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

Primary Purpose

NASH - Nonalcoholic Steatohepatitis, Cirrhosis, Portal Hypertension

Status

Completed

Phase

Locations

France

Study Type

Interventional

Intervention

Methacetin Breath Test

Emricasan

Placebo oral capsule

About this trial

This is an interventional diagnostic trial for NASH - Nonalcoholic Steatohepatitis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.)
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

Exclusion Criteria:

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
HIV infection
Use of controlled substances (including inhaled or injected drugs) or non-prescribed use of prescription drugs within 1 year of screening
If female: planned or known pregnancy, positive urine or serum pregnancy test, or lactating/breastfeeding
Previous treatment with emricasan or active investigational medication (except methacetin) in a clinical trial within 3 months prior to Day 1

Sites / Locations

Hopital Beaujon

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Arm Label

Emricasan 5mg

Emricasan 25mg

Emricasan 50mg

Placebo

Arm 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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Binary diagnosis of HVPG>=12mmHg and by the MBT derived from an algorithm developed under other Exalenz clinical studies

Full Information

NCT ID

NCT03439189

First Posted

January 29, 2018

Last Updated

December 19, 2022

Sponsor

Meridian Bioscience, Inc.

Collaborators

Conatus Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT03439189

Brief Title

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

Official Title

Companion Protocol for the ¹³C-Methacetin Breath Test Using the BreathID® MCS System for Conatus Phase 2 Study of Emricasan, an Oral Caspase Inhibitor, Under Protocol IDN-6556-14 (NCT02960204)

Study Type

Interventional

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Completed

Study Start Date

August 28, 2016 (Actual)

Primary Completion Date

April 8, 2019 (Actual)

Study Completion Date

May 13, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Meridian Bioscience, Inc.

Collaborators

Conatus Pharmaceuticals

4. Oversight

Device Product Not Approved or Cleared by U.S. FDA

Yes

Data Monitoring Committee

5. Study Description

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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

NASH - Nonalcoholic Steatohepatitis, Cirrhosis, Portal Hypertension

7. Study Design

Primary Purpose

Diagnostic

Interventional Study Model

Parallel Assignment

Model Description

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).

Masking

ParticipantCare ProviderInvestigator

Masking Description

The collaborator is responsible for the masking process.

Allocation

Randomized

Enrollment

343 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Emricasan 5mg

Arm Type

Experimental

Arm Description

Arm Title

Emricasan 25mg

Arm Type

Experimental

Arm Description

Arm Title

Emricasan 50mg

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Combination Product

Intervention Name(s)

Methacetin Breath Test

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Emricasan

Intervention Description

Investigational drug for NASH treatment in Main Conatus protocol

Intervention Type

Drug

Intervention Name(s)

Placebo oral capsule

Intervention Description

Placebo versus emricasan in Conatus NASH treatment trial

Primary Outcome Measure Information:

Title

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

Description

Time Frame

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

Secondary Outcome Measure Information:

Title

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

Description

Binary diagnosis of HVPG>=12mmHg and by the MBT derived from an algorithm developed under other Exalenz clinical studies

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.) 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 Exclusion Criteria: 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 HIV infection Use of controlled substances (including inhaled or injected drugs) or non-prescribed use of prescription drugs within 1 year of screening If female: planned or known pregnancy, positive urine or serum pregnancy test, or lactating/breastfeeding Previous treatment with emricasan or active investigational medication (except methacetin) in a clinical trial within 3 months prior to Day 1

Facility Information:

Facility Name

Hopital Beaujon

City

Clichy

ZIP/Postal Code

92118

Country

France

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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