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

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-6556-14 (NCT02960204)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03439189
• Other study ID #: CON-EX-0616
• Status: Completed
• Start date: August 28, 2016
• Est. completion date: May 13, 2019

Study information

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

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 343
• Est. completion date: May 13, 2019
• Est. primary completion date: April 8, 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. 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

Related Conditions & MeSH terms

• Cirrhosis
• Fatty Liver
• Hypertension, Portal
• NASH - Nonalcoholic Steatohepatitis
• Non-alcoholic Fatty Liver Disease
• Portal Hypertension

Intervention

Combination Product:
• Methacetin Breath Test
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.

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
France	Hopital Beaujon	Clichy

Sponsors (2)

Lead Sponsor	Collaborator
Meridian Bioscience, Inc.	Conatus Pharmaceuticals

Country where clinical trial is conducted

France, 

Outcome

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