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

NCT02217475 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 652-2-2032016-004754-15
• Study Type: interventional
• Target: 289
• Locations: 10 countries
• Sites: 91

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.

Conditions

Nonalcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (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.

  Year 1

Secondary Outcomes (51)

• 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

• 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

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

  Year 1

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

  Year 2

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

  Year 1

Study Arms (3)

Cenicriviroc (CVC) 150mg/CVC 150 mg

EXPERIMENTAL

CVC 150 mg tablet in Years 1 and 2.

Drug: Cenicriviroc

Placebo/CVC 150 mg

EXPERIMENTAL

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

Drug: Cenicriviroc; Drug: Placebo

Placebo/Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Cenicriviroc DRUG

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

Also known as: TBR-652

Cenicriviroc (CVC) 150mg/CVC 150 mg; Placebo/CVC 150 mg

Placebo DRUG

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

Placebo/CVC 150 mg; Placebo/Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Hepatitis B surface Antigen (HBsAg) positive
• Hepatitis C antibody (HCVAb) positive with the following 2 exceptions:
• Participants previously treated for viral hepatitis C with at least a 1-year period since documented sustained virologic response at Week 12 (post-treatment) may be eligible if all other eligibility criteria are met
• Participants with presence of hepatitis C antibody but negative hepatitis C virus ribonucleic acid RNA without treatment (i.e., spontaneous clearance) may be eligible if all other eligibility criteria are met
• Prior or planned liver transplantation
• Other known causes of chronic liver disease, including alcoholic liver disease
• History of cirrhosis and/or hepatic decompensation including ascites, hepatic encephalopathy or variceal bleeding
• Alcohol consumption greater than 21 units/week for males or 14 units/week for females (one unit of alcohol is ½ pint of beer \[285 mL\], 1 glass of spirits \[25 mL\] or 1 glass of wine \[125 mL\])
• Human immunodeficiency virus (HIV)-1 or HIV-2 infection
• Weight reduction through bariatric surgery in the past 5 years or planned during the conduct of the study (including gastric banding)
• Females who are pregnant or breastfeeding
• Any other clinically significant disorders or prior therapy that, in the opinion of the investigator, would make the participant unsuitable for the study or unable to comply with the dosing and protocol requirements.

Sponsors & Collaborators

• Tobira Therapeutics, Inc.: lead

Study Sites (91)

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Dothan, Alabama, 36305, United States

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Phoenix, Arizona, 85054, United States

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Tucson, Arizona, 85712, United States

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Rialto, California, 92377, United States

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San Diego, California, 92120, United States

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San Diego, California, 92161, United States

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San Francisco, California, 94115, United States

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Littleton, Colorado, 80120, United States

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Miami, Florida, 33136, United States

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Tampa, Florida, 33606, United States

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Chicago, Illinois, 60612, United States

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Louisville, Kentucky, 40202, United States

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New Orleans, Louisiana, 70112, United States

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Baltimore, Maryland, 21202, United States

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Baltimore, Maryland, 21287, United States

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Chevy Chase, Maryland, 20815, United States

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Lutherville, Maryland, 21093, United States

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Boston, Massachusetts, 02114, United States

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Worcester, Massachusetts, 01655, United States

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Ann Arbor, Michigan, 48109, United States

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Saint Paul, Minnesota, 55114, United States

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Flowood, Mississippi, 39232, United States

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Jackson, Mississippi, United States

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Tupelo, Mississippi, 38801, United States

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Buffalo, New York, 14201, United States

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New York, New York, 10029, United States

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Durham, North Carolina, 27710, United States

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Raleigh, North Carolina, 27612, United States

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Winston-Salem, North Carolina, 27103, United States

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Cincinnati, Ohio, 45249, United States

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Chattanooga, Tennessee, 37421, United States

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Germantown, Tennessee, 38138, United States

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Houston, Texas, 77030, United States

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Houston, Texas, 78234, United States

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Live Oak, Texas, 78233, United States

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San Antonio, Texas, 78215, United States

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San Antonio, Texas, 78233, United States

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Salt Lake City, Utah, 84132, United States

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Richmond, Virginia, 23298, United States

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Seattle, Washington, 98104, United States

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Garran, Australian Capital Territory, 2605, Australia

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Herston, Queensland, 4029, Australia

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Adelaide, South Australia, 5000, Australia

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Bedford Park, South Australia, 5042, Australia

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Clayton, Victoria, 3168, Australia

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Heidelberg, Victoria, 3084, Australia

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Melbourne, Victoria, 3004, Australia

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Perth, Western Australia, 6000, Australia

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Brussels, 1070, Belgium

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Brussels, 1200, Belgium

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Edegem, 2650, Belgium

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Leuven, 3000, Belgium

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Angers, 49100, France

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Lyon, 69317, France

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Montpellier, 34295, France

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Paris, 75012, France

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Paris, 75651, France

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Pessac, 33604, France

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Toulouse, 31059, France

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Vandœuvre-lès-Nancy, 54500, France

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Villejuif, 94800, France

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Heidelberg, Baden-Wurttemberg, 69120, Germany

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Hamburg, Hamburg, 20246, Germany

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Marburg, Hesse, 35043, Germany

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Hanover, Lower Saxony, 30625, Germany

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Aachen, North Rhine-Westphalia, 52074, Germany

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Cologne, North Rhine-Westphalia, 50937, Germany

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Leipzig, Saxony, 04103, Germany

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Heidelberg, VIC, 3084, Germany

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Berlin, 13353, Germany

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Lübeck, 23538, Germany

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Shatin, New Territories, Hong Kong

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Bologna, BO, 40138, Italy

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Milan, MI, 20122, Italy

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Rozzano, MI, 20089, Italy

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Palermo, PA, 90127, Italy

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Chorzów, 41-500, Poland

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Lodz, 91-347, Poland

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Mysłowice, 41-500, Poland

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Rzeszów, 35-055, Poland

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Wroclaw, 50-349, Poland

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Alicante, 03010, Spain

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Barcelona, 08026, Spain

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Barcelona, 08035, Spain

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Barcelona, 08036, Spain

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Madrid, 28007, Spain

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Portsmouth, Hampshire, PO6 3LY, United Kingdom

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London, E1 1BB, United Kingdom

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London, NW3 2QR, United Kingdom

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Newcastle, NE7 7ND, United Kingdom

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Nottingham, NG7 2UH, United Kingdom

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Related Publications (6)

• 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.

  PMID: 34951993 DERIVED

• 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.

  PMID: 34454994 DERIVED

• 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.

  PMID: 33666272 DERIVED

• 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.

  PMID: 31943293 DERIVED

• 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.

  PMID: 27347680 DERIVED

• 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.

  PMID: 26944023 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

cenicriviroc

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Therapeutic Area, Head
• Organization: Allergan

clinicaltrials@allergan.com

714-246-4500

Study Officials

• Eric Lefebvre, MD

  Allergan

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2014
• First Posted: August 15, 2014
• Study Start: September 18, 2014
• Primary Completion: June 30, 2016
• Study Completion: June 22, 2017
• Last Updated: May 10, 2019
• Results First Posted: May 10, 2019

Record last verified: 2019-03

Locations

IT (4); AU (8); FR (9); US (40); HK (1); PL (5); ES (5); DE (10); BE (4); GB (5)