AURORA: A Study for the Efficacy and Safety of Cenicriviroc (CVC) for the Treatment of Liver Fibrosis in Adults With Nonalcoholic Steatohepatitis (NASH)
Sponsor
Tobira Therapeutics, Inc. (Industry)
Overall Status
Terminated
CT.gov ID
NCT03028740
Collaborator
(none)
1,778
346
2
47.1
5.1
0.1
Study Details
Study Description
Brief Summary
The AURORA study will be conducted to confirm the efficacy and safety of cenicriviroc (CVC) for the treatment of liver fibrosis in adult participants with NASH.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
The AURORA study will be conducted in 2 parts. Part 1 will examine the surrogate endpoint of improvement in fibrosis of at least 1 stage (nonalcoholic steatohepatitis clinical research network [NASH CRN]) and no worsening of steatohepatitis at Month 12. Participants from Part 1 will continue into Part 2 and additional participants will be newly randomized in Part 2 to determine long-term clinical outcomes composed of histopathologic progression to cirrhosis, liver-related clinical outcomes, and all-cause mortality.
Study Design
Study Type:
Interventional
Actual Enrollment
:
1778 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
AURORA: 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
Actual Study Start Date
:
Apr 5, 2017
Actual Primary Completion Date
:
Jan 12, 2021
Actual Study Completion Date
:
Mar 9, 2021
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months. |
Drug: Placebo
Cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months.
|
| Experimental: Cenicriviroc 150 mg Participants received cenicriviroc, 150 milligrams (mg), tablet, orally, once daily for up to approximately 40 months. |
Drug: Cenicriviroc
Cenicriviroc, 150 mg, tablet, orally, once daily for up to approximately 40 months.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Part 1: Percentage of Participants With Improvement in Fibrosis by at Least 1 Stage and No Worsening of Steatohepatitis on Liver Histology at Month 12 [Month 12]
Fibrosis stage was evaluated using the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Staging System with stages: 0=none; 1=perisinusoidal or periportal; 1A=mild, zone 3, perisinusoidal; 1B=moderate, zone 3, perisinusoidal; 1C=portal/periportal; 2=perisinusoidal and portal/periportal; 3=bridging fibrosis; 4=cirrhosis. No worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade as per scoring in relevant nonalcoholic fatty liver disease activity score (NAS) categories. NAS is a semiquantitative scoring system based on the unweighted sum of: steatosis (0=<5% to 3=>66%), lobular inflammation (0=no foci to 3=>4 foci/200x), and hepatocellular ballooning (0=none to 2=many cells/prominent ballooning) scores. Improvement in fibrosis is a decrease in the NASH CRN fibrosis stage.
- Time to First Occurrence of Adjudicated Events in the Full Study Cohort [From first dose of study drug to onset of first occurrence of the event (Up to approximately 42 months)]
Time to first occurrence from Baseline was defined as the number of days from the first dose of randomized investigational product to the onset of the first occurrence of any of the following adjudicated events: death (all cause), histopathologic progression to cirrhosis, liver transplant, model for end stage liver disease (MELD) score ≥15, ascites, hospitalization for onset of: variceal bleed, hepatic encephalopathy, spontaneous bacterial peritonitis. MELD is a scoring system for assessing the severity of chronic liver disease and uses the participant's values for total bilirubin, serum creatinine, and the international normalized ratio for prothrombin time to predict survival. MELD score ranges from 6 (less ill) to 40 (gravely ill) with scores and mortality probability being: Score 40=71.3% mortality; Scores 30-39=52.6% mortality; Scores 20-29=19.6% mortality; Scores10-19=6.0% mortality; Score 9 or less=1.9% mortality.
Secondary Outcome Measures
- Part 1: Percentage of Participants With Improvement in Fibrosis by at Least 2 Stages and No Worsening of Steatohepatitis on Liver Histology at Month 12 [Month 12]
Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages: 0=none; 1=perisinusoidal or periportal; 1A=mild, zone 3, perisinusoidal; 1B=moderate, zone 3, perisinusoidal; 1C=portal/periportal; 2=perisinusoidal and portal/periportal; 3=bridging fibrosis; 4=cirrhosis. No worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade as per scoring in relevant NAS categories. NAS is a semiquantitative scoring system based on the unweighted sum of: steatosis (0=<5% to 3=>66%), lobular inflammation (0=no foci to 3=>4 foci/200x), and hepatocellular ballooning (0=none to 2=many cells/prominent ballooning) scores. Improvement in fibrosis is a decrease in the NASH CRN fibrosis stage.
- Part 1: Percentage of Participants With Improvement in Fibrosis by at Least 1 Stage Regardless of Effect on Steatohepatitis at Month 12 [Month 12]
Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages 0=none, 1=perisinusoidal or periportal, 1A=mild, zone 3, perisinusoidal, 1B=moderate, zone 3, perisinusoidal, 1C=portal/periportal, 2=perisinusoidal and portal/periportal, 3=bridging fibrosis, 4=cirrhosis.
- Part 1: Percentage of Participants With Improvement in Fibrosis by at Least 2 Stages Regardless of Effect on Steatohepatitis at Month 12 [Month 12]
Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages 0=none, 1=perisinusoidal or periportal, 1A=mild, zone 3, perisinusoidal, 1B=moderate, zone 3, perisinusoidal, 1C=portal/periportal, 2=perisinusoidal and portal/periportal, 3=bridging fibrosis, 4=cirrhosis.
- Percentage of Participants With Improvement in Fibrosis by at Least 1 Stage and No Worsening of Steatohepatitis on Liver Biopsy at Month 12 in the Full Study Cohort [Month 12]
Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages: 0=none; 1=perisinusoidal or periportal; 1A=mild, zone 3, perisinusoidal; 1B=moderate, zone 3, perisinusoidal; 1C=portal/periportal; 2=perisinusoidal and portal/periportal; 3=bridging fibrosis; 4=cirrhosis. No worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade as per scoring in relevant NAS categories. NAS is a semiquantitative scoring system based on the unweighted sum of: steatosis (0=<5% to 3=>66%), lobular inflammation (0=no foci to 3=>4 foci/200x), and hepatocellular ballooning (0=none to 2=many cells/prominent ballooning) scores. Improvement in fibrosis is a decrease in the NASH CRN fibrosis stage.
- Percentage of Participants With Improvement in Fibrosis by at Least 1 Stage Regardless of Effect on Steatohepatitis on Liver Biopsy at Month 12 in the Full Study Cohort [Month 12]
Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages 0=none, 1=perisinusoidal or periportal, 1A=mild, zone 3, perisinusoidal, 1B=moderate, zone 3, perisinusoidal, 1C=portal/periportal, 2=perisinusoidal and portal/periportal, 3=bridging fibrosis, 4=cirrhosis.
- Percentage of Participants With Improvement in Fibrosis by at Least 2 Stages and No Worsening of Steatohepatitis on Liver Biopsy at Month 12 in the Full Study Cohort [Month 12]
Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages: 0=none; 1=perisinusoidal or periportal; 1A=mild, zone 3, perisinusoidal; 1B=moderate, zone 3, perisinusoidal; 1C=portal/periportal; 2=perisinusoidal and portal/periportal; 3=bridging fibrosis; 4=cirrhosis. No worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade as per scoring in relevant NAS categories. NAS is a semiquantitative scoring system based on the unweighted sum of: steatosis (0=<5% to 3=>66%), lobular inflammation (0=no foci to 3=>4 foci/200x), and hepatocellular ballooning (0=none to 2=many cells/prominent ballooning) scores. Improvement in fibrosis is a decrease in the NASH CRN fibrosis stage.
- Percentage of Participants With Improvement in Fibrosis by at Least 2 Stages Regardless of Effect on Steatohepatitis on Liver Biopsy at Month 12 in the Full Study Cohort [Month 12]
Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages 0=none, 1=perisinusoidal or periportal, 1A=mild, zone 3, perisinusoidal, 1B=moderate, zone 3, perisinusoidal, 1C=portal/periportal, 2=perisinusoidal and portal/periportal, 3=bridging fibrosis, 4=cirrhosis.
- Percentage of Participants With Improvement in Fibrosis by at Least 1 Stage and No Worsening of Steatohepatitis on Liver Biopsy at Month 60 in the Full Study Cohort [Month 60]
Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages: 0=none; 1=perisinusoidal or periportal; 1A=mild, zone 3, perisinusoidal; 1B=moderate, zone 3, perisinusoidal; 1C=portal/periportal; 2=perisinusoidal and portal/periportal; 3=bridging fibrosis; 4=cirrhosis. No worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade as per scoring in relevant NAS categories. NAS is a semiquantitative scoring system based on the unweighted sum of: steatosis (0=<5% to 3=>66%), lobular inflammation (0=no foci to 3=>4 foci/200x), and hepatocellular ballooning (0=none to 2=many cells/prominent ballooning) scores. Improvement in fibrosis is a decrease in the NASH CRN fibrosis stage.
- Percentage of Participants With Improvement in Fibrosis by at Least 1 Stage Regardless of Effect on Steatohepatitis on Liver Biopsy at Month 60 in the Full Study Cohort [Month 60]
Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages 0=none, 1=perisinusoidal or periportal, 1A=mild, zone 3, perisinusoidal, 1B=moderate, zone 3, perisinusoidal, 1C=portal/periportal, 2=perisinusoidal and portal/periportal, 3=bridging fibrosis, 4=cirrhosis.
- Percentage of Participants With Improvement in Fibrosis by at Least 2 Stages and No Worsening of Steatohepatitis on Liver Biopsy at Month 60 in the Full Study Cohort [Month 60]
Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages: 0=none; 1=perisinusoidal or periportal; 1A=mild, zone 3, perisinusoidal; 1B=moderate, zone 3, perisinusoidal; 1C=portal/periportal; 2=perisinusoidal and portal/periportal; 3=bridging fibrosis; 4=cirrhosis. No worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade as per scoring in relevant NAS categories. NAS is a semiquantitative scoring system based on the unweighted sum of: steatosis (0=<5% to 3=>66%), lobular inflammation (0=no foci to 3=>4 foci/200x), and hepatocellular ballooning (0=none to 2=many cells/prominent ballooning) scores. Improvement in fibrosis is a decrease in the NASH CRN fibrosis stage.
- Percentage of Participants With Improvement in Fibrosis by at Least 2 Stages Regardless of Effect on Steatohepatitis on Liver Biopsy at Month 60 in the Full Study Cohort [Month 60]
Fibrosis stage was evaluated using NASH CRN Fibrosis Staging System with stages 0=None, 1=Perisinusoidal or periportal, 1A=Mild, zone 3, perisinusoidal, 1B=Moderate, zone 3, perisinusoidal, 1C=Portal/periportal, 2=Perisinusoidal and portal/periportal, 3=Bridging fibrosis, 4=Cirrhosis.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Male and female participants aged between 18-75 years
-
Ability to understand and sign a written informed consent form (ICF)
-
Histological evidence of NASH based on central reading of the Screening biopsy
-
Participants included in Part 1 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. Participants 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. Historical biopsy can be used, provided the criteria listed on Item 3a above are fulfilled.
-
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. Females who are postmenopausal must have documentation of cessation of menses for ≥12 months and serum follicle-stimulating hormone (FSH) ≥30 milliunits (mU)/milliliter (mL) at Screening.
Exclusion Criteria:
-
Inability to undergo a liver biopsy
-
Hepatitis B surface antigen (HBsAg) positive
-
Hepatitis C antibody (HCVAb) positive
-
Human immunodeficiency virus (HIV)-1 or HIV-2 infection
-
Prior or planned liver transplantation
-
Other known causes of chronic liver disease
-
History or presence 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
-
Aspartate transaminase (AST) >200 International units (IU)/liter (L) in males and females at Screening
-
Alanine transaminase (ALT) >250 IU/L in males and >200 IU/L in females at Screening
-
Hemoglobin A1c (HbA1c) >10% at Screening
-
Serum albumin <3.5 gram (g)/deciliter (dL) at Screening
-
Estimated glomerular filtration rate (eGFR) < 50 mL/minute (min)/1.73 meter (m)^2 according to the Modification of Diet in Renal Disease (MDRD) equation
-
Platelet count <100,000/millimeter (mm)^3
-
Total bilirubin >1.5 milligram (mg)/dL
-
International normalized ratio (INR) >1.3
-
Model of end stage liver disease (MELD) score >12
-
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)
-
History of malignancy within the past 5 years or ongoing malignancy other than basal cell carcinoma, or resected noninvasive cutaneous squamous cell carcinoma
-
Active, serious infections that require parenteral antibiotic or antifungal therapy within 30 days prior to Screening Visit
-
Clinically significant cardiovascular or cerebrovascular disease within the past 3 months
-
Females who are pregnant or breastfeeding
-
Current or anticipated treatment with radiation therapy, cytotoxic chemotherapeutic agents and immunomodulating agents (eg, interleukins, interferons, cyclosporine, tacrolimus) except for vaccines or short-term corticosteroids
-
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 sodium-glucose cotransporter (SGLT1) inhibitor, or a thiazolidinedione (TZD) for less than 6 months prior to the Screening period liver biopsy. Participants 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, participants need to be on stable therapy for at least 6 months prior to the day historical liver biopsy was performed).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Summit Internal Medicine | Birmingham | Alabama | United States | 35243 |
| 2 | Cullman Clinical Trials | Cullman | Alabama | United States | 35055 |
| 3 | Digestive Health Specialists of the Southeast | Dothan | Alabama | United States | 36305 |
| 4 | Objective GI D/B/A North Alabama GI Research Center | Madison | Alabama | United States | 35758 |
| 5 | The Institute for Liver Health | Chandler | Arizona | United States | 85224 |
| 6 | Adobe Gastroenterology Research, LLC | Tucson | Arizona | United States | 85712 |
| 7 | Del Sol Research Management, LLC | Tucson | Arizona | United States | 85712 |
| 8 | Del Sol Research Management LLC | Tucson | Arizona | United States | 85745 |
| 9 | Arkansas Diagnostic Center | Little Rock | Arkansas | United States | 72205 |
| 10 | Franco Felizarta MD | Bakersfield | California | United States | 93301 |
| 11 | Hope Clinical Research | Canoga Park | California | United States | 91303 |
| 12 | GW Research | Chula Vista | California | United States | 91910 |
| 13 | eStudySite | Chula Vista | California | United States | 91911 |
| 14 | Southern California Research Center | Coronado | California | United States | 92118 |
| 15 | Citrus Valley Gastroenterology | Covina | California | United States | 91722 |
| 16 | TriWest Research Associates | El Cajon | California | United States | 92020 |
| 17 | University of San Francisco, Fresno Medical Education Program | Fresno | California | United States | 93701 |
| 18 | Fresno Clinical Research Center (FCRC) | Fresno | California | United States | 93720 |
| 19 | National Research Institute | Huntington Park | California | United States | 90255 |
| 20 | University of California San Diego | La Jolla | California | United States | 92037 |
| 21 | eStudySite | La Mesa | California | United States | 91942 |
| 22 | Om Research | Lancaster | California | United States | 93534 |
| 23 | Southern California Kaiser Permanente, Los Angeles Medical Center | Los Angeles | California | United States | 90027 |
| 24 | GastroIntestinal Biosciences | Los Angeles | California | United States | 90036 |
| 25 | Global Research Institute | Los Angeles | California | United States | 90036 |
| 26 | Ruane Medical and Liver Health Institute | Los Angeles | California | United States | 90036 |
| 27 | Cedars-Sinai Medical Group | Los Angeles | California | United States | 90048 |
| 28 | National Research Institute | Los Angeles | California | United States | 90057 |
| 29 | United Medical Doctors | Murrieta | California | United States | 92563 |
| 30 | Palmtree Clinical Research Inc. | Palm Springs | California | United States | 92262 |
| 31 | National Research Institute | Panorama City | California | United States | 91402 |
| 32 | Pasadena Liver Center | Pasadena | California | United States | 91105 |
| 33 | Alliance Clinical Research LLC | Poway | California | United States | 92064 |
| 34 | Stanford School of Medicine, Center for Clinical Sciences Research | Redwood City | California | United States | 94063 |
| 35 | Inland Empire Liver Foundation | Rialto | California | United States | 92377-4697 |
| 36 | Precision Research Institute | San Diego | California | United States | 92114 |
| 37 | Southern California Permanente Medical Group | San Diego | California | United States | 92154 |
| 38 | UCSF School of Medicine | San Francisco | California | United States | 94143-0538 |
| 39 | Upland Clinical Research | Upland | California | United States | 91786 |
| 40 | Island View GI | Ventura | California | United States | 93003 |
| 41 | Peak Gastroenterology Associates | Colorado Springs | Colorado | United States | 80907 |
| 42 | South Denver Gastroenterology, PC | Englewood | Colorado | United States | 80113 |
| 43 | Western States Clinical Research, Inc. | Wheat Ridge | Colorado | United States | 80033 |
| 44 | Gastroenterology Associates of Fairfield County | Bridgeport | Connecticut | United States | 06606 |
| 45 | Yale University - New Haven | New Haven | Connecticut | United States | 06511 |
| 46 | Innovative Medical Research of South Florida, Inc. | Aventura | Florida | United States | 33180 |
| 47 | Gastro Florida | Clearwater | Florida | United States | 33761 |
| 48 | Hi Tech and Global Research, LLC | Coral Gables | Florida | United States | 33134 |
| 49 | Top Medical Research, Inc | Cutler Bay | Florida | United States | 33189 |
| 50 | ICR Sites | Doral | Florida | United States | 33166 |
| 51 | Qway Research, LLC | Hialeah | Florida | United States | 33010 |
| 52 | Gastroenterology Associates - Crystal River | Inverness | Florida | United States | 34452 |
| 53 | Mayo Clinic College of Medicine | Jacksonville | Florida | United States | 32224 |
| 54 | Meridien Research | Lakeland | Florida | United States | 33803 |
| 55 | Florida Digestive Health Specialists | Lakewood Ranch | Florida | United States | 34211 |
| 56 | Meridien Research | Maitland | Florida | United States | 32751 |
| 57 | San Marcus Research Clinic | Miami Lakes | Florida | United States | 33014 |
| 58 | Clinical Pharmacology of Miami, LLC | Miami | Florida | United States | 33014 |
| 59 | Bruce W. Carter Department of Veterans Affairs Medical Center | Miami | Florida | United States | 33125 |
| 60 | Optimus U Corporation | Miami | Florida | United States | 33125 |
| 61 | University of Miami Hospital | Miami | Florida | United States | 33136 |
| 62 | Sanchez Clinical Research, Inc | Miami | Florida | United States | 33157 |
| 63 | Genoma Research Group Inc. | Miami | Florida | United States | 33165 |
| 64 | Medical Professional Clinical Research Center, INC | Miami | Florida | United States | 33165 |
| 65 | ProLive Medical Research | Miami | Florida | United States | 33175 |
| 66 | Advanced Research Institute, Inc. | New Port Richey | Florida | United States | 34653 |
| 67 | Bioclinical Research Alliance | Orlando | Florida | United States | 32806 |
| 68 | Omega Research Maitland, LLC | Orlando | Florida | United States | 32810 |
| 69 | IMIC, Inc | Palmetto Bay | Florida | United States | 33157 |
| 70 | Innovation Medical Research Center | Palmetto Bay | Florida | United States | 33157 |
| 71 | Gastroenterology Associates of Pensacola | Pensacola | Florida | United States | 32503 |
| 72 | Advanced Medical Research | Port Orange | Florida | United States | 32127 |
| 73 | Tampa General Hospital | Tampa | Florida | United States | 33606 |
| 74 | Guardian Angel Research Center | Tampa | Florida | United States | 33614 |
| 75 | Bioclinica Research | The Villages | Florida | United States | 32162 |
| 76 | Florida Medical Clinic | Zephyrhills | Florida | United States | 33542 |
| 77 | Summit Clinical Research, LLC | Athens | Georgia | United States | 30607 |
| 78 | Digestive Healthcare of Georgia - Atlanta | Atlanta | Georgia | United States | 30309 |
| 79 | Piedmont Healthcare INC. | Atlanta | Georgia | United States | 30309 |
| 80 | Gastroenterology Associates of Central Georgia | Macon | Georgia | United States | 31201 |
| 81 | GI Specialists of Georgia - Marietta Office | Marietta | Georgia | United States | 30060 |
| 82 | Northwestern University | Chicago | Illinois | United States | 60611 |
| 83 | Rush University Medical Center | Chicago | Illinois | United States | 60612 |
| 84 | Investigators Research Group, LLC | Brownsburg | Indiana | United States | 46112 |
| 85 | Indianapolis Gastroenterology Research Foundation | Indianapolis | Indiana | United States | 46237 |
| 86 | Aquiant Research | New Albany | Indiana | United States | 47150 |
| 87 | Digestive Research Alliance of Michiana | South Bend | Indiana | United States | 46635 |
| 88 | Iowa Digestive Disease Center | Clive | Iowa | United States | 50325 |
| 89 | University of Iowa Hospitals and Clinics | Iowa City | Iowa | United States | 52242 |
| 90 | University of Kansas Medical Center | Kansas City | Kansas | United States | 66160 |
| 91 | Kansas Medical Clinic-Gastroenterology | Topeka | Kansas | United States | 66606 |
| 92 | Delta Research Partners, LLC | Bastrop | Louisiana | United States | 71220 |
| 93 | Avant Research Associates LLC | Crowley | Louisiana | United States | 70526 |
| 94 | C-1 Headlands, Inc. | Lake Charles | Louisiana | United States | 70601 |
| 95 | Tandem Clinical Research | Marrero | Louisiana | United States | 70072 |
| 96 | Tulane University School of Medicine | New Orleans | Louisiana | United States | 70112 |
| 97 | Ochsner Medical Center | New Orleans | Louisiana | United States | 70121 |
| 98 | Nola Research Works, LLC | New Orleans | Louisiana | United States | 70125 |
| 99 | Louisiana Research Center | Shreveport | Louisiana | United States | 71105 |
| 100 | Clinical Trials of America LLC | West Monroe | Louisiana | United States | 71291 |
| 101 | Mercy Medical Center | Baltimore | Maryland | United States | 21202 |
| 102 | Digestive Disease Associates | Catonsville | Maryland | United States | 21228 |
| 103 | Gastro Center of Maryland | Columbia | Maryland | United States | 21045 |
| 104 | Woodholme Gastroenterology Associates | Glen Burnie | Maryland | United States | 21061 |
| 105 | Victory Clinical Research | Greenbelt | Maryland | United States | 20770 |
| 106 | Meritus Center for Clinical Research | Hagerstown | Maryland | United States | 21742 |
| 107 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
| 108 | Beth Israel Deaconess Medical Center | Boston | Massachusetts | United States | 02215 |
| 109 | Lahey Hospital & Medical Center | Burlington | Massachusetts | United States | 01805 |
| 110 | Umass Memorial Medical Center | Worcester | Massachusetts | United States | 01655 |
| 111 | Henry Ford Health System | Detroit | Michigan | United States | 48202 |
| 112 | Minnesota Gastroenterology, P.A. | Maplewood | Minnesota | United States | 55117 |
| 113 | National Diabetes and Obesity Research Institute | Biloxi | Mississippi | United States | 39532 |
| 114 | GastroIntestinal Associates | Flowood | Mississippi | United States | 39232 |
| 115 | Clinical Research Professionals | Chesterfield | Missouri | United States | 63005 |
| 116 | Saint Louis University | Saint Louis | Missouri | United States | 63104 |
| 117 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
| 118 | Machuca Family Medicine | Las Vegas | Nevada | United States | 89104 |
| 119 | Jubilee Clinical Research, Inc. | Las Vegas | Nevada | United States | 89106 |
| 120 | Sierra Clinical Research | Las Vegas | Nevada | United States | 89106 |
| 121 | Excel Clinical Research | Las Vegas | Nevada | United States | 89109 |
| 122 | Dartmouth Hitchcock Medical Center | Lebanon | New Hampshire | United States | 03756 |
| 123 | Hassman Research Institute | Berlin | New Jersey | United States | 08009 |
| 124 | Amici Clinical Research | Raritan | New Jersey | United States | 08869 |
| 125 | Beth Israel Medical Center | New York | New York | United States | 10003 |
| 126 | NYU Langone Health - Perlmutter Cancer Center | New York | New York | United States | 10016 |
| 127 | Mount Sinai Medical Center | New York | New York | United States | 10029 |
| 128 | Tandem Clinical Research | New York | New York | United States | 10033 |
| 129 | Weill Cornell Medical College | New York | New York | United States | 10065 |
| 130 | Investigational Drug Service, The University of North Carolina at Chapel Hill | Chapel Hill | North Carolina | United States | 27514 |
| 131 | Carolinas Medical Center | Charlotte | North Carolina | United States | 28204 |
| 132 | Northeast GI Research Division | Concord | North Carolina | United States | 28027 |
| 133 | Duke University | Durham | North Carolina | United States | 27710 |
| 134 | Cumberland Research Associates, LLC | Fayetteville | North Carolina | United States | 28304 |
| 135 | Carolina Research | Greenville | North Carolina | United States | 27834 |
| 136 | Wake Research Associates | Raleigh | North Carolina | United States | 27612 |
| 137 | PMG Research of Winston-Salem | Winston-Salem | North Carolina | United States | 27103 |
| 138 | Consultants for Clinical Research | Cincinnati | Ohio | United States | 45249 |
| 139 | MetroHealth Medical Center | Cleveland | Ohio | United States | 44109 |
| 140 | The Ohio University - Gastroenterology, Hepatology | Columbus | Ohio | United States | 43210 |
| 141 | Digestive Disease Specialist, Inc. | Oklahoma City | Oklahoma | United States | 73112 |
| 142 | Options Health Research | Tulsa | Oklahoma | United States | 74104 |
| 143 | Eastern Pennsylvania Gastroenterology and Liver Specialist | Bethlehem | Pennsylvania | United States | 18017 |
| 144 | UPMC -Center for Liver Diseases | Pittsburgh | Pennsylvania | United States | 15213 |
| 145 | VA Pittsburgh Healthcare System | Pittsburgh | Pennsylvania | United States | 15240 |
| 146 | Care Access Research, Pottsville | Pottsville | Pennsylvania | United States | 17901 |
| 147 | Digestive Disease Associates, LTD | Wyomissing | Pennsylvania | United States | 19610 |
| 148 | Partners in Clinical Research | Cumberland | Rhode Island | United States | 02864 |
| 149 | University Medical Group | North Providence | Rhode Island | United States | 02908 |
| 150 | Care Access Research-Warwick | Warwick | Rhode Island | United States | 02886 |
| 151 | Rapid City Medical Center | Rapid City | South Dakota | United States | 57701 |
| 152 | Mount Vernon Clinical Research | Chattanooga | Tennessee | United States | 37421 |
| 153 | Gastro One | Germantown | Tennessee | United States | 38138 |
| 154 | Digestive Health Research | Hermitage | Tennessee | United States | 37076 |
| 155 | East Tennessee Research Institute | Johnson City | Tennessee | United States | 37604 |
| 156 | Digestive Health Research | Lebanon | Tennessee | United States | 37090 |
| 157 | UT-Memphis, Methodist University Hospital | Memphis | Tennessee | United States | 38104 |
| 158 | Vanderbilt University | Nashville | Tennessee | United States | 37232-1610 |
| 159 | Texas Clinical Research Institute | Arlington | Texas | United States | 76012 |
| 160 | Methodist Dallas Medical Center | Dallas | Texas | United States | 75203 |
| 161 | Liver Center of Texas | Dallas | Texas | United States | 75234 |
| 162 | Synexus | Dallas | Texas | United States | 75234 |
| 163 | University of Texas Southwestern Medical Center | Dallas | Texas | United States | 75390 |
| 164 | San Antonio Military Medical Center | Fort Sam Houston | Texas | United States | 78234 |
| 165 | Baylor Scott & White All Saints Medical Center - Ft. Worth | Fort Worth | Texas | United States | 76104 |
| 166 | Texas Digestive Disease Consultants - Fort Worth | Fort Worth | Texas | United States | 76104 |
| 167 | Digestive Health Associates of Texas-Rockwall | Garland | Texas | United States | 75044 |
| 168 | Therapeutic Concepts, PA | Houston | Texas | United States | 77004 |
| 169 | Pioneer Research Solutions, Inc. | Houston | Texas | United States | 77009 |
| 170 | Liver Associates of Texas | Houston | Texas | United States | 77030-3002 |
| 171 | Baylor College of Medicine | Houston | Texas | United States | 77030 |
| 172 | Michael E. DeBakey VA Medical Center (MEDVAMC) | Houston | Texas | United States | 77030 |
| 173 | St. Luke's Medical Center | Houston | Texas | United States | 77030 |
| 174 | Biopharma Informatic, LLC | Houston | Texas | United States | 77043 |
| 175 | Centex Studies | Houston | Texas | United States | 77058 |
| 176 | Biopharma Informatic, LLC | Houston | Texas | United States | 77084 |
| 177 | Amir Ali Hassan, MD, PA | Houston | Texas | United States | 77089 |
| 178 | Centex Studies, Inc. | McAllen | Texas | United States | 78504 |
| 179 | LinQ Research, LLC | Pearland | Texas | United States | 77584 |
| 180 | Quality Research Inc. | San Antonio | Texas | United States | 78209 |
| 181 | American Research Corporation | San Antonio | Texas | United States | 78215 |
| 182 | Clinical Trials of Texas Inc | San Antonio | Texas | United States | 78229 |
| 183 | Diabetes & Glandular Disease Clinic, P.A. (DGD) | San Antonio | Texas | United States | 78229 |
| 184 | Endeavor Clinical Trials, LLC | San Antonio | Texas | United States | 78229 |
| 185 | Southern Star Research Institute, LLC SAGACT PLLC. | San Antonio | Texas | United States | 78229 |
| 186 | Anson Medicine | San Antonio | Texas | United States | 78260 |
| 187 | Mount Olympus Medical Research, LLC | Sugar Land | Texas | United States | 77479 |
| 188 | Texas Digestive Disease Consultants | Webster | Texas | United States | 77598 |
| 189 | Physician's Research Options, LLC | Draper | Utah | United States | 84020 |
| 190 | Intermountain Medical Center | Murray | Utah | United States | 84107 |
| 191 | Advanced Clinical Research - Center for Digestive Health | Riverton | Utah | United States | 84065 |
| 192 | University of Utah | Salt Lake City | Utah | United States | 84132 |
| 193 | Gastroenterology Associates of Northern Virginia | Fairfax | Virginia | United States | 22031 |
| 194 | Inova Fairfax Medical Campus | Falls Church | Virginia | United States | 22042 |
| 195 | Liver Institute of Virginia | Newport News | Virginia | United States | 23602 |
| 196 | Digestive and Liver Disease Specialists | Norfolk | Virginia | United States | 23502 |
| 197 | McGuire Veterans Affairs Medical Center | Richmond | Virginia | United States | 23249 |
| 198 | VCU Medical Center | Richmond | Virginia | United States | 23298 |
| 199 | Gastroenterology Consultants of Southwest Virginia Research | Roanoke | Virginia | United States | 24014 |
| 200 | Harborview Medical Center | Seattle | Washington | United States | 98104 |
| 201 | Swedish Medical Center | Seattle | Washington | United States | 98104 |
| 202 | Liver Institute Northwest | Seattle | Washington | United States | 98105 |
| 203 | University of Washington Medical Center | Seattle | Washington | United States | 98195 |
| 204 | Marshall University Joan C. Edwards School of Medicine | Huntington | West Virginia | United States | 25701 |
| 205 | Royal Prince Alfred Hospital | Camperdown | New South Wales | Australia | 2050 |
| 206 | Saint George Hospital | Kogarah | New South Wales | Australia | 2217 |
| 207 | Royal Brisbane and Women's Hospital | Herston | Queensland | Australia | 4029 |
| 208 | Royal Adelaide Hospital | Adelaide | South Australia | Australia | 5000 |
| 209 | Flinders Medical Center | Adelaide | South Australia | Australia | 5042 |
| 210 | Monash Medical Centre | Clayton | Victoria | Australia | 3168 |
| 211 | Austin Health | Heidelberg | Victoria | Australia | 3084 |
| 212 | Royal Perth Hospital | Perth | Western Australia | Australia | 6000 |
| 213 | Universitatsklinik far Innere Medizin | Graz | Styria | Austria | 8036 |
| 214 | Universitatsklinik far Innere Medizin II | Innsbruck | Tyrol | Austria | 6020 |
| 215 | Klinikum Wels-Grieskirchen | Wels | Upper Austria | Austria | 4600 |
| 216 | Universitair Ziekenhuis Antwerpen | Edegem | Antwerpen | Belgium | 2650 |
| 217 | Hôpital Erasme | Bruxelles | Brussels | Belgium | 1070 |
| 218 | Algemeen Ziekenhuis Maria Middelares | Gent | Oost-Vlaanderen | Belgium | 9000 |
| 219 | Universitair Ziekenhuis Gent | Gent | Oost-Vlaanderen | Belgium | 9000 |
| 220 | Cliniques Universitaires Saint-Luc | Brussels | Belgium | 1200 | |
| 221 | Centre Hospitalier Chretien CHC | Liege | Belgium | 4000 | |
| 222 | Hospital das Clínicas da Universidade Federal de Minas Gerais | Belo Horizonte | Minas Gerais | Brazil | 30130-100 |
| 223 | Faculdade de Medicina de São José do Rio Preto Hospital de Base | São José do Rio Preto | Sao Paulo | Brazil | 15090-000 |
| 224 | Hospital Universitário Clementino Fraga Filho | Rio de Janeiro | Brazil | 21941-913 | |
| 225 | Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo | Sao Paulo | Brazil | 05403-000 | |
| 226 | University of Calgary Liver Unit | Calgary | Alberta | Canada | T2N 4Z6 |
| 227 | Bailey Health Clinic | Edmonton | Alberta | Canada | T5H 4B9 |
| 228 | Vancouver General Hospital | Vancouver | British Columbia | Canada | V5Z 1M9 |
| 229 | William Osler Health Centre, Brampton Memorial Hospital Campus | Brampton | Ontario | Canada | L6R 3J7 |
| 230 | Toronto Liver Centre | Toronto | Ontario | Canada | M6H 3M1 |
| 231 | Ecogene-21 | Chicoutimi | Quebec | Canada | G7H 7K9 |
| 232 | Centro de Investigaciones Clínicas Viña del Mar | Viña del Mar | Valparaiso | Chile | 2540488 |
| 233 | CHU de Strasbourg | Strasbourg cedex | Alsace | France | 67091 |
| 234 | CHU De Bordeaux - Hôpital Haût-Lévèque CMC Magellan Unita de Recherche Clinique | Pessac | Aquitaine | France | 33604 |
| 235 | Centre Hospitalier Universitaire Estaing | Clermont-Ferrand | Aubergne | France | 63003 |
| 236 | Centre Hospitalier Universitaire de Rennes- Hôpital Pontchaillou | Rennes | Bretagne | France | 35033 |
| 237 | Centre Hospitalier Regional et Universitaire de Besancon - L'Hopital Jean Minjoz | Besançon cedex | Franche-Comte | France | 25030 |
| 238 | Departement d'Hacpatologie | Clichy | Ile-De-France | France | 92110 |
| 239 | Hôpital Saint Antoine | Paris Cedex 12 | Ile-de-France | France | 75571 |
| 240 | CHU de Montpellier | Montpellier cedex 5 | Languedoc-Roussillon | France | 34295 |
| 241 | Centre Hospitalier Universitaire de Rouen CHU de Rouen Hopital Charles-Nicolle | Rouen | Normandie | France | 76000 |
| 242 | Center Hospitalier Universitaire d'Angers | Angers | Pays De La Loire | France | 49000 |
| 243 | Hapital Sud Service d'Hepato- Gastroentarologie | Amiens Cedex 1 | Picardie | France | 80054 |
| 244 | Centre Hospitalier Universitaire de Nice Hôpital l'Archet | Nice Cedex 3 | Provence Alpes Cote D'Azur | France | 06202 |
| 245 | Centre Hospitalier Universitaire Grenoble | Grenoble Cedex 09 | Rhone-Alpes | France | 38700 |
| 246 | Hopital Avicenne | Bobigny | France | 93000 | |
| 247 | Synexus Clinical Research GmbH, Prüfzentrum Frankfurt | Frankfurt | Hessen | Germany | 60313 |
| 248 | Philipps-Universität und Universitätsklinikum Gießen und Marburg GmbH | Marburg | Hessen | Germany | 35043 |
| 249 | Medizinische Hochschule Hannover | Hannover | Niedersachsen | Germany | 30625 |
| 250 | Gastroenterologische Gemeinschaftspraxis | Herne | Nordhein-Westfalen | Germany | 44623 |
| 251 | Uniklinik RWTH Aachen | Aachen | Nordrhein-Westfalen | Germany | 52074 |
| 252 | Uniklinik Köln | Köln | Nordrhein-westfalen | Germany | 50937 |
| 253 | Universitätsmedizin der Johannes Gutenberg Universität Mainz | Mainz | Rheinland-Pfalz | Germany | 55131 |
| 254 | Universitätsklinikum des Saarlandes | Homburg | Saarland | Germany | 66427 |
| 255 | Universitätsklinikum Leipzig | Leipzig | Sachsen | Germany | 04103 |
| 256 | Praxis Driesener Strasse | Berlin | Germany | 10439 | |
| 257 | Synexus Clinical Research GmbH, Prüfzentrum Berlin | Berlin | Germany | 12627 | |
| 258 | Charité Universitätsmedizin Berlin | Berlin | Germany | 13353 | |
| 259 | Universitätsklinikum Hamburg Eppendorf | Hamburg | Germany | 20246 | |
| 260 | Thomopoulos Gastroenterology Dept. | Patra | Peloponnese | Greece | 26504 |
| 261 | Hippokratio Hospital | Thessaloniki | Greece | 54642 | |
| 262 | Prince of Wales Hospital | Shatin | New Territories | Hong Kong | 00852 |
| 263 | Alice Ho Miu Ling Nethersole Hospital | Shatin | New Territories | Hong Kong | |
| 264 | Somogy Megyei Kaposi Mór Oktató Kórház | Kaposvár | Somogy | Hungary | 7400-7400 |
| 265 | SYNEXUS Magyarország Kft. - Budapest DRS | Budapest | Hungary | 1036 | |
| 266 | Synexus Magyarorszag Egeszsegugyi Szolgaltato Kft | Debrecen | Hungary | 4025 | |
| 267 | EMMS MC | Nazareth | Jerusalem | Israel | 91031 |
| 268 | Rambam Health Care Campus - Rambam Medical Center | Haifa | Israel | 31999 | |
| 269 | Carmel Medical Center | Haifa | Israel | 34362 | |
| 270 | Shaare Zedek Medical Center | Jerusalem | Israel | 91031 | |
| 271 | Hadassah Medical Center, Institute of Gastroenterology and Liver Diseases | Jerusalem | Israel | 91120 | |
| 272 | Galilee Medical Center | Nahariya | Israel | 22100 | |
| 273 | Rabin Medical Center Beilinson Hospital | Petah Tikva | Israel | 49100 | |
| 274 | Tel Aviv Sourasky Medical Center | Tel Aviv | Israel | 64239 | |
| 275 | Sheba Medical Center | Tel-Hashomer | Israel | 52621 | |
| 276 | Ospedale Casa Sollievo della Sofferenza | San Giovanni Rotondo | Foggia | Italy | 71013 |
| 277 | ASST Grande Ospedale Metropolitano Niguarda | Milan | Milano | Italy | 20162 |
| 278 | Istituto Clinico Humanitas | Rozzano | Milano | Italy | 20089 |
| 279 | Azienda Ospedaliera Universitaria Careggi SOD Medicina Interna ed Epatologia | Firenze | Italy | 50134 | |
| 280 | ASST Santi Paolo e Carlo | Milano | Italy | 20142 | |
| 281 | Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone | Palermo | Italy | 90127 | |
| 282 | Fondazione Policlinico Tor Vergata | Roma | Italy | 00133 | |
| 283 | Fondazione Policlinico Universitario Agostino Gemelli | Roma | Italy | 00168 | |
| 284 | Pauls Stradins Clinical University Hospital | Riga | Latvia | LV-1002-1002 | |
| 285 | Consultorio Médico Dr. Alma Laura Ladron de Guevara | Mexico | Distrito Federal | Mexico | 06700 |
| 286 | JM Research - Cuernavaca | Cuernavaca | Morelos | Mexico | 62290 |
| 287 | Investigaciones Medicas Cisneros | Monterrey | Nuevo Leon | Mexico | 64000 |
| 288 | Consultorio Dra. Maria Sarai Gonzalez Huezo | Metepec | Mexico | 52140 | |
| 289 | Auckland City Hospital | Grafton | Auckland | New Zealand | 1023 |
| 290 | Middlemore Clinical Trials | Papatoetoe | Auckland | New Zealand | 2025 |
| 291 | Oslo Universitetssykehus-Ullevål | Oslo | Norway | 0450 | |
| 292 | Centrum Badan Klinicznych Piotr Napora Lekarze Spólka Partnerska | Wroclaw | Dolnoslaskie | Poland | 51-162 |
| 293 | EMC Instytut Medyczny | Wroclaw | Dolnoslaskie | Poland | 54-144 |
| 294 | Wojewódzki Specjalistyczny Szpital im. dr Wl. Bieganskiego w Lodzi | Lódz | Lodzkie | Poland | 91-347 |
| 295 | Synexus Polska Sp. z o.o. Oddział w Łodzi | Łódź | Lodz | Poland | 90-127 |
| 296 | Szpital Specjalistyczny Nr 1 w Bytomiu | Bytom | Slaskie | Poland | 41-902 |
| 297 | ID Clinic Arkadiusz Pisula | Myslowice | Slaskie | Poland | 41400-400 |
| 298 | Synexus Polska Sp z o o Oddzial w Poznaniu | Poznań | Wielkopolska | Poland | 60 702-702 |
| 299 | Synexus Polska Sp. z o.o. Oddzial we Wroclawiu | Wrocław | Wroclaw | Poland | 50-381 |
| 300 | Synexus Polska Sp. Z o.o. Oddzial w Czestochowie | Czestochowa | Poland | 0 42-202 | |
| 301 | Synexus Polska Sp. z o.o. Oddzial w Gdansku | Gdańsk | Poland | 80-382 | |
| 302 | Synexus Polska Sp. z o.o. Oddzial w Gdyni ul. | Gdynia | Poland | 81-537 | |
| 303 | Synexus SCM Sp. z o.o. Oddzial | Katowice | Poland | 40-040 | |
| 304 | Synexus Polska Sp. z o.o. Oddział w Warszawie | Warsaw | Poland | 01-192 | |
| 305 | Presa-Ramos | Vila Real | Lordelo | Portugal | 5000-508 |
| 306 | Unidade Local de Saúde do Alto Minho | Viana do Castelo | Portugal | 4904-858 | |
| 307 | Clinical Research Puerto Rico | San Juan | Puerto Rico | 00909-1711 | |
| 308 | Fundacion de Investigacion De Diego | San Juan | Puerto Rico | 00927 | |
| 309 | Institutul Regional de Gastroenterologie si Hepatologie Prof. Dr. O Fodor | Cluj-Napoca | Cluj | Romania | 400162 |
| 310 | Clinic Professor Gorbakova | Krasnogorsk | Moscow | Russian Federation | 143405 |
| 311 | Sklifosovsky Scientific Research Institution of Emergency Care | Moscow | Russian Federation | 129090 | |
| 312 | Moscow Regional Research and Clinical Institute M.F. Vladimirsky | Moscow | Russian Federation | 129110 | |
| 313 | National University Hospital | Singapore | Singapore | 119082 | |
| 314 | Hospital Universitari Germans Trias i Pujol | Badalona | Barcelona | Spain | 08916 |
| 315 | Hospital Universitario Donostia | San Sebastian | Guipuzcoa | Spain | 20014 |
| 316 | Complejo Hospitalario Torrecardenas | Almeria | Spain | 4009 | |
| 317 | Hospital del Mar | Barcelona | Spain | 08003 | |
| 318 | Hospital Universitari Vall d'Hebrón | Barcelona | Spain | 08035 | |
| 319 | Hospital General Universitario Gregorio Marañon | Madrid | Spain | 28007 | |
| 320 | Hospital Universitario Ramón Y Cajal | Madrid | Spain | 28034 | |
| 321 | Hospital Clínico Universitario Virgen de la Victoria | Málaga | Spain | 29010 | |
| 322 | Hospital Universitario Marqués de Valdecilla | Santander | Spain | 39008 | |
| 323 | Hospital Universitario Virgen del Rocio | Sevilla | Spain | 41013 | |
| 324 | Hospital Universitario Nuestra Senora de Valme | Sevilla | Spain | 41014 | |
| 325 | Consorci Hospital General Universitari de València | Valencia | Spain | 46014 | |
| 326 | Hospital Universitari i Politecnic La Fe de Valencia | Valencia | Spain | 46026 | |
| 327 | Kantonsspital St.Gallen Klinik für | St. Gallen | Saint Gallen | Switzerland | 9007 |
| 328 | Universitaetsspital Bern Inselspital | Bern | Switzerland | 3010 | |
| 329 | Chia-Yi Christian Hospital | Chiayi City | Chiayi | Taiwan | 60002 |
| 330 | China Medical University Hospital | Taichung | Taichung City | Taiwan | 404 |
| 331 | Chang Gung Medical Foundation-LinKou Branch | Taoyuan | Taiwan | 333 | |
| 332 | University Hospitals Birmingham NHS Foundation Trust | Birmingham | England | United Kingdom | B15 2TH |
| 333 | Hull and East Yorkshire Hospitals NHS Trust | Hull | England | United Kingdom | HU3 2JZ |
| 334 | Royal Free London NHS Foundation Trust | London | England | United Kingdom | NW3 2QG |
| 335 | Kings College Hospital NHS Foundation Trust | London | England | United Kingdom | SE5 9RS |
| 336 | Chelsea and Westminster Hospital NHS Foundation Trust | London | England | United Kingdom | SW10 9NH |
| 337 | Luton and Dunstable Hospital NHS Foundation Trust | Luton | England | United Kingdom | LU4 0DZ |
| 338 | Newcastle Upon the Tyne Hospitals | Newcastle | England | United Kingdom | NE2 7DN |
| 339 | Nottingham Digestive Diseases Biomedical Research Unit | Nottingham | England | United Kingdom | NG7 2UH |
| 340 | Plymouth Hospitals NHS Trust | Plymouth | England | United Kingdom | PL6 8DH |
| 341 | Royal Stoke University Hospital | Stoke-on-Trent | England | United Kingdom | ST4 6QG |
| 342 | St James's University Hospital | Leeds | West Yorkshire | United Kingdom | LS97TF |
| 343 | Synexus Hexham Clinical Research Centre | Hexham | United Kingdom | NE46 1QJ | |
| 344 | Synexus Lancashire Clinical Research Centre | Lancaster | United Kingdom | PR7 7NA | |
| 345 | Barts Health NHS Trust The Royal London Hospital | London | United Kingdom | E1 1BB | |
| 346 | University Hospital of South Manchester NHS Foundation Trust | Manchester | United Kingdom | M23 9LT |
Sponsors and Collaborators
- Tobira Therapeutics, Inc.
Investigators
- Study Director: Gerardo Rodriguez, Allergan
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Tobira Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT03028740
Other Study ID Numbers:
- 3152-301-002
- 2016-004566-26
- 1001
First Posted:
Jan 23, 2017
Last Update Posted:
Mar 10, 2022
Last Verified:
Nov 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 1778 participants were randomized into the study, of which 1293 participated in Part 1 of the study. The study was terminated early, and Part 2 did not enroll the planned number of participants. Therefore, the Part 1 and Part 2 data were combined and reported as the Full Study Cohort for reporting of the Part 2 efficacy endpoints and the safety endpoints. |
| Arm/Group Title | Placebo | Cenicriviroc 150 mg |
|---|---|---|
| Arm/Group Description | Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months. | Participants received cenicriviroc, 150 milligrams (mg), tablet, orally, once daily for up to approximately 40 months. |
| Period Title: Overall Study | ||
| STARTED | 593 | 1185 |
| Full Study Cohort: Received Study Drug | 589 | 1180 |
| Participated in Part 1 | 432 | 861 |
| Part 1: Received Study Drug | 429 | 859 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 593 | 1185 |
Baseline Characteristics
| Arm/Group Title | Placebo | Cenicriviroc 150 mg | Total |
|---|---|---|---|
| Arm/Group Description | Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months. | Participants received cenicriviroc,150 mg, tablet, orally, once daily for up to approximately 40 months. | Total of all reporting groups |
| Overall Participants | 589 | 1180 | 1769 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
55.8
(11.04)
|
55.2
(10.76)
|
55.4
(10.86)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
354
60.1%
|
749
63.5%
|
1103
62.4%
|
| Male |
235
39.9%
|
431
36.5%
|
666
37.6%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
172
29.2%
|
315
26.7%
|
487
27.5%
|
| Not Hispanic or Latino |
417
70.8%
|
865
73.3%
|
1282
72.5%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
7
1.2%
|
8
0.7%
|
15
0.8%
|
| Asian |
22
3.7%
|
45
3.8%
|
67
3.8%
|
| Native Hawaiian or Other Pacific Islander |
2
0.3%
|
7
0.6%
|
9
0.5%
|
| Black or African American |
14
2.4%
|
38
3.2%
|
52
2.9%
|
| White |
539
91.5%
|
1075
91.1%
|
1614
91.2%
|
| More than one race |
3
0.5%
|
6
0.5%
|
9
0.5%
|
| Unknown or Not Reported |
2
0.3%
|
1
0.1%
|
3
0.2%
|
Outcome Measures
| Title | Part 1: Percentage of Participants With Improvement in Fibrosis by at Least 1 Stage and No Worsening of Steatohepatitis on Liver Histology at Month 12 |
|---|---|
| Description | Fibrosis stage was evaluated using the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Staging System with stages: 0=none; 1=perisinusoidal or periportal; 1A=mild, zone 3, perisinusoidal; 1B=moderate, zone 3, perisinusoidal; 1C=portal/periportal; 2=perisinusoidal and portal/periportal; 3=bridging fibrosis; 4=cirrhosis. No worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade as per scoring in relevant nonalcoholic fatty liver disease activity score (NAS) categories. NAS is a semiquantitative scoring system based on the unweighted sum of: steatosis (0=<5% to 3=>66%), lobular inflammation (0=no foci to 3=>4 foci/200x), and hepatocellular ballooning (0=none to 2=many cells/prominent ballooning) scores. Improvement in fibrosis is a decrease in the NASH CRN fibrosis stage. |
| Time Frame | Month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT Population for Part 1 included participants randomly assigned to a treatment group who received at least one dose of study drug in Part 1. |
| Arm/Group Title | Placebo | Cenicriviroc 150 mg |
|---|---|---|
| Arm/Group Description | Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months. | Participants received cenicriviroc,150 mg, tablet, orally, once daily for up to approximately 40 months. |
| Measure Participants | 429 | 859 |
| Number (95% Confidence Interval) [percentage of participants] |
25.5
4.3%
|
22.3
1.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Cenicriviroc 150 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2067 |
| Comments | P-value was based on Cochran-Mantel-Haenszel general association test comparing Cenicriviroc vs Placebo, controlling for factors (randomization strata: fibrosis stage [2 vs 3] and presence or absence of Type 2 diabetes mellitus (T2DM) at Baseline). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -3.2 | |
| Confidence Interval |
(2-Sided) 95% -8.2 to 1.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Cenicriviroc 150 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.8369 | |
| Confidence Interval |
(2-Sided) 95% 0.6341 to 1.1044 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Odds Ratio was based on Mantel-Haenszel estimates comparing Cenicriviroc vs Placebo, controlling for factors (randomization strata: fibrosis stage [2 vs 3] and presence or absence of T2DM at Baseline). | |
| Title | Time to First Occurrence of Adjudicated Events in the Full Study Cohort |
|---|---|
| Description | Time to first occurrence from Baseline was defined as the number of days from the first dose of randomized investigational product to the onset of the first occurrence of any of the following adjudicated events: death (all cause), histopathologic progression to cirrhosis, liver transplant, model for end stage liver disease (MELD) score ≥15, ascites, hospitalization for onset of: variceal bleed, hepatic encephalopathy, spontaneous bacterial peritonitis. MELD is a scoring system for assessing the severity of chronic liver disease and uses the participant's values for total bilirubin, serum creatinine, and the international normalized ratio for prothrombin time to predict survival. MELD score ranges from 6 (less ill) to 40 (gravely ill) with scores and mortality probability being: Score 40=71.3% mortality; Scores 30-39=52.6% mortality; Scores 20-29=19.6% mortality; Scores10-19=6.0% mortality; Score 9 or less=1.9% mortality. |
| Time Frame | From first dose of study drug to onset of first occurrence of the event (Up to approximately 42 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT Population for the full study cohort included participants randomly assigned to a treatment group who received at least one dose of study drug in Parts 1 and 2 of the study combined. |
| Arm/Group Title | Placebo | Cenicriviroc 150 mg |
|---|---|---|
| Arm/Group Description | Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months. | Participants received cenicriviroc,150 mg, tablet, orally, once daily for up to approximately 40 months. |
| Measure Participants | 589 | 1180 |
| Median (95% Confidence Interval) [days] |
NA
|
NA
|
| Title | Part 1: Percentage of Participants With Improvement in Fibrosis by at Least 2 Stages and No Worsening of Steatohepatitis on Liver Histology at Month 12 |
|---|---|
| Description | Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages: 0=none; 1=perisinusoidal or periportal; 1A=mild, zone 3, perisinusoidal; 1B=moderate, zone 3, perisinusoidal; 1C=portal/periportal; 2=perisinusoidal and portal/periportal; 3=bridging fibrosis; 4=cirrhosis. No worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade as per scoring in relevant NAS categories. NAS is a semiquantitative scoring system based on the unweighted sum of: steatosis (0=<5% to 3=>66%), lobular inflammation (0=no foci to 3=>4 foci/200x), and hepatocellular ballooning (0=none to 2=many cells/prominent ballooning) scores. Improvement in fibrosis is a decrease in the NASH CRN fibrosis stage. |
| Time Frame | Month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT Population for Part 1 included participants randomly assigned to a treatment group who received at least one dose of study drug in Part 1. |
| Arm/Group Title | Placebo | Cenicriviroc 150 mg |
|---|---|---|
| Arm/Group Description | Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months. | Participants received cenicriviroc,150 mg, tablet, orally, once daily for up to approximately 40 months. |
| Measure Participants | 429 | 859 |
| Number (95% Confidence Interval) [percentage of participants] |
8.3
1.4%
|
6.6
0.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Cenicriviroc 150 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2827 |
| Comments | P-value was based on Cochran-Mantel-Haenszel general association test comparing Cenicriviroc vs Placebo, controlling for factors (randomization strata: fibrosis stage [2 vs 3] and presence or absence of T2DM at Baseline). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -1.7 | |
| Confidence Interval |
(2-Sided) 95% -4.8 to 1.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Cenicriviroc 150 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.7844 | |
| Confidence Interval |
(2-Sided) 95% 0.5032 to 1.2229 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Odds Ratio was based on Mantel-Haenszel estimates comparing Cenicriviroc vs Placebo, controlling for factors (randomization strata: fibrosis stage [2 vs 3] and presence or absence of T2DM at Baseline). | |
| Title | Part 1: Percentage of Participants With Improvement in Fibrosis by at Least 1 Stage Regardless of Effect on Steatohepatitis at Month 12 |
|---|---|
| Description | Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages 0=none, 1=perisinusoidal or periportal, 1A=mild, zone 3, perisinusoidal, 1B=moderate, zone 3, perisinusoidal, 1C=portal/periportal, 2=perisinusoidal and portal/periportal, 3=bridging fibrosis, 4=cirrhosis. |
| Time Frame | Month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT Population for Part 1 included participants randomly assigned to a treatment group who received at least one dose of study drug in Part 1. Overall number analyzed is the number of participants with data available for analyses. |
| Arm/Group Title | Placebo | Cenicriviroc 150 mg |
|---|---|---|
| Arm/Group Description | Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months. | Participants received cenicriviroc, 150 mg, tablet, orally, once daily for up to approximately 40 months. |
| Measure Participants | 348 | 692 |
| Number (95% Confidence Interval) [percentage of participants] |
33.3
5.7%
|
30.6
2.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Cenicriviroc 150 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4054 |
| Comments | P-value was based on Cochran-Mantel-Haenszel general association test comparing Cenicriviroc vs Placebo, controlling for factors (randomization strata: fibrosis stage [2 vs 3] and presence or absence of T2DM at Baseline). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Difference |
| Estimated Value | -2.7 | |
| Confidence Interval |
(2-Sided) 95% -8.7 to 3.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Cenicriviroc 150 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.8877 | |
| Confidence Interval |
(2-Sided) 95% 0.6709 to 1.1744 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Odds Ratio was based on Mantel-Haenszel estimates comparing Cenicriviroc vs Placebo, controlling for factors (randomization strata: fibrosis stage [2 vs 3] and presence or absence of T2DM at Baseline). | |
| Title | Part 1: Percentage of Participants With Improvement in Fibrosis by at Least 2 Stages Regardless of Effect on Steatohepatitis at Month 12 |
|---|---|
| Description | Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages 0=none, 1=perisinusoidal or periportal, 1A=mild, zone 3, perisinusoidal, 1B=moderate, zone 3, perisinusoidal, 1C=portal/periportal, 2=perisinusoidal and portal/periportal, 3=bridging fibrosis, 4=cirrhosis. |
| Time Frame | Month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT Population for Part 1 included participants randomly assigned to a treatment group who received at least one dose of study drug in Part 1. Overall number analyzed is the number of participants with data available for analyses. |
| Arm/Group Title | Placebo | Cenicriviroc 150 mg |
|---|---|---|
| Arm/Group Description | Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months. | Participants received cenicriviroc, 150 mg, tablet, orally, once daily for up to approximately 40 months. |
| Measure Participants | 348 | 692 |
| Number [percentage of participants] |
10.3
1.7%
|
8.8
0.7%
|
| Title | Percentage of Participants With Improvement in Fibrosis by at Least 1 Stage and No Worsening of Steatohepatitis on Liver Biopsy at Month 12 in the Full Study Cohort |
|---|---|
| Description | Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages: 0=none; 1=perisinusoidal or periportal; 1A=mild, zone 3, perisinusoidal; 1B=moderate, zone 3, perisinusoidal; 1C=portal/periportal; 2=perisinusoidal and portal/periportal; 3=bridging fibrosis; 4=cirrhosis. No worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade as per scoring in relevant NAS categories. NAS is a semiquantitative scoring system based on the unweighted sum of: steatosis (0=<5% to 3=>66%), lobular inflammation (0=no foci to 3=>4 foci/200x), and hepatocellular ballooning (0=none to 2=many cells/prominent ballooning) scores. Improvement in fibrosis is a decrease in the NASH CRN fibrosis stage. |
| Time Frame | Month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT Population for the full study cohort included participants randomly assigned to a treatment group who received at least one dose of study drug in Parts 1 and 2 of the study combined. |
| Arm/Group Title | Placebo | Cenicriviroc 150 mg |
|---|---|---|
| Arm/Group Description | Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months. | Participants received cenicriviroc,150 mg, tablet, orally, once daily for up to approximately 40 months. |
| Measure Participants | 589 | 1180 |
| Number (95% Confidence Interval) [percentage of participants] |
25.0
4.2%
|
22.0
1.9%
|
| Title | Percentage of Participants With Improvement in Fibrosis by at Least 1 Stage Regardless of Effect on Steatohepatitis on Liver Biopsy at Month 12 in the Full Study Cohort |
|---|---|
| Description | Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages 0=none, 1=perisinusoidal or periportal, 1A=mild, zone 3, perisinusoidal, 1B=moderate, zone 3, perisinusoidal, 1C=portal/periportal, 2=perisinusoidal and portal/periportal, 3=bridging fibrosis, 4=cirrhosis. |
| Time Frame | Month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT Population for the full study cohort included participants randomly assigned to a treatment group who received at least one dose of study drug in Parts 1 and 2 of the study combined. Overall number analyzed is the number of participants with data available for analyses. |
| Arm/Group Title | Drug: Placebo | Drug: Cenicriviroc 150 mg |
|---|---|---|
| Arm/Group Description | Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months. | Participants received cenicriviroc, 150 mg, tablet, orally, once daily for up to approximately 40 months. |
| Measure Participants | 373 | 741 |
| Number (95% Confidence Interval) [percentage of participants] |
33.2
5.6%
|
30.5
2.6%
|
| Title | Percentage of Participants With Improvement in Fibrosis by at Least 2 Stages and No Worsening of Steatohepatitis on Liver Biopsy at Month 12 in the Full Study Cohort |
|---|---|
| Description | Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages: 0=none; 1=perisinusoidal or periportal; 1A=mild, zone 3, perisinusoidal; 1B=moderate, zone 3, perisinusoidal; 1C=portal/periportal; 2=perisinusoidal and portal/periportal; 3=bridging fibrosis; 4=cirrhosis. No worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade as per scoring in relevant NAS categories. NAS is a semiquantitative scoring system based on the unweighted sum of: steatosis (0=<5% to 3=>66%), lobular inflammation (0=no foci to 3=>4 foci/200x), and hepatocellular ballooning (0=none to 2=many cells/prominent ballooning) scores. Improvement in fibrosis is a decrease in the NASH CRN fibrosis stage. |
| Time Frame | Month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT Population for the full study cohort included participants randomly assigned to a treatment group who received at least one dose of study drug for Parts 1 and 2 of the study combined. |
| Arm/Group Title | Placebo | Cenicriviroc 150 mg |
|---|---|---|
| Arm/Group Description | Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months. | Participants received cenicriviroc,150 mg, tablet, orally, once daily for up to approximately 40 months. |
| Measure Participants | 589 | 1180 |
| Number (95% Confidence Interval) [percentage of participants] |
8.3
1.4%
|
6.8
0.6%
|
| Title | Percentage of Participants With Improvement in Fibrosis by at Least 2 Stages Regardless of Effect on Steatohepatitis on Liver Biopsy at Month 12 in the Full Study Cohort |
|---|---|
| Description | Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages 0=none, 1=perisinusoidal or periportal, 1A=mild, zone 3, perisinusoidal, 1B=moderate, zone 3, perisinusoidal, 1C=portal/periportal, 2=perisinusoidal and portal/periportal, 3=bridging fibrosis, 4=cirrhosis. |
| Time Frame | Month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT Population for the full study cohort included participants randomly assigned to a treatment group who received at least one dose of study drug in Parts 1 and 2 of the study combined. Overall number analyzed is the number of participants with data available for analyses. |
| Arm/Group Title | Placebo | Cenicriviroc 150 mg |
|---|---|---|
| Arm/Group Description | Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months. | Participants received cenicriviroc, 150 mg, tablet, orally, once daily for up to approximately 40 months. |
| Measure Participants | 373 | 741 |
| Number [percentage of participants] |
9.9
1.7%
|
8.9
0.8%
|
| Title | Percentage of Participants With Improvement in Fibrosis by at Least 1 Stage and No Worsening of Steatohepatitis on Liver Biopsy at Month 60 in the Full Study Cohort |
|---|---|
| Description | Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages: 0=none; 1=perisinusoidal or periportal; 1A=mild, zone 3, perisinusoidal; 1B=moderate, zone 3, perisinusoidal; 1C=portal/periportal; 2=perisinusoidal and portal/periportal; 3=bridging fibrosis; 4=cirrhosis. No worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade as per scoring in relevant NAS categories. NAS is a semiquantitative scoring system based on the unweighted sum of: steatosis (0=<5% to 3=>66%), lobular inflammation (0=no foci to 3=>4 foci/200x), and hepatocellular ballooning (0=none to 2=many cells/prominent ballooning) scores. Improvement in fibrosis is a decrease in the NASH CRN fibrosis stage. |
| Time Frame | Month 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| No data was collected as the study was terminated and no participants reached the Month 60 timepoint. |
| Arm/Group Title | Placebo | Cenicriviroc 150 mg |
|---|---|---|
| Arm/Group Description | Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months. | Participants received cenicriviroc, 150 mg, tablet, orally, once daily for up to approximately 40 months. |
| Measure Participants | 0 | 0 |
| Title | Percentage of Participants With Improvement in Fibrosis by at Least 1 Stage Regardless of Effect on Steatohepatitis on Liver Biopsy at Month 60 in the Full Study Cohort |
|---|---|
| Description | Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages 0=none, 1=perisinusoidal or periportal, 1A=mild, zone 3, perisinusoidal, 1B=moderate, zone 3, perisinusoidal, 1C=portal/periportal, 2=perisinusoidal and portal/periportal, 3=bridging fibrosis, 4=cirrhosis. |
| Time Frame | Month 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| No data was collected as the study was terminated and no participants reached the Month 60 timepoint. |
| Arm/Group Title | Placebo | Cenicriviroc 150 mg |
|---|---|---|
| Arm/Group Description | Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months. | Participants received cenicriviroc, 150 mg, tablet, orally, once daily for up to approximately 40 months. |
| Measure Participants | 0 | 0 |
| Title | Percentage of Participants With Improvement in Fibrosis by at Least 2 Stages and No Worsening of Steatohepatitis on Liver Biopsy at Month 60 in the Full Study Cohort |
|---|---|
| Description | Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages: 0=none; 1=perisinusoidal or periportal; 1A=mild, zone 3, perisinusoidal; 1B=moderate, zone 3, perisinusoidal; 1C=portal/periportal; 2=perisinusoidal and portal/periportal; 3=bridging fibrosis; 4=cirrhosis. No worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade as per scoring in relevant NAS categories. NAS is a semiquantitative scoring system based on the unweighted sum of: steatosis (0=<5% to 3=>66%), lobular inflammation (0=no foci to 3=>4 foci/200x), and hepatocellular ballooning (0=none to 2=many cells/prominent ballooning) scores. Improvement in fibrosis is a decrease in the NASH CRN fibrosis stage. |
| Time Frame | Month 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| No data was collected as the study was terminated and no participants reached the Month 60 timepoint. |
| Arm/Group Title | Placebo | Cenicriviroc 150 mg |
|---|---|---|
| Arm/Group Description | Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months. | Participants received cenicriviroc, 150 mg, tablet, orally, once daily for up to approximately 40 months. |
| Measure Participants | 0 | 0 |
| Title | Percentage of Participants With Improvement in Fibrosis by at Least 2 Stages Regardless of Effect on Steatohepatitis on Liver Biopsy at Month 60 in the Full Study Cohort |
|---|---|
| Description | Fibrosis stage was evaluated using NASH CRN Fibrosis Staging System with stages 0=None, 1=Perisinusoidal or periportal, 1A=Mild, zone 3, perisinusoidal, 1B=Moderate, zone 3, perisinusoidal, 1C=Portal/periportal, 2=Perisinusoidal and portal/periportal, 3=Bridging fibrosis, 4=Cirrhosis. |
| Time Frame | Month 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| No data was collected as the study was terminated and no participants reached the Month 60 timepoint. |
| Arm/Group Title | Placebo | Cenicriviroc 150 mg |
|---|---|---|
| Arm/Group Description | Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months. | Participants received cenicriviroc, 150 mg, tablet, orally, once daily for up to approximately 40 months. |
| Measure Participants | 0 | 0 |
Adverse Events
| Time Frame | From first dose through 30 days after the last dose of study drug (Up to approximately 42 months) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | All-cause Mortality: All enrolled participants. Serious Adverse Events and Other Adverse Events: Safety Population for the full study cohort included participants who received at least one dose of study drug in Parts 1 and 2 of the study combined. | |||
| Arm/Group Title | Placebo | Cenicriviroc 150 mg | ||
| Arm/Group Description | Participants received cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months. | Participants received cenicriviroc,150 mg, tablet, orally, once daily for up to approximately 40 months. | ||
All Cause Mortality |
||||
| Placebo | Cenicriviroc 150 mg | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/593 (0.3%) | 6/1185 (0.5%) | ||
Serious Adverse Events |
||||
| Placebo | Cenicriviroc 150 mg | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 70/589 (11.9%) | 159/1180 (13.5%) | ||
| Blood and lymphatic system disorders | ||||
| Blood loss anaemia | 2/589 (0.3%) | 1/1180 (0.1%) | ||
| Anaemia | 0/589 (0%) | 1/1180 (0.1%) | ||
| Immune thrombocytopenia | 0/589 (0%) | 1/1180 (0.1%) | ||
| Lymphadenitis | 0/589 (0%) | 1/1180 (0.1%) | ||
| Lymphadenopathy | 0/589 (0%) | 1/1180 (0.1%) | ||
| Thrombocytopenia | 0/589 (0%) | 1/1180 (0.1%) | ||
| Splenomegaly | 1/589 (0.2%) | 0/1180 (0%) | ||
| Cardiac disorders | ||||
| Acute myocardial infarction | 2/589 (0.3%) | 4/1180 (0.3%) | ||
| Coronary artery disease | 0/589 (0%) | 4/1180 (0.3%) | ||
| Angina pectoris | 0/589 (0%) | 3/1180 (0.3%) | ||
| Atrial fibrillation | 0/589 (0%) | 3/1180 (0.3%) | ||
| Myocardial infarction | 1/589 (0.2%) | 2/1180 (0.2%) | ||
| Acute coronary syndrome | 0/589 (0%) | 2/1180 (0.2%) | ||
| Aortic valve incompetence | 0/589 (0%) | 2/1180 (0.2%) | ||
| Aortic valve disease | 0/589 (0%) | 1/1180 (0.1%) | ||
| Aortic valve disease mixed | 0/589 (0%) | 1/1180 (0.1%) | ||
| Cardiac failure | 0/589 (0%) | 1/1180 (0.1%) | ||
| Cardiac failure congestive | 0/589 (0%) | 1/1180 (0.1%) | ||
| Left ventricular hypertrophy | 0/589 (0%) | 1/1180 (0.1%) | ||
| Mitral valve incompetence | 0/589 (0%) | 1/1180 (0.1%) | ||
| Palpitations | 0/589 (0%) | 1/1180 (0.1%) | ||
| Pulseless electrical activity | 0/589 (0%) | 1/1180 (0.1%) | ||
| Stress cardiomyopathy | 0/589 (0%) | 1/1180 (0.1%) | ||
| Angina unstable | 1/589 (0.2%) | 0/1180 (0%) | ||
| Cardiac arrest | 1/589 (0.2%) | 0/1180 (0%) | ||
| Coronary artery stenosis | 1/589 (0.2%) | 0/1180 (0%) | ||
| Congenital, familial and genetic disorders | ||||
| Phimosis | 0/235 (0%) | 1/431 (0.2%) | ||
| Ear and labyrinth disorders | ||||
| Vertigo | 1/589 (0.2%) | 4/1180 (0.3%) | ||
| Vertigo positional | 1/589 (0.2%) | 0/1180 (0%) | ||
| Endocrine disorders | ||||
| Hypoparathyroidism | 1/589 (0.2%) | 0/1180 (0%) | ||
| Hypothyroidism | 1/589 (0.2%) | 0/1180 (0%) | ||
| Thyroid mass | 1/589 (0.2%) | 0/1180 (0%) | ||
| Eye disorders | ||||
| Visual impairment | 0/589 (0%) | 1/1180 (0.1%) | ||
| Gastrointestinal disorders | ||||
| Pancreatitis acute | 2/589 (0.3%) | 6/1180 (0.5%) | ||
| Colitis | 1/589 (0.2%) | 2/1180 (0.2%) | ||
| Small intestinal obstruction | 0/589 (0%) | 2/1180 (0.2%) | ||
| Abdominal pain | 2/589 (0.3%) | 1/1180 (0.1%) | ||
| Diverticular perforation | 0/589 (0%) | 1/1180 (0.1%) | ||
| Rectal haemorrhage | 0/589 (0%) | 1/1180 (0.1%) | ||
| Vomiting | 0/589 (0%) | 1/1180 (0.1%) | ||
| Abdominal distension | 1/589 (0.2%) | 0/1180 (0%) | ||
| Abdominal hernia | 1/589 (0.2%) | 0/1180 (0%) | ||
| Abdominal pain lower | 1/589 (0.2%) | 0/1180 (0%) | ||
| Alcoholic pancreatitis | 1/589 (0.2%) | 0/1180 (0%) | ||
| Hiatus hernia | 1/589 (0.2%) | 0/1180 (0%) | ||
| Impaired gastric emptying | 1/589 (0.2%) | 0/1180 (0%) | ||
| Mesenteric panniculitis | 1/589 (0.2%) | 0/1180 (0%) | ||
| General disorders | ||||
| Non-cardiac chest pain | 2/589 (0.3%) | 4/1180 (0.3%) | ||
| Fatigue | 0/589 (0%) | 2/1180 (0.2%) | ||
| Chest pain | 1/589 (0.2%) | 1/1180 (0.1%) | ||
| Death | 0/589 (0%) | 1/1180 (0.1%) | ||
| Generalised oedema | 0/589 (0%) | 1/1180 (0.1%) | ||
| Pyrexia | 0/589 (0%) | 1/1180 (0.1%) | ||
| Systemic inflammatory response syndrome | 0/589 (0%) | 1/1180 (0.1%) | ||
| Malaise | 1/589 (0.2%) | 0/1180 (0%) | ||
| Hepatobiliary disorders | ||||
| Autoimmune hepatitis | 0/589 (0%) | 1/1180 (0.1%) | ||
| Cholecystitis acute | 0/589 (0%) | 1/1180 (0.1%) | ||
| Cholelithiasis | 0/589 (0%) | 1/1180 (0.1%) | ||
| Cholecystitis | 2/589 (0.3%) | 0/1180 (0%) | ||
| Hepatic cirrhosis | 1/589 (0.2%) | 0/1180 (0%) | ||
| Non-alcoholic steatohepatitis | 1/589 (0.2%) | 0/1180 (0%) | ||
| Infections and infestations | ||||
| COVID-19 pneumonia | 2/589 (0.3%) | 6/1180 (0.5%) | ||
| Pneumonia | 4/589 (0.7%) | 5/1180 (0.4%) | ||
| COVID-19 | 2/589 (0.3%) | 5/1180 (0.4%) | ||
| Cellulitis | 2/589 (0.3%) | 4/1180 (0.3%) | ||
| Sepsis | 5/589 (0.8%) | 2/1180 (0.2%) | ||
| Diverticulitis | 2/589 (0.3%) | 2/1180 (0.2%) | ||
| Gastroenteritis | 2/589 (0.3%) | 1/1180 (0.1%) | ||
| Pyelonephritis | 2/589 (0.3%) | 1/1180 (0.1%) | ||
| Osteomyelitis | 1/589 (0.2%) | 1/1180 (0.1%) | ||
| Acute sinusitis | 0/589 (0%) | 1/1180 (0.1%) | ||
| Appendicitis | 0/589 (0%) | 1/1180 (0.1%) | ||
| Gallbladder empyema | 0/589 (0%) | 1/1180 (0.1%) | ||
| Gangrene | 0/589 (0%) | 1/1180 (0.1%) | ||
| Influenza | 0/589 (0%) | 1/1180 (0.1%) | ||
| Kidney infection | 0/589 (0%) | 1/1180 (0.1%) | ||
| Post procedural infection | 0/589 (0%) | 1/1180 (0.1%) | ||
| Postoperative abscess | 0/589 (0%) | 1/1180 (0.1%) | ||
| Pulmonary sepsis | 0/589 (0%) | 1/1180 (0.1%) | ||
| Pyelonephritis acute | 0/589 (0%) | 1/1180 (0.1%) | ||
| Rhinovirus infection | 0/589 (0%) | 1/1180 (0.1%) | ||
| Sinusitis | 0/589 (0%) | 1/1180 (0.1%) | ||
| Streptococcal sepsis | 0/589 (0%) | 1/1180 (0.1%) | ||
| Tooth abscess | 0/589 (0%) | 1/1180 (0.1%) | ||
| Bronchitis | 2/589 (0.3%) | 0/1180 (0%) | ||
| Abdominal infection | 1/589 (0.2%) | 0/1180 (0%) | ||
| Atypical pneumonia | 1/589 (0.2%) | 0/1180 (0%) | ||
| Cholecystitis infective | 1/589 (0.2%) | 0/1180 (0%) | ||
| Empyema | 1/589 (0.2%) | 0/1180 (0%) | ||
| Herpes zoster oticus | 1/589 (0.2%) | 0/1180 (0%) | ||
| Perineal abscess | 1/589 (0.2%) | 0/1180 (0%) | ||
| Vulval cellulitis | 1/354 (0.3%) | 0/749 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Fall | 5/589 (0.8%) | 2/1180 (0.2%) | ||
| Post procedural haematoma | 2/589 (0.3%) | 2/1180 (0.2%) | ||
| Procedural pain | 1/589 (0.2%) | 2/1180 (0.2%) | ||
| Tibia fracture | 1/589 (0.2%) | 2/1180 (0.2%) | ||
| Multiple injuries | 0/589 (0%) | 2/1180 (0.2%) | ||
| Road traffic accident | 1/589 (0.2%) | 1/1180 (0.1%) | ||
| Animal bite | 0/589 (0%) | 1/1180 (0.1%) | ||
| Craniocerebral injury | 0/589 (0%) | 1/1180 (0.1%) | ||
| Fibula fracture | 0/589 (0%) | 1/1180 (0.1%) | ||
| Humerus fracture | 0/589 (0%) | 1/1180 (0.1%) | ||
| Limb injury | 0/589 (0%) | 1/1180 (0.1%) | ||
| Post procedural contusion | 0/589 (0%) | 1/1180 (0.1%) | ||
| Post procedural hypotension | 0/589 (0%) | 1/1180 (0.1%) | ||
| Tendon rupture | 0/589 (0%) | 1/1180 (0.1%) | ||
| Thoracic vertebral fracture | 0/589 (0%) | 1/1180 (0.1%) | ||
| Wrist fracture | 0/589 (0%) | 1/1180 (0.1%) | ||
| Ankle fracture | 3/589 (0.5%) | 0/1180 (0%) | ||
| Femur fracture | 2/589 (0.3%) | 0/1180 (0%) | ||
| Anaemia postoperative | 1/589 (0.2%) | 0/1180 (0%) | ||
| Femoral neck fracture | 1/589 (0.2%) | 0/1180 (0%) | ||
| Post procedural complication | 1/589 (0.2%) | 0/1180 (0%) | ||
| Post procedural discomfort | 1/589 (0.2%) | 0/1180 (0%) | ||
| Rib fracture | 1/589 (0.2%) | 0/1180 (0%) | ||
| Snake bite | 1/589 (0.2%) | 0/1180 (0%) | ||
| Investigations | ||||
| SARS-CoV-2 test positive | 0/589 (0%) | 1/1180 (0.1%) | ||
| Serum ferritin increased | 0/589 (0%) | 1/1180 (0.1%) | ||
| Blood uric acid increased | 1/589 (0.2%) | 0/1180 (0%) | ||
| Transaminases increased | 1/589 (0.2%) | 0/1180 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Hyponatraemia | 0/589 (0%) | 2/1180 (0.2%) | ||
| Alkalosis hypochloraemic | 0/589 (0%) | 1/1180 (0.1%) | ||
| Alkalosis hypokalaemic | 0/589 (0%) | 1/1180 (0.1%) | ||
| Diabetic ketoacidosis | 0/589 (0%) | 1/1180 (0.1%) | ||
| Hyperkalaemia | 0/589 (0%) | 1/1180 (0.1%) | ||
| Hypoglycaemia | 0/589 (0%) | 1/1180 (0.1%) | ||
| Hypomagnesaemia | 0/589 (0%) | 1/1180 (0.1%) | ||
| Type 2 diabetes mellitus | 0/589 (0%) | 1/1180 (0.1%) | ||
| Dehydration | 1/589 (0.2%) | 0/1180 (0%) | ||
| Diabetes mellitus inadequate control | 1/589 (0.2%) | 0/1180 (0%) | ||
| Hypercalcaemia | 1/589 (0.2%) | 0/1180 (0%) | ||
| Hyperglycaemia | 1/589 (0.2%) | 0/1180 (0%) | ||
| Hypocalcaemia | 1/589 (0.2%) | 0/1180 (0%) | ||
| Hypokalaemia | 1/589 (0.2%) | 0/1180 (0%) | ||
| Obesity | 1/589 (0.2%) | 0/1180 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 0/589 (0%) | 4/1180 (0.3%) | ||
| Intervertebral disc degeneration | 0/589 (0%) | 2/1180 (0.2%) | ||
| Facet joint syndrome | 0/589 (0%) | 1/1180 (0.1%) | ||
| Flank pain | 0/589 (0%) | 1/1180 (0.1%) | ||
| Intervertebral disc displacement | 0/589 (0%) | 1/1180 (0.1%) | ||
| Intervertebral disc protrusion | 0/589 (0%) | 1/1180 (0.1%) | ||
| Lumbar spinal stenosis | 0/589 (0%) | 1/1180 (0.1%) | ||
| Mixed connective tissue disease | 0/589 (0%) | 1/1180 (0.1%) | ||
| Myositis | 0/589 (0%) | 1/1180 (0.1%) | ||
| Osteoarthritis | 0/589 (0%) | 1/1180 (0.1%) | ||
| Pain in extremity | 0/589 (0%) | 1/1180 (0.1%) | ||
| Cervical spinal stenosis | 2/589 (0.3%) | 0/1180 (0%) | ||
| Muscular weakness | 2/589 (0.3%) | 0/1180 (0%) | ||
| Chest wall haematoma | 1/589 (0.2%) | 0/1180 (0%) | ||
| Exostosis | 1/589 (0.2%) | 0/1180 (0%) | ||
| Systemic lupus erythematosus | 1/589 (0.2%) | 0/1180 (0%) | ||
| Tendonitis | 1/589 (0.2%) | 0/1180 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Squamous cell carcinoma of skin | 0/589 (0%) | 3/1180 (0.3%) | ||
| Basal cell carcinoma | 0/589 (0%) | 2/1180 (0.2%) | ||
| Prostate cancer | 0/235 (0%) | 2/431 (0.5%) | ||
| Acoustic neuroma | 0/589 (0%) | 1/1180 (0.1%) | ||
| Adenocarcinoma pancreas | 0/589 (0%) | 1/1180 (0.1%) | ||
| Basosquamous carcinoma | 0/589 (0%) | 1/1180 (0.1%) | ||
| Bile duct cancer | 0/589 (0%) | 1/1180 (0.1%) | ||
| Bladder transitional cell carcinoma | 0/589 (0%) | 1/1180 (0.1%) | ||
| Bowen's disease | 0/589 (0%) | 1/1180 (0.1%) | ||
| Brain neoplasm benign | 0/589 (0%) | 1/1180 (0.1%) | ||
| Endometrial neoplasm | 0/354 (0%) | 1/749 (0.1%) | ||
| Hepatic cancer | 0/589 (0%) | 1/1180 (0.1%) | ||
| Intraductal proliferative breast lesion | 0/589 (0%) | 1/1180 (0.1%) | ||
| Invasive ductal breast carcinoma | 0/589 (0%) | 1/1180 (0.1%) | ||
| Leiomyosarcoma | 0/589 (0%) | 1/1180 (0.1%) | ||
| Malignant melanoma of eyelid | 0/589 (0%) | 1/1180 (0.1%) | ||
| Non-small cell lung cancer | 0/589 (0%) | 1/1180 (0.1%) | ||
| Pancreatic neuroendocrine tumour | 0/589 (0%) | 1/1180 (0.1%) | ||
| Papillary thyroid cancer | 0/589 (0%) | 1/1180 (0.1%) | ||
| Pituitary tumour benign | 0/589 (0%) | 1/1180 (0.1%) | ||
| Plasma cell myeloma | 0/589 (0%) | 1/1180 (0.1%) | ||
| Renal cancer | 0/589 (0%) | 1/1180 (0.1%) | ||
| Squamous cell carcinoma | 0/589 (0%) | 1/1180 (0.1%) | ||
| Hepatocellular carcinoma | 2/589 (0.3%) | 0/1180 (0%) | ||
| Pancreatic carcinoma | 2/589 (0.3%) | 0/1180 (0%) | ||
| Brain neoplasm | 1/589 (0.2%) | 0/1180 (0%) | ||
| Endometrial cancer | 1/354 (0.3%) | 0/749 (0%) | ||
| Malignant melanoma | 1/589 (0.2%) | 0/1180 (0%) | ||
| Tumour of ampulla of Vater | 1/589 (0.2%) | 0/1180 (0%) | ||
| Nervous system disorders | ||||
| Cerebrovascular accident | 2/589 (0.3%) | 3/1180 (0.3%) | ||
| Transient ischaemic attack | 1/589 (0.2%) | 3/1180 (0.3%) | ||
| Paraesthesia | 0/589 (0%) | 2/1180 (0.2%) | ||
| Dizziness | 1/589 (0.2%) | 1/1180 (0.1%) | ||
| Loss of consciousness | 1/589 (0.2%) | 1/1180 (0.1%) | ||
| Brain stem infarction | 0/589 (0%) | 1/1180 (0.1%) | ||
| Cervical radiculopathy | 0/589 (0%) | 1/1180 (0.1%) | ||
| Facial paralysis | 0/589 (0%) | 1/1180 (0.1%) | ||
| Headache | 0/589 (0%) | 1/1180 (0.1%) | ||
| Radial nerve palsy | 0/589 (0%) | 1/1180 (0.1%) | ||
| Coma | 1/589 (0.2%) | 0/1180 (0%) | ||
| Hypersomnia | 1/589 (0.2%) | 0/1180 (0%) | ||
| Lethargy | 1/589 (0.2%) | 0/1180 (0%) | ||
| Syncope | 1/589 (0.2%) | 0/1180 (0%) | ||
| Pregnancy, puerperium and perinatal conditions | ||||
| Ruptured ectopic pregnancy | 1/354 (0.3%) | 0/749 (0%) | ||
| Product Issues | ||||
| Device dislocation | 0/589 (0%) | 1/1180 (0.1%) | ||
| Psychiatric disorders | ||||
| Depression | 1/589 (0.2%) | 2/1180 (0.2%) | ||
| Suicidal ideation | 1/589 (0.2%) | 1/1180 (0.1%) | ||
| Mental status changes | 1/589 (0.2%) | 0/1180 (0%) | ||
| Psychiatric decompensation | 1/589 (0.2%) | 0/1180 (0%) | ||
| Suicide attempt | 1/589 (0.2%) | 0/1180 (0%) | ||
| Renal and urinary disorders | ||||
| Nephrolithiasis | 0/589 (0%) | 4/1180 (0.3%) | ||
| Acute kidney injury | 1/589 (0.2%) | 3/1180 (0.3%) | ||
| Haematuria | 0/589 (0%) | 2/1180 (0.2%) | ||
| Renal colic | 0/589 (0%) | 2/1180 (0.2%) | ||
| Ureterolithiasis | 0/589 (0%) | 1/1180 (0.1%) | ||
| Urinary retention | 0/589 (0%) | 1/1180 (0.1%) | ||
| Urinary tract obstruction | 0/589 (0%) | 1/1180 (0.1%) | ||
| Reproductive system and breast disorders | ||||
| Benign prostatic hyperplasia | 1/235 (0.4%) | 1/431 (0.2%) | ||
| Metrorrhagia | 0/354 (0%) | 1/749 (0.1%) | ||
| Polycystic ovaries | 0/354 (0%) | 1/749 (0.1%) | ||
| Endometrial hyperplasia | 1/354 (0.3%) | 0/749 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Pulmonary embolism | 0/589 (0%) | 3/1180 (0.3%) | ||
| Asthma | 0/589 (0%) | 2/1180 (0.2%) | ||
| Pleural effusion | 1/589 (0.2%) | 1/1180 (0.1%) | ||
| Acute respiratory distress syndrome | 0/589 (0%) | 1/1180 (0.1%) | ||
| Dyspnoea | 0/589 (0%) | 1/1180 (0.1%) | ||
| Interstitial lung disease | 0/589 (0%) | 1/1180 (0.1%) | ||
| Respiratory distress | 0/589 (0%) | 1/1180 (0.1%) | ||
| Sleep apnoea syndrome | 0/589 (0%) | 1/1180 (0.1%) | ||
| Acute respiratory failure | 1/589 (0.2%) | 0/1180 (0%) | ||
| Chronic obstructive pulmonary disease | 1/589 (0.2%) | 0/1180 (0%) | ||
| Haemothorax | 1/589 (0.2%) | 0/1180 (0%) | ||
| Respiratory failure | 1/589 (0.2%) | 0/1180 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Rash erythematous | 1/589 (0.2%) | 1/1180 (0.1%) | ||
| Diabetic foot | 0/589 (0%) | 1/1180 (0.1%) | ||
| Pruritus | 0/589 (0%) | 1/1180 (0.1%) | ||
| Vascular disorders | ||||
| Aortic stenosis | 1/589 (0.2%) | 1/1180 (0.1%) | ||
| Deep vein thrombosis | 0/589 (0%) | 1/1180 (0.1%) | ||
| Hypertension | 0/589 (0%) | 1/1180 (0.1%) | ||
| Phlebolith | 0/589 (0%) | 1/1180 (0.1%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Placebo | Cenicriviroc 150 mg | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 218/589 (37%) | 425/1180 (36%) | ||
| Gastrointestinal disorders | ||||
| Nausea | 39/589 (6.6%) | 104/1180 (8.8%) | ||
| Diarrhoea | 56/589 (9.5%) | 92/1180 (7.8%) | ||
| Abdominal pain upper | 26/589 (4.4%) | 64/1180 (5.4%) | ||
| Abdominal pain | 30/589 (5.1%) | 56/1180 (4.7%) | ||
| General disorders | ||||
| Fatigue | 33/589 (5.6%) | 74/1180 (6.3%) | ||
| Infections and infestations | ||||
| Urinary tract infection | 33/589 (5.6%) | 57/1180 (4.8%) | ||
| Upper respiratory tract infection | 39/589 (6.6%) | 41/1180 (3.5%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 35/589 (5.9%) | 68/1180 (5.8%) | ||
| Back pain | 36/589 (6.1%) | 54/1180 (4.6%) | ||
| Nervous system disorders | ||||
| Headache | 30/589 (5.1%) | 64/1180 (5.4%) | ||
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.
Results Point of Contact
| Name/Title | Therapeutic Area, Head |
|---|---|
| Organization | Allergan |
| Phone | 714-246-4500 |
| clinicaltrials@allergan.com |
Responsible Party:
Tobira Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT03028740
Other Study ID Numbers:
- 3152-301-002
- 2016-004566-26
- 1001
First Posted:
Jan 23, 2017
Last Update Posted:
Mar 10, 2022
Last Verified:
Nov 1, 2021