Companion Protocol for Methacetin Breath Test (MBT) in Conatus Protocol IDN-6556-17

Terminated

Conditions: Decompensated Cirrhosis

Interventions: Combination Product: Methacetin Breath Test
Drug: Emricasan
Drug: Placebo oral capsule

Registration Number: NCT03462576

Lead Sponsor: Meridian Bioscience, Inc.

Brief Summary: This study is a companion protocol that will use the data generated by Conatus' study of emricasan under protocol IDN-6556-17.The IDN-6556-17 study is a Phase 2, multicenter, double-blind, placebo-controlled trial of Emricasan in subjects with decompensated non-alcoholic steatohepatitis (NASH) cirrhosis.

Detailed Description: The protocol is intended to validate the ability of the MBT to predict deterioration by 48 weeks for all subjects, and at later time points for those followed longer, for subjects with decompensated NASH cirrhosis in the placebo treatment arm of Conatus' study IDN-6556-17.

As one of the Conatus' study secondary objectives, this companion protocol is designed to assess improvement in liver metabolic function as measured by Methacetin Breath Test (MBT) \[ Time Frame: Baseline - Final Treatment Visit (at least 48 weeks to a max of 120 weeks) \].

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 199

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

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Emricasan 25mg	Methacetin Breath Test	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.
Emricasan 25mg	Emricasan	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.
Emricasan 5mg	Methacetin Breath Test	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.
Emricasan 5mg	Emricasan	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.
Placebo	Methacetin Breath Test	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.
Placebo	Placebo oral capsule	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.

Primary Outcome Measures

Name	Time	Method
Number of Subjects Experiencing a High Risk Event Based on a 5.5%/Hour Cut-off	1 hour for MBT for assessment of this diagnostic outcome assessed during screening	Binary diagnosis of subjects that are at high risk to develop a deterioration event as determined by the Methacetin Breath Test (MBT) derived from an algorithm developed under other Exalenz clinical studies using a pre-designed cutoff of Percentage Dose Recovery (PDR) peak of \< 5.5%/hour. The data was collected and analyzed agnostic to the intervention.

Secondary Outcome Measures

Name	Time	Method
Number of Subjects Experiencing a High Risk Event Based on a 7.5 %/Hour Cut-off	1 hour for MBT for assessment of this diagnostic outcome assessed during screening	Binary diagnosis of subjects that are at high risk to develop a deterioration event as determined by the Methacetin Breath Test (MBT) derived from an algorithm developed under other Exalenz clinical studies using a pre-designed cutoff of Percentage Dose Recovery (PDR) peak of \< 7.5%/hour.The data was collected and analyzed agnostic to the intervention.