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This is a multicenter, double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of emricasan in improving event-free survival based on a composite clinical endpoint (where all-cause mortality, new decompensation events, and MELD score progression are events) in subjects with decompensated NASH cirrhosis.
The study treatment duration will be at least 48 weeks with study visits every 4 weeks up to Week 48 and every 8 weeks after Week 48. All subjects will continue treatment until the last subject in the study reaches 48 weeks in the study. At least 30% of subjects randomized should have baseline MELD score ≥15 and ≤20.
For each subject, the study will consist of:
The duration of each subject's participation will be at least 54 weeks for those completing the entire study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Emricasan (25 mg) | Active Comparator | Emricasan 25 mg |
|
| Emricasan (5 mg) | Active Comparator | Emricasan 5mg |
|
| Placebo | Placebo Comparator | Matching placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Emricasan (25 mg) | Drug | 25 mg emricasan |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Comparison of the effect of emricasan on improving event-free survival relative to placebo, based on a composite clinical endpoint | Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Improvement in MELD score | The effect of emricasan on improving MELD score relative to placebo | Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) |
| Improvement in Child-Pugh scores |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jean L Chan, MD | Conatus Pharmaceuticals Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Institute for Liver Health | Chandler | Arizona | 85224 | United States | ||
| St. Joseph's Hospital & Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33038432 | Derived | Frenette C, Kayali Z, Mena E, Mantry PS, Lucas KJ, Neff G, Rodriguez M, Thuluvath PJ, Weinberg E, Bhandari BR, Robinson J, Wedick N, Chan JL, Hagerty DT, Kowdley KV; IDN-6556-17 Study Investigators. Emricasan to prevent new decompensation in patients with NASH-related decompensated cirrhosis. J Hepatol. 2021 Feb;74(2):274-282. doi: 10.1016/j.jhep.2020.09.029. Epub 2020 Oct 8. |
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Study drug will be double-blind with matching placebo. Emricasan at 25 mg or 5 mg or matching placebo will be administered orally twice a day.
| Emricasan (5 mg) | Drug | 5 mg emricasan |
|
|
| Placebo | Drug | Matching Placebo |
|
|
The effect of emricasan on improving the Child-Pugh score relative to placebo
| Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) |
| Reduction of the proportion of subjects with MELD score progression | The effect of emricasan on reducing the proportion of patients with MELD score progression (≥4 point increase at any study visit) relative to placebo | Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) |
| Decrease in new decompensation events | The effect of emricasan on decreasing new decompensation events relative to placebo | Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) |
| Decrease in liver transplantation rates | The effect of emricasan on decreasing liver transplantation rates (in association with MELD score ≥25) relative to placebo | Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) |
| Decrease in all-cause and liver specific mortality | The effect of emricasan on decreasing all-cause and liver specific mortality relative to placebo | Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) |
| Improvement in health-related quality of life (QOL) as measured by Short Form-36 | Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) |
| Improvement in liver metabolic function as measured by Methacetin Breath Test (MBT) | Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) |
| Phoenix |
| Arizona |
| 85013 |
| United States |
| Mayo Clinic Arizona | Phoenix | Arizona | 85054 | United States |
| University of Arizona Liver Research Institute | Tucson | Arizona | 85747 | United States |
| University of California, San Francisco-Fresno | Fresno | California | 93701 | United States |
| Cedars Sinai Medical Center | Los Angeles | California | 90048 | United States |
| UCLA Pfleger Liver Institute | Los Angeles | California | 90095 | United States |
| California Liver Research Institute | Pasadena | California | 91105 | United States |
| Stanford University | Redwood City | California | 94063 | United States |
| Inland Empire Liver Foundation | Rialto | California | 92377 | United States |
| UC Davis GI/Hepatology Clinical Trials Unit | Sacramento | California | 95817 | United States |
| Scripps Clinic - Torrey Pines | San Diego | California | 92037 | United States |
| California Pacific Medical Center | San Francisco | California | 94115 | United States |
| University of California San Francisco | San Francisco | California | 94143 | United States |
| University of Colorado Denver | Aurora | Colorado | 80045 | United States |
| Peak Enterology Associates | Colorado Springs | Colorado | 80907 | United States |
| West Haven VA Medical Center | West Haven | Connecticut | 06516 | United States |
| UF Hepatology Research at CTRB | Gainesville | Florida | 32610 | United States |
| Mayo Clinic | Jacksonville | Florida | 32224 | United States |
| Florida Research Institute | Lakewood Rch | Florida | 34211 | United States |
| Schiff Center for Liver Disease/University of Miami | Miami | Florida | 33136 | United States |
| Florida Hospital Transplant Institute | Orlando | Florida | 32804 | United States |
| IMIC Inc. | Palmetto Bay | Florida | 33157 | United States |
| Tampa General Hospital | Tampa | Florida | 33606 | United States |
| Piedmont Transplant Institute | Atlanta | Georgia | 30309 | United States |
| Gastrointestinal Specialists of Georgia | Marietta | Georgia | 30060 | United States |
| Northwestern University | Chicago | Illinois | 60611 | United States |
| Rush University Medical Center | Chicago | Illinois | 60612 | United States |
| Aquiant Research | Albany | Indiana | 47150 | United States |
| Indiana University | Indianapolis | Indiana | 46202 | United States |
| University of Iowa Hospitals and Clinics/ Internal Medicine | Iowa City | Iowa | 52242 | United States |
| Delta Research Partners | Bastrop | Louisiana | 71220 | United States |
| Ochsner Clinic Foundation | New Orleans | Louisiana | 70121 | United States |
| Mercy Medical Center | Baltimore | Maryland | 21202 | United States |
| Walter Reed National Military Medical Center (WRNMMC) | Bethesda | Maryland | 20889 | United States |
| Digestive Disease Associates, PA | Catonsville | Maryland | 21228 | United States |
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| Beth Israel Deaconess Medical Center | Boston | Massachusetts | 02215 | United States |
| Henry Ford Health System | Detroit | Michigan | 48202 | United States |
| Mayo Clinic | Rochester | Minnesota | 55901 | United States |
| University of Mississippi Medical Center, Division of Digestive Diseases | Jackson | Mississippi | 39216 | United States |
| Kansas City Research Institute | Kansas City | Missouri | 64131 | United States |
| Rutgers New Jersey Medical School | Newark | New Jersey | 07103 | United States |
| Northwell Health Inc., Sandra Atlas Bass Center for Liver Diseases. | Manhasset | New York | 11030 | United States |
| NYU Medical Center | New York | New York | 10016 | United States |
| Weill Cornell Medical College | New York | New York | 10021 | United States |
| Columbia University Medical Center - Center for Liver Disease and Transplantation | New York | New York | 10032 | United States |
| University of Rochester Medical Center | Rochester | New York | 14642 | United States |
| Carolinas Healthcare System, Center for Liver Disease | Charlotte | North Carolina | 28204 | United States |
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| Diabetes & Endocrinology Consultants, PC | Morehead City | North Carolina | 28557 | United States |
| UC Health/ UCPC LLC | Cincinnati | Ohio | 45267 | United States |
| Options Health Research, LLC | Tulsa | Oklahoma | 74104 | United States |
| Hospital of the University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| Medical University of South Carolina | Charleston | South Carolina | 29425 | United States |
| GHS Gastroenterology and Liver Center | Greenville | South Carolina | 29605 | United States |
| ClinSearch, LLC | Chattanooga | Tennessee | 37421 | United States |
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232 | United States |
| Texas Clinical Research Institute | Arlington | Texas | 76012 | United States |
| Methodist Health System Clinical Research Institute | Dallas | Texas | 75203 | United States |
| University of Texas Southwestern Medical Center | Dallas | Texas | 75390 | United States |
| Baylor Scott & White Research Institute | Fort Worth | Texas | 76104 | United States |
| Baylor College of Medicine - Advanced Liver Therapies | Houston | Texas | 77030 | United States |
| Liver Associates of Texas, P.A. | Houston | Texas | 77030 | United States |
| American Research Corporation at the Texas Liver Institue | San Antonio | Texas | 78215 | United States |
| Methodist Specialty & Transplant Hospital | San Antonio | Texas | 78229 | United States |
| San Antonio Military Medical Center | San Antonio | Texas | 78234 | United States |
| University of Utah | Salt Lake City | Utah | 84132 | United States |
| University of Virginia | Charlottesville | Virginia | 22908 | United States |
| Emeritas Research Group LLC | Leesburg | Virginia | 20176 | United States |
| Banner University Medical Center - Phoenix Transplant Institute | Newport News | Virginia | 23602 | United States |
| Bon Secours Liver Institute of Virginia | Richmond | Virginia | 23226 | United States |
| Virginia Commonwealth University | Richmond | Virginia | 23298 | United States |
| Swedish Organ Transplant and Liver Center | Seattle | Washington | 98104 | United States |
| University of Washington Harborview Medical Center | Seattle | Washington | 98104 | United States |
| University of Washington | Seattle | Washington | 98195 | United States |
| ID | Term |
|---|---|
| D005355 | Fibrosis |
| D008103 | Liver Cirrhosis |
| D065626 | Non-alcoholic Fatty Liver Disease |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D005234 | Fatty Liver |
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| ID | Term |
|---|---|
| C487112 | 3-(2-(2-tert-butylphenylaminooxalyl)aminopropionylamino)-4-oxo-5-(2,3,5,6-tetrafluorophenoxy)pentanoic acid |
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