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

• Register: EUCTR
• Last refreshed on: 12 April 2021
• Main ID: EUCTR2016-004566-26-HU
• Date of registration: 20/04/2017
• 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: 15/06/2017
• 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: Kathleen Waldron (Reg. Affairs)
• Affiliation: Tobira Therapeutics, Inc., a subsidiary of Allergan plc

• Name: Kathleen Waldron (Reg. Affairs)
• 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 biopsy slides
4. Histological evidence of Stage 2 to 3 liver fibrosis per the NASH CRN System based on central reading of the 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
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 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 > 8 x upper limit of normal (ULN) at Screening
10. ALT > 8 x ULN at Screening
11. HbA1c > 10% 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
14. Platelet count < 100,000/mm3
15. Total bilirubin > 1.5 mg/dL (subjects with hyperbilirubinemia associated with documented Gilbert’s syndrome may be eligible upon review by the medical monitor)
16. International normalized ratio (INR) > 1.3
17. Model of end stage liver disease (MELD) score > 12
18. Weight reduction through bariatric surgery in the past 5 years or 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 low risk of recurrence (ie, Oncotype DX 12 gene recurrence score <30 for stage II or lower colon cancer; early-stage, estrogen-receptor-positive, HER2-negative breast cancers that haven’t spread to the lymph nodes; Oncotype DX 21 gene recurrence score <18 for early-stage 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 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 immunomodulating agents (such as systemic corticosteroids, interleukins, 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) inhibitor, or a thiazolidinedione (TZD) for less than 6 months of stable therapy prior to the liver biopsy at Screening
25. Receiving ongoing therapy with any disallowed medication between Screening and Baseline visits.
26. Allergy to the study drug or its components
27. Receiving any investigational products within 30 days prior to Screening or anticipated use during the trial
28. Receiving any investigational product being evaluated for the treatment of liver fibrosis or NASH in the 6 months prior to the Screening liver biopsy (subjects documented to be assigned to placebo in such trials may be eligible immediately following completion of their participation in the previous trial)
29. Participation in any other clinical trial at Screening without approval from the sponsor
30. Any other clinically significant disorders or prior therapy that, in the opinion of the investigator, would make the sub

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

Health Condition(s) or Problem(s) studied

Liver fibrosis in Subjects with Nonalcoholic Steatohepatitis
MedDRA version: 20.1 Level: PT Classification code 10053219 Term: Non-alcoholic steatohepatitis System Organ Class: 10019805 - Hepatobiliary disorders

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

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, by assessing 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)
Primary Objective (Part 2):
•Demonstrate the superiority of CVC compared to placebo on the composite endpoint of histopathologic progression to cirrhosis, 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)

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

Primary end point(s): (Part 1): 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 histology relative to the Screening biopsy
(Part 2): Time to first occurrence of any of the following adjudicated events:
Death (all cause), Histopathologic progression to cirrhosis, Hepatocellular carcinoma, Liver transplant, MELD score =15, Ascites (requiring intervention, ie, large volume paracentesis = 1L or initiation of 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)

Secondary Objective: Part 1 and 2: (1)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), (months 12 and 60, as applicable)).

Secondary Outcome(s)

Secondary end point(s): Parts 1 and 2: 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
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

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

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: 29/05/2017
Contact: