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

Meridian Bioscience

Status: Terminated

Conditions: Decompensated Cirrhosis

Treatments: Combination Product: Methacetin Breath Test; Drug: Emricasan; Drug: Placebo oral capsule

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT03462576

CON-EX-0217

Details and patient eligibility

About

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.

Full 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) ].

Enrollment: 199 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. 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.
2. Cirrhosis due to NASH with exclusion of other causes of cirrhosis (e.g. chronic viral hepatitis, alcoholic liver disease, etc.)
3. 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.
4. MELD score ≥12 and ≤20 during screening
5. Albumin ≥2.5 g/dL during screening
6. Serum creatinine ≤1.5 mg/dL during screening

Exclusion criteria

1. Evidence of severe decompensation
2. Non-cirrhotic portal hypertension
3. Child-Pugh score ≥10
4. Current use of anticoagulants that affect prothrombin time or international normalized ratio
5. ALT >3 times upper limit of normal (ULN) or AST >5 times ULN during screening
6. Initiation or discontinuation of non-selective beta blockers within 1 month of screening
7. Transjugular intrahepatic portosystemic shunt or other porto-systemic bypass procedure within 1 year of screening or previously requiring revision
8. Alpha-fetoprotein >50 ng/mL in the last year
9. History of hepatocellular carcinoma (HCC) or evidence of HCC
10. History of malignancies other than HCC, unless successfully treated with curative intent and believed to be cured
11. Prior liver transplant
12. Uncontrolled diabetes mellitus (HbA1c >9%)
13. Change in diabetes medications or vitamin E within 3 months of screening
14. Restrictive bariatric surgery or bariatric device within 1 year of screening or prior malabsorptive bariatric surgery
15. Symptoms of biliary colic unless resolved following cholecystectomy
16. History of significant alcohol consumption within the past 5 years
17. Current use of medications that are considered inhibitors of organic anion transporting polypeptide OATP1B1 and OATP1B3 transporters
18. Prolongation of screening (pre-treatment) QTcF interval of >500 msecs, or history or presence of clinically concerning cardiac arrhythmias
19. Significant systemic or major illness other than liver disease
20. Human immunodeficiency virus infection
21. 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

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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199 participants in 3 patient groups, including a placebo group

Emricasan 25mg

Experimental group

Description:

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.

Treatment:

Drug: Emricasan

Combination Product: Methacetin Breath Test

Emricasan 5mg

Experimental group

Description:

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.

Treatment:

Drug: Emricasan

Combination Product: Methacetin Breath Test

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo oral capsule

Combination Product: Methacetin Breath Test