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

NCT03439189 | Completed Results

• 1 other identifier: CON-EX-0616
• Study Type: interventional
• Target: 343
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

NASH - Nonalcoholic Steatohepatitis; Cirrhosis; Portal Hypertension

Outcome Measures

Primary Outcomes (1)

• Number of Subjects With Matched Clinically Significant Portal Hypertension Based on Hepatic Venous Pressure Gradient (HVPG) and Methacetin Breath Test (MBT)

  Binary diagnosis of clinically significant portal hypertension (CSPH) as determined by HVPG, defined as HVPG ≥ 10mmHg and by the MBT derived from an algorithm developed under other Exalenz clinical studies

  1 hour for MBT related to assessment of this diagnostic primary outcome assesses during screening

Secondary Outcomes (1)

• Number of Matched Subjects With Significant Portal Hypertension (Defined as HVPG>=12mmHg) Based on HVPG and MBT

  1 hour for MBT for assessment of this diagnostic secondary outcome assessed during screening

Study Arms (4)

Emricasan 5mg

EXPERIMENTAL

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.

Combination Product: Methacetin Breath Test; Drug: Emricasan

Emricasan 25mg

EXPERIMENTAL

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.

Combination Product: Methacetin Breath Test; Drug: Emricasan

Emricasan 50mg

EXPERIMENTAL

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.

Combination Product: Methacetin Breath Test; Drug: Emricasan

Placebo

PLACEBO COMPARATOR

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.

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

Interventions

Methacetin Breath Test COMBINATION_PRODUCT

A breath analyzer will be used to measure changes in carbon-12 to carbon-13 ratio as a result of metabolism of the Methacetin substrate before and after treatment.

Emricasan 25mg; Emricasan 50mg; Emricasan 5mg; Placebo

Emricasan DRUG

Investigational drug for NASH treatment in Main Conatus protocol

Emricasan 25mg; Emricasan 50mg; Emricasan 5mg

Placebo oral capsule DRUG

Placebo versus emricasan in Conatus NASH treatment trial

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Compensated cirrhosis OR Decompensated cirrhosis with no more than 1 prior significant decompensating event.
• Severe portal hypertension defined as HVPG ≥12 mmHg
• 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
• 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

You may not qualify if:

• Evidence of severe decompensation
• Severe hepatic impairment defined as a Child-Pugh score ≥10
• ALT \>3 times upper limit of normal (ULN) or AST \>5 times ULN during screening
• Estimated creatinine clearance \<30 mL/min
• Prior transjugular intrahepatic portosystemic shunt or other porto-systemic bypass procedure
• Known portal vein thrombosis
• 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)
• Current use of medications that are considered inhibitors of OATP1B1 and OATP1B3 transporters
• Alpha-fetoprotein \>50 ng/mL
• History or presence of clinically concerning cardiac arrhythmias, or prolongation of screening (pre-treatment) QTcF interval of \>500 msec
• History of or active malignancies, other than those successfully treated with curative intent and believed to be cured
• Prior liver transplant
• Change in diabetes medications or vitamin E within 3 months of screening
• Uncontrolled diabetes mellitus (HbA1c \>9%) within 3 months of screening
• Significant systemic or major illness other than liver disease

Sponsors & Collaborators

• Meridian Bioscience, Inc.: lead
• Conatus Pharmaceuticals Inc.: collaborator

Study Sites (1)

Hopital Beaujon

Clichy, 92118, France

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Fibrosis; Hypertension, Portal

Interventions

3-(2-(2-tert-butylphenylaminooxalyl)aminopropionylamino)-4-oxo-5-(2,3,5,6-tetrafluorophenoxy)pentanoic acid

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Clinical trial manager
• Organization: Exalenz Bioscience

avrahamh@exalenz.com

00 972 546605412

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The collaborator is responsible for the masking process.
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The population performing the MBT at weeks 24 and 48 will have approximately an equal number of subjects from each of the 4 parallel treatment arms (5 mg, 25 mg, 50 mg or placebo).

Study Record Dates

• First Submitted: January 29, 2018
• First Posted: February 20, 2018
• Study Start: August 28, 2016
• Primary Completion: April 8, 2019
• Study Completion: May 13, 2019
• Last Updated: December 20, 2022
• Results First Posted: September 4, 2020

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)