Rollover Study of Cenicriviroc for the Treatment of Liver Fibrosis in Participants With Nonalcoholic Steatohepatitis

• Sponsor: Tobira Therapeutics, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03059446
• Collaborator: (none)
• Enrollment: 167
• Locations: 71
• Arm: 1
• Actual Duration (Months): 46.7
• Patients Per Site: 2.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This rollover study will provide open-label treatment with cenicriviroc and will assess the long-term safety of continued treatment with cenicriviroc in participants who participated in either the CENTAUR study 652-2-203 [NCT02217475] or the AURORA study [NCT03028740].

Condition or Disease	Intervention/Treatment	Phase
Nonalcoholic Steatohepatitis; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease	Drug: Cenicriviroc	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 167 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-label Rollover Study of Cenicriviroc for the Treatment of Liver Fibrosis in Adult Subjects With Nonalcoholic Steatohepatitis (NASH)
• Actual Study Start Date: Feb 14, 2017
• Actual Primary Completion Date: Jan 5, 2021
• Actual Study Completion Date: Jan 5, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cenicriviroc (CVC) 150 mg Cenicriviroc 150 mg tablet once daily in the morning with food until the study was terminated (up to approximately 4 years).	Drug: Cenicriviroc; Cenicriviroc immediate release tablets; Other Names: CVC

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-emergent Adverse Events (AE) [Day 1 until the study was terminated (up to approximately 4 years)]

   An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with the treatment. A treatment-emergent AE is an AE that occurs after a participant receives study drug.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Successful completion of both Treatment Period 1 and Treatment Period 2, of the CENTAUR Study (652-2-203), including a Year 2 liver biopsy.

• Completed the AURORA study (3152-301-002) as a result of reaching an adjudicated liver-related clinical outcome in Part 1 or Part 2 of the study of:

• Histopathological progression to cirrhosis

• Model for end-stage liver disease (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).

Exclusion Criteria:

• Prior or planned liver transplantation

• Other know causes of chronic liver disease such as: Alcoholic liver disease, Primary biliary cirrhosis, Primary sclerosing cholangitis, Autoimmune hepatitis, Wilson's disease, hemochromatosis, or iron overload, or Alpha-1 antitrypsin (A1AT) deficiency.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Digestive Health Specialists of the Southeast - Dothan	Dothan	Alabama	United States	36305
2	Mayo Clinic Hospital	Phoenix	Arizona	United States	85054
3	Adobe Clinical Research, LLC	Tucson	Arizona	United States	85712
4	Franco Felizarta, MDv	Bakersfield	California	United States	93301
5	University of California, San Diego (UCSD)	La Jolla	California	United States	92037
6	Inland Empire Liver Foundation	Rialto	California	United States	92377
7	University of California, San Diego (UCSD) - Medical Center	San Diego	California	United States	92093
8	Quest Clinical Research	San Francisco	California	United States	94115
9	Upland Clinical Research	Upland	California	United States	91786
10	Island View Gastroenterology Associates	Ventura	California	United States	93003
11	University of Miami - Schiff Center for Liver Diseases	Miami	Florida	United States	33136
12	Advanced Medical Research	Port Orange	Florida	United States	32127
13	Florida Health Sciences Center, Inc. d/b/a Tampa General Hospital	Tampa	Florida	United States	33606
14	Rush University Medical Center	Chicago	Illinois	United States	60612
15	University of Iowa Hospital and Clinics	Iowa City	Iowa	United States	52242
16	Kansas Medical Clinic PA	Topeka	Kansas	United States	66606
17	Delta Research Partners, Llc	Bastrop	Louisiana	United States	71220
18	Tandem Clinical Research LLC	Marrero	Louisiana	United States	70072
19	Tulane University Medical Center	New Orleans	Louisiana	United States	70112
20	Mercy Medical Center - Baltimore, Maryland	Baltimore	Maryland	United States	21202
21	Johns Hopkins University School of Medicine	Baltimore	Maryland	United States	21287
22	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
23	Henry Ford Health System	Detroit	Michigan	United States	48202
24	Minnesota Gastroenterology, P.A.	Saint Paul	Minnesota	United States	55114
25	Digestive Health Specialists	Tupelo	Mississippi	United States	38801
26	University of Buffalo - Erie County Medical Center	Buffalo	New York	United States	14215
27	Carolinas Medical Center	Charlotte	North Carolina	United States	28204
28	Duke University Medical Center (DUMC)	Durham	North Carolina	United States	27710
29	Wake Research Associates, LLC - Raleigh	Raleigh	North Carolina	United States	27612
30	PMG Research of Winston-Salem, LLC	Winston-Salem	North Carolina	United States	27103
31	Consultants for Clinical Research - Cincinnati	Cincinnati	Ohio	United States	45249
32	Options Health Research, LLC	Tulsa	Oklahoma	United States	74104
33	ClinSearch LLC	Chattanooga	Tennessee	United States	37421
34	Gastro One	Germantown	Tennessee	United States	38138
35	Digestive Health Research	Lebanon	Tennessee	United States	37090
36	The University of Texas - Health Science Center & Medical School at Houston	Houston	Texas	United States	77030
37	The Texas Liver Institute	San Antonio	Texas	United States	78215
38	University of Utah	Salt Lake City	Utah	United States	84132
39	Virginia Commonwealth University Medical College of Virginia	Richmond	Virginia	United States	23249
40	Virginia Mason Medical Center	Seattle	Washington	United States	98101
41	Swedish Medical Center	Seattle	Washington	United States	98104
42	Royal Brisbane Hospital and Women's Hospital	Herston	Queensland	Australia	4029
43	Central Adelaide Local Health Network Inc - Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
44	Flinders Medical Centre	Bedford Park	South Australia	Australia	5042
45	Monash Medical Centre	Clayton	Victoria	Australia	3168
46	Austin Health	Heidelberg	Victoria	Australia	3084
47	UCL Saint Luc Bruxelles	Brussel		Belgium	1200
48	University Hospital Erasmus (Brussels)	Bruxelles		Belgium	1070
49	Antwerp University Hospital (UZA)	Edegem		Belgium	2650
50	CHU Angers	Angers Cedex 09		France	49933
51	Hopital Saint Antoine	Paris		France	75012
52	Purpan CHU Toulouse	Toulouse, cedex 9		France	31059
53	Uniklinik RWTH Aachen	Aachen		Germany	52074
54	Charite - University Hospital Berlin - Campus Virchow - Hospital	Berlin		Germany	13353
55	Universitaetsklinikum Hamburg-Eppendorf - I. Medizinische Klinik und Poliklinik	Hamburg		Germany	20246
56	Universitaetsklinikum Heidelberg - Innere Medizin IV	Heidelberg		Germany	69120
57	Uniklinik Koeln, Poliklinik fuer Endokrinologie, Diabetologie und Praeventivmedizin (ZEDP)	Koeln		Germany	50937
58	Eugastro GmbH	Leipzig		Germany	4103
59	University Hospital Giessen and Marburg GmbH	Marburg		Germany	35043
60	Prince of Wales Hospital	Shatin		Hong Kong	Hong Kong
61	Policlinico S. Orsola-Malpighi	Bologna		Italy	40138
62	Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico di Milano	Milano		Italy	20122
63	AOU Policlinico Paolo Giaccone di Palermo	Palermo		Italy	90127
64	ID Clinic	Myslowice		Poland	41-400
65	Centrum Badan Klinicznych Piotr Napora Lekarze Sp. p.	Wroclaw		Poland	50-349
66	Fundacion de Investigacion de Diego	San Juan		Puerto Rico	927
67	Hospital Universitario Vall d'Hebron	Barcelona		Spain	8022
68	Hospital de la Santa Creu i Sant Pau Barcelona	Barcelona		Spain	8026
69	Hospital General Universitario Gregorio Maranon	Madrid		Spain	28007
70	Nottingham NHS Treatment Centre	Nottingham		United Kingdom	NG7 2UH
71	Queen Alexandra Hospital	Portsmouth		United Kingdom	PO6 3LY

Sponsors and Collaborators

• Tobira Therapeutics, Inc.

Investigators

• Study Director: Eduardo B Martins, Allergan

Study Documents (Full-Text)

• Study Protocol - Apr 14, 2018
• Statistical Analysis Plan - Jan 30, 2019

More Information

Publications

None provided.

• Responsible Party: Tobira Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT03059446
• Other Study ID Numbers: 3152-201-002; 2016-004754-15
• First Posted: Feb 23, 2017
• Last Update Posted: Feb 2, 2022
• Last Verified: Sep 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Liver Diseases; Fatty Liver; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Cenicriviroc

Study Results

Participant Flow

Pre-assignment Detail	Participants who completed the CENTAUR study [NCT02217475] or the AURORA study [NCT03028740] were eligible for enrollment in this rollover study.

Arm/Group Title	Cenicriviroc (CVC) 150 mg
Arm/Group Description	Cenicriviroc 150 mg tablet once daily in the morning with food until the study was terminated (up to approximately 4 years).
Period Title: Overall Study
STARTED	167
COMPLETED	0
NOT COMPLETED	167

Baseline Characteristics

Arm/Group Title	Cenicriviroc (CVC) 150 mg
Arm/Group Description	Cenicriviroc 150 mg tablet once daily in the morning with food until the study was terminated (up to approximately 4 years).
Overall Participants	167
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.8 (10.41)
Sex: Female, Male (Count of Participants)
Female	88 52.7%
Male	79 47.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	24 14.4%
Not Hispanic or Latino	143 85.6%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.6%
Asian	9 5.4%
Native Hawaiian or Other Pacific Islander	2 1.2%
Black or African American	4 2.4%
White	150 89.8%
More than one race	0 0%
Unknown or Not Reported	1 0.6%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (AE)
Description	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with the treatment. A treatment-emergent AE is an AE that occurs after a participant receives study drug.
Time Frame	Day 1 until the study was terminated (up to approximately 4 years)

Outcome Measure Data

Analysis Population Description

Safety Population included all participants who received at least one dose of study drug.

Arm/Group Title	Cenicriviroc (CVC) 150 mg
Arm/Group Description	Cenicriviroc 150 mg tablet once daily in the morning with food until the study was terminated (up to approximately 4 years).
Measure Participants	167
Count of Participants [Participants]	140 83.8%

Adverse Events

Time Frame	Day 1 until the study was terminated (Up to approximately 4 years)
Arm/Group Title	Cenicriviroc (CVC) 150 mg
Arm/Group Description	Cenicriviroc 150 mg tablet once daily in the morning with food until the study was terminated (up to approximately 4 years).
All Cause Mortality
	Cenicriviroc (CVC) 150 mg
	Affected / at Risk (%)	# Events
Total	1/167 (0.6%)
Serious Adverse Events
	Cenicriviroc (CVC) 150 mg
	Affected / at Risk (%)	# Events
Total	40/167 (24%)
Cardiac disorders
Angina pectoris	3/167 (1.8%)
Acute coronary syndrome	1/167 (0.6%)
Angina unstable	1/167 (0.6%)
Atrial fibrillation	1/167 (0.6%)
Coronary artery occlusion	1/167 (0.6%)
Tachycardia	1/167 (0.6%)
Ear and labyrinth disorders
Vertigo	1/167 (0.6%)
Eye disorders
Retinal artery occlusion	1/167 (0.6%)
Gastrointestinal disorders
Abdominal pain upper	1/167 (0.6%)
Food poisoning	1/167 (0.6%)
Pancreatitis	1/167 (0.6%)
Salivary gland calculus	1/167 (0.6%)
Vomiting	1/167 (0.6%)
General disorders
Asthenia	1/167 (0.6%)
Hepatobiliary disorders
Cholecystitis acute	2/167 (1.2%)
Cholecystitis	1/167 (0.6%)
Infections and infestations
Cellulitis	3/167 (1.8%)
Pneumonia legionella	2/167 (1.2%)
Sepsis	2/167 (1.2%)
Bone abscess	1/167 (0.6%)
COVID-19 pneumonia	1/167 (0.6%)
Carbuncle	1/167 (0.6%)
Empyema	1/167 (0.6%)
Gastroenteritis	1/167 (0.6%)
Liver abscess	1/167 (0.6%)
Pneumonia	1/167 (0.6%)
Q fever	1/167 (0.6%)
Injury, poisoning and procedural complications
Contusion	1/167 (0.6%)
Post procedural fever	1/167 (0.6%)
Post procedural haemorrhage	1/167 (0.6%)
Road traffic accident	1/167 (0.6%)
Spinal compression fracture	1/167 (0.6%)
Toxicity to various agents	1/167 (0.6%)
Investigations
Weight decreased	1/167 (0.6%)
Metabolism and nutrition disorders
Dehydration	3/167 (1.8%)
Gout	1/167 (0.6%)
Hypoglycaemia	1/167 (0.6%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	1/167 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	2/167 (1.2%)
Bowen's disease	2/167 (1.2%)
Hepatocellular carcinoma	1/167 (0.6%)
Invasive lobular breast carcinoma	1/167 (0.6%)
Ovarian cancer	1/88 (1.1%)
Papillary thyroid cancer	1/167 (0.6%)
Renal cancer	1/167 (0.6%)
Renal cell carcinoma	1/167 (0.6%)
Squamous cell carcinoma of skin	1/167 (0.6%)
Nervous system disorders
Cerebrovascular accident	1/167 (0.6%)
Dizziness	1/167 (0.6%)
Headache	1/167 (0.6%)
Migraine with aura	1/167 (0.6%)
Syncope	1/167 (0.6%)
Uraemic encephalopathy	1/167 (0.6%)
Vertebral artery stenosis	1/167 (0.6%)
Renal and urinary disorders
Acute kidney injury	3/167 (1.8%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/167 (0.6%)
Vascular disorders
Hypertension	1/167 (0.6%)
Lymphatic fistula	1/167 (0.6%)
Other (Not Including Serious) Adverse Events
	Cenicriviroc (CVC) 150 mg
	Affected / at Risk (%)	# Events
Total	98/167 (58.7%)
Gastrointestinal disorders
Diarrhoea	20/167 (12%)
Nausea	13/167 (7.8%)
Abdominal pain	12/167 (7.2%)
Abdominal pain upper	12/167 (7.2%)
Constipation	12/167 (7.2%)
General disorders
Fatigue	10/167 (6%)
Infections and infestations
Nasopharyngitis	17/167 (10.2%)
Influenza	14/167 (8.4%)
Bronchitis	12/167 (7.2%)
Sinusitis	9/167 (5.4%)
Upper respiratory tract infection	9/167 (5.4%)
Investigations
Alanine aminotransferase increased	10/167 (6%)
Metabolism and nutrition disorders
Diabetes mellitus	12/167 (7.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	22/167 (13.2%)
Respiratory, thoracic and mediastinal disorders
Cough	9/167 (5.4%)
Skin and subcutaneous tissue disorders
Rash	13/167 (7.8%)

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.