

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

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

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

    Measured: Baseline (Month 0) to Months 6 and 12

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

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

    Measured: Baseline (Month 0) to Months 18 and 24

  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

    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.

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

  35. Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: NAFLD Fibrosis Score (NFS) at 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.

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

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

    The markers of fibrosis assessed in this test comprised hyaluronic acid (CHA), tissue inhibitor of metalloproteinase (CTIMP1) and procollagen III N-terminal peptide (CP3NP); these are components of the extracellular matrix and basement sinusoidal membrane of the liver and are elevated during activation of the stellate cell. The ELF tests were performed on Centaur device and the composite score was calculated as follows: ELF score = 2.278 + 0.851 ln(CHA) + 0.751 ln (CP3NP) + 0.394 ln(CTIMP1). ELF score < 7.7: no to mild fibrosis; ≥ 7.7 - < 9.8: Moderate fibrosis; ≥ 9.8 - < 11.3: Severe fibrosis; ≥ 11.3: Cirrhosis. A negative change from Baseline indicates decreased fibrosis.

    Measured: Baseline (Month 0) to Months 6 and 12

  37. Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at 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.

    Measured: Baseline (Month 0) to Months 18 and 24

  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

    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.

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

  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

    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.

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

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

    A negative change from Baseline represents decreased weight.

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

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

    A negative change from Baseline represents decreased weight.

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

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

    The body mass index is a value derived from the mass (weight in kgs) and height (in centimeters) of an individual and is calculated as the body mass divided by the square of the body height. A negative change from Baseline represents decreased BMI.

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

  43. Change From Baseline in Body Mass Index (BMI) at 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.

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

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

    A negative change from Baseline represents decreased in waist circumference.

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

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

    A negative change from Baseline represents decreased in waist circumference.

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

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

    A negative change from Baseline represents decreased hip circumference.

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

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

    A negative change from Baseline represents decreased hip circumference.

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

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

    A negative change from Baseline represents decreased forearm circumference.

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

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

    A negative change from Baseline represents decreased forearm circumference.

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

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

    A negative change from Baseline represents decreased Tricep Skinfold Thickness.

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

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

    A negative change from Baseline represents decreased Tricep Skinfold Thickness.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Aug 2014 (estimated)
  2. Study start18 Sep 2014
  3. Primary completion30 Jun 2016
  4. Study completion22 Jun 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
289 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02217475
Sponsor's protocol ID
652-2-203
Other IDs
2016-004754-15, 2016
Acronym
CENTAUR
Status last verified
Mar 2019
First submitted
13 Aug 2014
Last updated
10 May 2019
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

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

    PubMed 34951993

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

    PubMed 34454994

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

    PubMed 33666272

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

    PubMed 31943293

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

    PubMed 27347680

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

    PubMed 26944023

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cenicriviroc in people with Nonalcoholic Steatohepatitis, run by Tobira Therapeutics, Inc. at 91 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 91 sites in United States, Germany, France, Australia, Poland and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: Year 1). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02217475, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2019; AzTrials last refreshed its copy on 8 Nov 2026.

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