Companion Protocol for Methacetin Breath Test (MBT) in Conatus Protocol IDN-6556-14

Meridian Bioscience

Status: Completed

Conditions: Portal Hypertension; Cirrhosis; NASH - Nonalcoholic Steatohepatitis

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

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT03439189

CON-EX-0616

Details and patient eligibility

About

To validate the ability of the Methacetin Breath Test (MBT) to detect clinically significant portal hypertension (CSPH)/severe portal hypertension (SPH) defined as hepatic venous pressure gradient (HVPG) ≥ 10 mmHg and HVPG ≥ 12 mmHg respectively, in patients with non-alcoholic steatohepatitis (NASH) during the course of treatment with Conatus's investigational product emricasan/placebo.

Full description

This study is a companion protocol that will use the data generated by Conatus' study of emricasan under protocol IDN-6556-14 (NCT02960204).The IDN-6556-14 study is a Phase 2, multicenter, double-blind, randomized, placebo-controlled trial in subjects with non-alcoholic steatohepatitis (NASH) cirrhosis and severe portal hypertension.

As one of the Conatus' study exploratory objectives, this companion protocol is designed to assess whether emricasan compared to placebo improves liver metabolic function at Weeks 24 and 48 as assessed by the methacetin breath test (at select sites), if relevant.

Enrollment: 343 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. Compensated cirrhosis OR Decompensated cirrhosis with no more than 1 prior significant decompensating event.
4. Severe portal hypertension defined as HVPG ≥12 mmHg
5. Subjects who are on NSBB, nitrates, diuretics, lactulose, rifaximin, or statins must be on a stable dose for at least 3 months prior to Day 1
6. Willingness to utilize effective contraception (for both males and females of childbearing potential) from Screening to 4 weeks after the last dose of study drug

Exclusion criteria

1. Evidence of severe decompensation
2. Severe hepatic impairment defined as a Child-Pugh score ≥10
3. ALT >3 times upper limit of normal (ULN) or AST >5 times ULN during screening
4. Estimated creatinine clearance <30 mL/min
5. Prior transjugular intrahepatic portosystemic shunt or other porto-systemic bypass procedure
6. Known portal vein thrombosis
7. Symptoms of biliary colic, e.g. due to symptomatic gallstones, within the last 6 months, unless resolved following cholecystectomy, other definitive treatment (e.g. sphincterotomy), or medical management (e.g. ursodeoxycholic acid)
8. Current use of medications that are considered inhibitors of OATP1B1 and OATP1B3 transporters
9. Alpha-fetoprotein >50 ng/mL
10. History or presence of clinically concerning cardiac arrhythmias, or prolongation of screening (pre-treatment) QTcF interval of >500 msec
11. History of or active malignancies, other than those successfully treated with curative intent and believed to be cured
12. Prior liver transplant
13. Change in diabetes medications or vitamin E within 3 months of screening
14. Uncontrolled diabetes mellitus (HbA1c >9%) within 3 months of screening
15. Significant systemic or major illness other than liver disease
16. HIV infection
17. Use of controlled substances (including inhaled or injected drugs) or non-prescribed use of prescription drugs within 1 year of screening
18. If female: planned or known pregnancy, positive urine or serum pregnancy test, or lactating/breastfeeding
19. Previous treatment with emricasan or active investigational medication (except methacetin) in a clinical trial within 3 months prior to Day 1

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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343 participants in 4 patient groups, including a placebo group

Emricasan 5mg

Experimental group

Description:

Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (5 mg) twice a day. The MBT will be performed at screening, at week 24/week 48/at early termination.

Treatment:

Drug: Emricasan

Combination Product: Methacetin Breath Test

Emricasan 25mg

Experimental group

Description:

Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (25 mg) twice a day. The MBT will be performed at screening, at week 24/ week 48/ at early termination.

Treatment:

Drug: Emricasan

Combination Product: Methacetin Breath Test

Emricasan 50mg

Experimental group

Description:

Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (50 mg) twice a day. The MBT will be performed at screening, at week 24/ week 48/ at early termination.

Treatment:

Drug: Emricasan

Combination Product: Methacetin Breath Test

Placebo

Placebo Comparator group

Description:

Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with a matching placebo twice a day. The MBT will be performed at screening, at week 24/week 48/at early termination.

Treatment:

Drug: Placebo oral capsule

Combination Product: Methacetin Breath Test