NASH - Nonalcoholic SteatohepatitisNCT03439189

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

A study testing Methacetin Breath Test and Emricasan in people with NASH - Nonalcoholic Steatohepatitis and Cirrhosis, run by Meridian Bioscience, Inc. at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: NASH - Nonalcoholic Steatohepatitis, Cirrhosis, Portal Hypertension
What is being tested?: Methacetin Breath Test and Emricasan
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 343 participants
Where: 1 siteFrance
Study dates: 28 Aug 2016to 13 May 2019
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 19Show fewer

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

Trial locations and contacts

1 site in 1 country.

France1 site

Hopital Beaujon
Clichy, 92118

Other trials in France

About this study

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)

Read the 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.

Conditions: NASH - Nonalcoholic Steatohepatitis, Cirrhosis, Portal Hypertension
Being tested: Methacetin Breath Test, Emricasan, Placebo oral capsule
Medical subject headings: Non-alcoholic Fatty Liver Disease, Fibrosis, Hypertension, Portal

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Methacetin Breath TestCombination 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.
EmricasanDrug
Investigational drug for NASH treatment in Main Conatus protocol
Placebo oral capsuleDrug
Placebo versus emricasan in Conatus NASH treatment trial

Study groups in NCT03439189
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: 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. Receives: Combination Product: Methacetin Breath Test; Drug: Placebo oral capsule

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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
Binary diagnosis of HVPG>=12mmHg and by the MBT derived from an algorithm developed under other Exalenz clinical studies
Measured: 1 hour for MBT for assessment of this diagnostic secondary outcome assessed during screening

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Aug 201613 May 2019

First posted20 Feb 2018
Study start28 Aug 2016
Primary completion8 Apr 2019
Study completion13 May 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for NASH - Nonalcoholic SteatohepatitisStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Primary purpose: Diagnosis
Allocation: Randomised
Intervention model: Parallel groups
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: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 343 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03439189
Sponsor's protocol ID: CON-EX-0616
Status last verified: Dec 2022
First submitted: 29 Jan 2018
Last updated: 20 Dec 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 1/2
A Study to Evaluate ALN-CIDEB in Adult Participants With Metabolic Dysfunction-Associated Steatotic Liver Disease or With Metabolic Dysfunction-Associated Steatohepatitis (MASLD/MASH)
Metabolic Dysfunction-Associated Steatotic Liver Disease, Metabolic Dysfunction-Associated Steatohepatitis
Active, not recruiting
Target of Suv420h1/2 in Hepatocytes
NAFLD
Active, not recruitingPhase 3
A Phase 3 Study Evaluating Efficacy and Safety of Lanifibranor Followed by an Active Treatment Extension in Adult Patients With (NASH) and Fibrosis Stages F2 and F3 ( NATiV3 )
NASH - Nonalcoholic Steatohepatitis
Not yet recruitingPhase 2/3
Evaluating the Safety and Efficacy of Roflumilast in the Treatment of Nonalcoholic Fatty Liver Disease Patients
NAFLD (Nonalcoholic Fatty Liver Disease)
Not yet recruitingPhase 2/3
Evaluating the Safety and Efficacy of Rupatadine in the Treatment of Nonalcoholic Fatty Liver Disease Patients.
NAFLD (Nonalcoholic Fatty Liver Disease)

All NASH - Nonalcoholic Steatohepatitis trials

Study at a glance

From the registry record, last updated by the sponsor on 20 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

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)
ClinicalTrials.gov ID: NCT03439189
Acronym / sponsor ID: CON-EX-0616
Conditions: NASH - Nonalcoholic Steatohepatitis, Cirrhosis, Portal Hypertension
Study type: Interventional
Recruitment status: Completed
Enrolment: 343 participants (actual)
Lead sponsor: Meridian Bioscience, Inc.Industry (pharma, biotech, devices)
Collaborators: Conatus Pharmaceuticals Inc.
Study start: 28 Aug 2016 (actual)
Primary completion: 8 Apr 2019 (actual)
Study completion: 13 May 2019 (actual)
First posted: 20 Feb 2018 (actual)
Results: Posted 4 Sep 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Diagnosis
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 4
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).

Arm	Type	Receives
Emricasan 5mg	Experimental	Combination Product: Methacetin Breath Test, Drug: EmricasanSubjects 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.
Emricasan 25mg	Experimental	Combination Product: Methacetin Breath Test, Drug: EmricasanSubjects 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.
Emricasan 50mg	Experimental	Combination Product: Methacetin Breath Test, Drug: EmricasanSubjects 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.
Placebo	Placebo comparator	Combination Product: Methacetin Breath Test, Drug: Placebo oral capsuleSubjects 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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

Key exclusion criteria (19 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Methacetin Breath TestA 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.	Combination product	Emricasan 25mg, Emricasan 50mg, Emricasan 5mg, Placebo
EmricasanInvestigational drug for NASH treatment in Main Conatus protocol	Drug	Emricasan 25mg, Emricasan 50mg, Emricasan 5mg
Placebo oral capsulePlacebo versus emricasan in Conatus NASH treatment trial	Drug	Placebo

Primary outcome

Number of Subjects With Matched Clinically Significant Portal Hypertension Based on Hepatic Venous Pressure Gradient (HVPG) and Methacetin Breath Test (MBT)
Time frame: 1 hour for MBT related to assessment of this diagnostic primary outcome assesses during screening
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 secondary outcome

Number of Matched Subjects With Significant Portal Hypertension (Defined as HVPG>=12mmHg) Based on HVPG and MBT
Time frame: 1 hour for MBT for assessment of this diagnostic secondary outcome assessed during screening

Results and safety

Results posted to the registry on 4 Sep 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
ACLD With NASH	343	261

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

Time frame: 1 hour for MBT related to assessment of this diagnostic primary outcome assesses during screening. Count of participants. Unit: Participants

Measure	Subjects With CSPH n = 261
Value	190

Population analysed: Diagnostic endpoints used screening measurements taken prior to study drug administration, therefore no treatment effect was relevant. In addition, for the event prediction endpoints, the treatment covariate was tested for significance, and was found to be non-significant, thus removed from the final predicting model. As such, arms were combined.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Data was collected for a duration of approximately 1 year to observe the effect of the treatment. Additional MBTs after 24 and 48 weeks were performed to enable Conatus to assess the ability of MBT to identify improvement in liver function due to treatment, if relevant. Each MBT duration is 1 hour. The subsequent MBTs were not relevant to companion protocol primary and secondary efficacy diagnostic endpoints listed above, but additional safety information regarding these MBTs was collected.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
ACLD With NASH	0 of 343 (0%)	2 of 343 (0.6%)	0 of 343

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 20 Dec 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for NASH - Nonalcoholic Steatohepatitis

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Methacetin Breath Test and Emricasan in people with NASH - Nonalcoholic Steatohepatitis and Cirrhosis, run by Meridian Bioscience, Inc. at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Subjects With Matched Clinically Significant Portal Hypertension Based on Hepatic Venous Pressure Gradient (HVPG) and Methacetin Breath Test (MBT) (time frame: 1 hour for MBT related to assessment of this diagnostic primary outcome assesses during screening). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03439189.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2022.