The study of an investigational drug, Cenicriviroc, for the treatment of liver fibrosis in patients with Nonalcoholic Steatohepatitis (NASH).

• Register: EUCTR
• Last refreshed on: 3 November 2021
• Main ID: EUCTR2016-004566-26-PT
• Date of registration: 21/03/2017
• Prospective Registration: Yes
• Primary sponsor: Tobira Therapeutics,Inc., a subsidiary of Allergan plc
• Public title: The study of an investigational drug, Cenicriviroc, for the treatment of liver fibrosis in patients with Nonalcoholic Steatohepatitis (NASH).
• Scientific title: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Cenicriviroc for the Treatment of Liver Fibrosis in Adult Subjects with Nonalcoholic Steatohepatitis - AURORA
• Date of first enrolment: 26/06/2017
• Target sample size: 2000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004566-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, France, Germany, Greece, Hong Kong, Hungary, India, Israel, Italy, Latvia, Mauritius, Mexico, New Zealand, Norway, Peru, Poland, Portugal, Puerto Rico, Romania, Russian Federation, Singapore, Slovenia, Spain, Switzerland, Taiwan, United Kingdom, United States

Contacts

• Name: Bosco D'Sa
• Affiliation: Tobira Therapeutics Inc., a subsidiary of Allergan plc

• Name: Bosco D'Sa
• Affiliation: Tobira Therapeutics Inc., a subsidiary of Allergan plc

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male and female subjects aged between 18-75 years
2. Ability to understand and sign a written informed consent form (ICF)
3. Histological evidence of NASH based on central reading of the screening liver biopsy slides
4. Subjects included in Part1 must have histopathological evidence of Stage 2 or 3 liver fibrosis per the NASH CRN System based on central reading of the screening biopsy slides. Subjects newly randomized in Part 2 must have histological evidence of Stage 3 liver fibrosis per the NASH CRN System, based on central reading of the Screening period biopsy slides.
5. Females of childbearing potential and males participating in the study must agree to use at least 2 approved methods of contraception throughout the duration of the study and for 30 days after stopping study drug.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1800
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 200

Exclusion criteria:
1. Inability to undergo a liver biopsy safely
2. Hepatitis B surface antigen (HBsAg) positive
3. Hepatitis C antibody (HCVAb) positive
4. Human immunodeficiency virus (HIV)-1 or HIV-2 infection
5. Prior or planned liver transplantation
6. Other known causes of chronic liver disease
7. History or presence of cirrhosis (NASH CRN Fibrosis Stage 4) and/or hepatic decompensation including ascites, hepatic encephalopathy or variceal bleeding
8. Alcohol consumption greater than 21 units/week for males or 14 units/week for females
9. AST > 5x upper limit of normal (ULN) at Screening
10. ALT > 5 x ULN at Screening
11. HbA1c > 9% at Screening
12. Serum albumin < 3.5 g/dL
13. Estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73 m2 according to the Modification of Diet in Renal Disease (MDRD) equation at Screening
14. Platelet count < 100,000/mm3 at Screening
15. Total bilirubin > 1.3 mg/dL (subjects with hyperbilirubinemia associated with documented Gilbert’s syndrome may be eligible upon review by the medical monitor) at Screening
16. International normalized ratio (INR) > 1.3
17. Model of end stage liver disease (MELD) score > 12
18. Weight reduction, defined as = 7% of body weight, through bariatric surgery in the past 5 years or bariatric surgery, planned during the conduct of the study (including gastric banding and sleeve surgery)
19.Known history of hepatocellular carcinoma (HCC) at any time, history of malignancy within the past 5 years or ongoing malignancy other than basal cell carcinoma, or resected noninvasive cutaneous squamous cell carcinoma or treated stage II or lower colorectal or breast cancer in remission for = 2 years and with documented low risk of recurrence (including but not limited to Oncotype DX 12 gene recurrence score <30 for stage II or lower colon cancer; early-stage, estrogen-receptor-positive, HER2-negative breast cancers that have not spread to the lymph nodes; Oncotype DX 21 gene recurrence score <18 for earlystage invasive breast cancer; or Oncotype DX ductal carcinoma in situ [DCIS] 12 gene recurrence score <39 for noninvasive breast cancer)
20. Active, serious infections that require parenteral therapy (antibiotic or antifungal) therapy within 30 days prior to Screening Visit
21. Clinically significant cardiovascular or cerebrovascular disease within the past 3 months
22. Females who are pregnant or breastfeeding
23. Current or anticipated treatment with radiation therapy, cytotoxic chemotherapeutic agents and immune-modulating agents (such as interleukins and interferons)
24. Receiving a glucagon-like peptide 1 (GLP-1) receptor agonist, a dipeptidyl peptidase 4 (DPP-4) inhibitor, a sodium–glucose cotransporter 2 (SGLT2) and/or SGLT1 inhibitor, inhibitor, or a thiazolidinedione (TZD) for less than 6 months of stable therapy prior to the liver biopsy at Screening period. Subjects on a stable therapy with a GLP-1 receptor agonist, DPP-4 inhibitor, SGLT1 and/or SGLT2 inhibitor, or a TZD for at least 6 months prior to the Screening liver biopsy may be considered eligible. (Important Note: if a historical biopsy is to be used, subjects need to be on stable therapy for at least 6 months prior to the day historical liver biopsy) was performed).
25. Receiving ongoing therapy with any disallowed medication during the conduct of the study. Disallowed medication in use prior to enrollment will be required to be discontinued. For medications that are disallowed due to significant drug

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Liver fibrosis in Subjects with Nonalcoholic Steatohepatitis
MedDRA version: 22.0 Level: PT Classification code 10053219 Term: Non-alcoholic steatohepatitis System Organ Class: 10019805 - Hepatobiliary disorders

Intervention(s)

Product Name: Cenicriviroc Mesylate
Product Code: CVC
Pharmaceutical Form: Tablet
INN or Proposed INN: CENICRIVIROC MESYLATE
CAS Number: 497223-25-3
Current Sponsor code: CENICRIVIROC
Other descriptive name: TBR-652
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: Primary Objective (Part 1):
•Demonstrate the superiority of CVC compared to placebo on liver histology at Month 12 relative to the Screening biopsy, in adult subjects with a liver biopsy diagnosis of NASH and Stage 2 or 3 liver fibrosis (by NASH CRN system) as confirmed by an independent central pathologist
Primary Objective (Part 2):
•Demonstrate the superiority of CVC compared to placebo on the composite endpoint of histopathologic progression to cirrhosis, (defined by NASH CRN Fibrosis Stage 4) liver-related clinical outcomes, and all-cause mortality, as measured by the time to first occurrence of any of the listed adjudicated events (clinical outcomes composite endpoint) – (all subjects)

Primary end point(s): (Part 1): Proportion of subjects with improvement in fibrosis by 2 stages (NASH CRN system) AND no worsening of steatohepatitis (no worsening of lobular inflammation or hepatocellular ballooning grade).
(Part 2): Time to first occurrence of any of the following adjudicated events:
Death (all cause), Histopathologic progression to cirrhosis (defined by NASH CRN Fibrosis Stage 4), Hepatocellular carcinoma, Liver transplant, MELD score =15, Ascites (requiring intervention, ie, large volume paracentesis = 1L or initiation of a diuretic) , Hospitalization (as defined by a stay of = 24 hours) for onset of: variceal bleed, hepatic encephalopathy (defined by a West Haven Stage of =2), spontaneous bacterial peritonitis (confirmed by diagnostic paracentesis with positive ascitic fluid bacterial culture)

Timepoint(s) of evaluation of this end point: Part 1: Month 12
Part 2: Duration of study

Secondary Objective: Part 1:
Evaluate the effect of CVC compared to placebo on liver histology at Month 12 relative to the screening biopsy for the proportion of subjects with improvement in fibrosis of at least 2 stages (NASH CRN system) AND no worsening of steatohepatitis
Part 1 and 2:Evaluate the effect of CVC compared to placebo on liver histology relative to the Screening biopsy for the proportion of subjects with improvement in fibrosis by at least 1 stage (NASH CRN system), regardless of effect on steatohepatitis. (months 12 and 60, as applicable).
Part 1 and 2: (2)Evaluate the safety and tolerability of CVC for the treatment of liver fibrosis in adult subjects with NASH.
Part 2: (3)Evaluate the effect of CVC compared to placebo on liver histology relative to the Screening biopsy for the proportion of subjects with improvement in fibrosis by at least 1 stage (NASH CRN system), AND no worsening of steatohepatitis (no worsening of lobular inflammation or hepatocellular ballooning grade).

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Months 12 and 60

Secondary end point(s): Parts 1 and 2:
Proportion of subjects with improvement in fibrosis by at least 2 stages (NASH CRN system) AND no worsening of steatohepatitis (no worsening of lobular inflammation or hepatocellular ballooning grade) on liver histology at Month 12 relative to the screening biopsy.
Proportion of subjects with improvement in fibrosis by at least 1 stage (NASH CRN system), regardless of effect on steatohepatitis, relative to the Screening biopsy.
Proportion of subjects with improvement in fibrosis by at least 2 stages (NASH CRN system), regardless of effect on steatohepatitis, at Month 12 relative to the screening biopsy.
Part 2: Proportion of subjects with improvement in fibrosis by at least 1 stage (NASH CRN system) AND no worsening of steatohepatitis (no worsening of lobular inflammation or hepatocellular ballooning grade) on liver biopsy relative to the Screening biopsy

Secondary ID(s)

2016-004566-26-BE

3152-301-002

Source(s) of Monetary Support

Tobira Therapeutics, Inc., a subsidiary of Allergan plc,

Ethics review

Status: Approved
Approval date: 26/06/2017
Contact: