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

Primary Purpose

Decompensated Cirrhosis

Status

Terminated

Phase

Locations

United States

Study Type

Interventional

Intervention

Methacetin Breath Test

Emricasan

Placebo oral capsule

About this trial

This is an interventional diagnostic trial for Decompensated Cirrhosis

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.)
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

Sites / Locations

Florida Digestive Health Specialists Research Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Emricasan 25mg

Emricasan 5mg

Placebo

Arm 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.

Outcomes

Primary Outcome Measures

Number of Subjects Experiencing a High Risk Event Based on a 5.5%/Hour Cut-off

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

Number of Subjects Experiencing a High Risk Event Based on a 7.5 %/Hour Cut-off

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.

Full Information

NCT ID

NCT03462576

First Posted

March 6, 2018

Last Updated

December 19, 2022

Sponsor

Meridian Bioscience, Inc.

Collaborators

Conatus Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT03462576

Brief Title

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

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-6556-17

Study Type

Interventional

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Terminated

Why Stopped

Sponsor of Trial decision

Study Start Date

June 28, 2017 (Actual)

Primary Completion Date

July 15, 2019 (Actual)

Study Completion Date

July 15, 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

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) ].

6. Conditions and Keywords

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

Decompensated Cirrhosis

7. Study Design

Primary Purpose

Diagnostic

Interventional Study Model

Parallel Assignment

Model 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. All subjects will continue treatment until the last subject in the study reaches 48 weeks in the study. At least 30% of subjects randomized should have baseline MELD score ≥15 and ≤20. For each subject, the study will consist of: Screening period of up to 4 weeks Randomized, double-blind treatment period of at least 48 weeks A follow-up visit 2 weeks after completion of study drug treatment The duration of each subject's participation will be at least 54 weeks for those completing the entire study.

Masking

ParticipantCare ProviderInvestigator

Masking Description

The collaborator is responsible for the masking process.

Allocation

Randomized

Enrollment

199 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Emricasan 25mg

Arm Type

Experimental

Arm 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.

Arm Title

Emricasan 5mg

Arm Type

Experimental

Arm 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.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm 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.

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 carbon13 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 Experiencing a High Risk Event Based on a 5.5%/Hour Cut-off

Description

Time Frame

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

Secondary Outcome Measure Information:

Title

Number of Subjects Experiencing a High Risk Event Based on a 7.5 %/Hour Cut-off

Description

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.

Time Frame

1 hour for MBT for assessment of this diagnostic 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.) 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

Facility Information:

Facility Name

Florida Digestive Health Specialists Research Institute

City

Lakewood Ranch

State/Province

Florida

ZIP/Postal Code

34211

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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