Emricasan, a Caspase Inhibitor, for Treatment of Subjects With Decompensated NASH Cirrhosis (ENCORE-LF)
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| ClinicalTrials.gov Identifier: NCT03205345 |
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Recruitment Status : Unknown
Verified March 2019 by Conatus Pharmaceuticals Inc..
Recruitment status was: Active, not recruiting
First Posted : July 2, 2017
Last Update Posted : March 19, 2019
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Sponsor:
Conatus Pharmaceuticals Inc.
Information provided by (Responsible Party):
Conatus Pharmaceuticals Inc.
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Brief Summary:
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Decompensated Cirrhosis | Drug: Emricasan (25 mg) Drug: Emricasan (5 mg) Drug: Placebo | Phase 2 |
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:
- Screening period of up to 4 weeks
- Randomized, double-blind treatment period of at least 48 weeks
- A follow-up visit 2 weeks after completion of study drug treatment
The duration of each subject's participation will be at least 54 weeks for those completing the entire study.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 210 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Investigator, Outcomes Assessor) |
| Masking Description: | 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. |
| Primary Purpose: | Treatment |
| Official Title: | A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Emricasan, an Oral Caspase Inhibitor, in Subjects With Decompensated Non-Alcoholic Steatohepatitis (NASH) Cirrhosis |
| Actual Study Start Date : | June 28, 2017 |
| Estimated Primary Completion Date : | August 2019 |
| Estimated Study Completion Date : | August 2019 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
North American Indian childhood cirrhosis
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Emricasan (25 mg)
Emricasan 25 mg
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Drug: Emricasan (25 mg)
25 mg emricasan
Other Name: IDN-6556 |
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Active Comparator: Emricasan (5 mg)
Emricasan 5mg
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Drug: Emricasan (5 mg)
5 mg emricasan
Other Name: IDN-6556 |
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Placebo Comparator: Placebo
Matching placebo
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Drug: Placebo
Matching Placebo
Other Name: Matching placebo |
Primary Outcome Measures :
- Comparison of the effect of emricasan on improving event-free survival relative to placebo, based on a composite clinical endpoint [ Time Frame: Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) ]
Secondary Outcome Measures :
- Improvement in MELD score [ Time Frame: Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) ]The effect of emricasan on improving MELD score relative to placebo
- Improvement in Child-Pugh scores [ Time Frame: Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) ]The effect of emricasan on improving the Child-Pugh score relative to placebo
- Reduction of the proportion of subjects with MELD score progression [ Time Frame: Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) ]The effect of emricasan on reducing the proportion of patients with MELD score progression (≥4 point increase at any study visit) relative to placebo
- Decrease in new decompensation events [ Time Frame: Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) ]The effect of emricasan on decreasing new decompensation events relative to placebo
- Decrease in liver transplantation rates [ Time Frame: Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) ]The effect of emricasan on decreasing liver transplantation rates (in association with MELD score ≥25) relative to placebo
- Decrease in all-cause and liver specific mortality [ Time Frame: Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) ]The effect of emricasan on decreasing all-cause and liver specific mortality relative to placebo
- Improvement in health-related quality of life (QOL) as measured by Short Form-36 [ Time Frame: 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) [ Time Frame: Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) ]
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Key Inclusion Criteria:
- Male or female subjects 18 years or older, able to provide written informed consent and able to understand and willing to comply with the requirements of the study.
- Cirrhosis due to NASH with exclusion of other causes of cirrhosis (e.g. chronic viral hepatitis, alcoholic liver disease, etc.)
- At least one of the following: a) history of variceal hemorrhage (more than 3 months prior to day 1) documented on endoscopy and requiring blood transfusion, b) history of at least moderate ascites (on physical exam or imaging) currently treated with diuretics.
- MELD score ≥12 and ≤20 during screening
- Albumin ≥2.5 g/dL during screening
- Serum creatinine ≤1.5 mg/dL during screening
Key Exclusion Criteria:
- Evidence of severe decompensation
- Non-cirrhotic portal hypertension
- Child-Pugh score ≥10
- Current use of anticoagulants that affect prothrombin time or international normalized ratio
- ALT >3 times upper limit of normal (ULN) or AST >5 times ULN during screening
- Initiation or discontinuation of non-selective beta blockers within 1 month of screening
- Transjugular intrahepatic portosystemic shunt or other porto-systemic bypass procedure within 1 year of screening or previously requiring revision
- Alpha-fetoprotein >50 ng/mL in the last year
- History of hepatocellular carcinoma (HCC) or evidence of HCC
- History of malignancies other than HCC, unless successfully treated with curative intent and believed to be cured
- Prior liver transplant
- Uncontrolled diabetes mellitus (HbA1c >9%)
- Change in diabetes medications or vitamin E within 3 months of screening
- Restrictive bariatric surgery or bariatric device within 1 year of screening or prior malabsorptive bariatric surgery
- Symptoms of biliary colic unless resolved following cholecystectomy
- History of significant alcohol consumption within the past 5 years
- Current use of medications that are considered inhibitors of organic anion transporting polypeptide OATP1B1 and OATP1B3 transporters
- Prolongation of screening (pre-treatment) QTcF interval of >500 msecs, or history or presence of clinically concerning cardiac arrhythmias
- Significant systemic or major illness other than liver disease
- Human immunodeficiency virus infection
- Use of alcohol, controlled substances (including inhaled or injected drugs), or non-prescribed use of prescription drugs within 1 year of screening to the point of interfering with the subject's ability to comply with study procedures and study drug administration in the investigator's judgement
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03205345
Locations
Show 76 study locations
Sponsors and Collaborators
Conatus Pharmaceuticals Inc.
Investigators
| Study Director: | Jean L Chan, MD | Conatus Pharmaceuticals |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Conatus Pharmaceuticals Inc. |
| ClinicalTrials.gov Identifier: | NCT03205345 |
| Other Study ID Numbers: |
IDN-6556-17 |
| First Posted: | July 2, 2017 Key Record Dates |
| Last Update Posted: | March 19, 2019 |
| Last Verified: | March 2019 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Conatus Pharmaceuticals Inc.:
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Cirrhosis NASH Cirrhosis Decompensated NASH cirrhosis Cirrhosis, Liver Non-Alcoholic Fatty Liver Disease |
Additional relevant MeSH terms:
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Liver Cirrhosis Fibrosis Pathologic Processes Liver Diseases Digestive System Diseases |