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

Decompensated Cirrhosis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03462576
• Other study ID #: CON-EX-0217
• Status: Terminated
• Start date: June 28, 2017
• Est. completion date: July 15, 2019

Study information

• Verified date: December 2022
• Source: Meridian Bioscience, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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) ].

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 199
• Est. completion date: July 15, 2019
• Est. primary completion date: July 15, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Decompensated Cirrhosis
• Fibrosis

Intervention

Combination Product:
• Methacetin Breath Test
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.

Drug:
• Emricasan
Investigational drug for NASH treatment in Main Conatus protocol
• Placebo oral capsule
Placebo versus emricasan in Conatus NASH treatment trial

Locations

Country	Name	City	State
United States	Florida Digestive Health Specialists Research Institute	Lakewood Ranch	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Meridian Bioscience, Inc.	Conatus Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	1 hour for MBT for assessment of this diagnostic outcome assessed during screening
Secondary	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.	1 hour for MBT for assessment of this diagnostic outcome assessed during screening