Liver CirrhosisPhase 2LCNCT02230670

A Study of IDN-6556 in Subjects With Liver Cirrhosis

A Phase 2 study testing IDN-6556 in people with Liver Cirrhosis and Hepatic Cirrhosis, run by Conatus Pharmaceuticals Inc. at 28 sites in United States.

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

This is a multicenter study to see if treatment with IDN-6556 can help improve the liver function of patients with liver cirrhosis with Model for End-Stage Liver Disease scores between 11-18. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Liver Cirrhosis, Hepatic Cirrhosis
What is being tested?: IDN-6556
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 87 participants
Where: 28 sitesUnited States
Study dates: Aug 2014to Jan 2016
Phase: Phase 2
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 of minimum adult legal age (according to local laws for signing the informed consent document), able to provide written informed consent, and able to understand and willing to comply with the requirements of the study
Clinical, radiological, or biochemical evidence of liver cirrhosis
Model for End-Stage Liver Disease (MELD) Score of 11 to 18 during the Screening period
Willingness to utilize two reliable forms of contraception (for both males and females of childbearing potential) from Screening to one month after the last dose of study drug.

Who cannot join

Known infection with human immunodeficiency virus (HIV)
Auto-immune hepatitis
Subjects with evidence of uncontrolled infection, defined as persistent bacterial culture positivity despite adequate antibiotic therapy
HCV infected subjects who are receiving or plan to receive anti-viral therapy during the study
Untreated esophageal varices with high risk stigmata for hemorrhage
Variceal hemorrhage within 3 months of Screening

Show all 21Show fewer

Ascites not adequately controlled on stable background medication
Other non-liver organ failure
Child-Pugh score of 10-15 (Child-Pugh C classification)
Use of vasoactive drugs (at or within 3 months of Screening) that may impair hepatic blood flow
Change in dose or regimen within 3 months of Screening of:
Fibrates or statins
Angiotensin II receptor antagonist or angiotensin converting enzyme (ACE) inhibitor
Use of chronic anticoagulation therapy including but not limited to Vitamin K/Factor Xa antagonists/inhibitors
Use of the following drugs within 2 months of Screening:
Systemic corticosteroids
Known or suspected use of illicit drugs or drugs of abuse (allowed if medically prescribed or indicated)
Concomitant pancreatitis
Active inflammatory bowel disease
Diagnosed or suspected systemic lupus erythematosus (SLE) and/or rheumatoid arthritis (RA)
Subjects with active or history of malignancies other than hepatocellular carcinoma (HCC) within Milan criteria or curatively treated skin cancer (basal cell or squamous cell carcinomas), unless adequately treated or in complete remission for five or more years

Trial locations and contacts

28 sites in 1 country.

City, postcode or hospital

28 sites in 1 country

United States28 sites

Piedmont Atlanta Hospital
Atlanta, Georgia, 30309
University of Alabama at Birmingham
Birmingham, Alabama, 35233
University of Chicago
Chicago, Illinois, 60637
University of Cincinnati Physicians Company, LLC
Cincinnati, Ohio, 45267
Henry Ford Hospital
Detroit, Michigan, 48202
Baylor All Saints Medical Center
Fort Worth, Texas, 76104
University of Florida
Gainesville, Florida, 32610
Baylor College of Medicine
Houston, Texas, 77030
Baylor St. Luke's Medical Center
Houston, Texas, 77030
UT Health Science Center at Houston
Houston, Texas, 77030
Indiana University
Indianapolis, Indiana, 46202
Scripps Clinic
La Jolla, California, 92037
Loma Linda University Medical Center
Loma Linda, California, 92354
Cedar-Sinai Medical Center
Los Angeles, California, 90048
University of Louisville
Louisville, Kentucky, 40202
North Shore University Hospital
Manhasset, New York, 11030
Loyola University Medical Cente
Maywood, Illinois, 60153
University of Miami
Miami, Florida, 33136
NYU Medical Center
New York, New York, 10016
Mt. Sinai School of Medicine
New York, New York, 10029
Rutgers New Jersey Medical School
Newark, New Jersey, 07103
Bon Secours Mary Immaculate Hospital
Newport News, Virginia, 23602
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Einstein Healthcare Network
Philadelphia, Pennsylvania, 19141
Bon Secours St. Mary's Hospital of Richmond, Inc.
Richmond, Virginia, 23226
University of Utah Hospital
Salt Lake City, Utah, 84132
Univeristy of California, San Diego
San Diego, California, 92093
California Pacific Medical Center
San Francisco, California, 94115

Other trials in United States

About this study

Official title: A Multicenter, Double-Blind, Placebo Controlled Study to Evaluate the Safety, Tolerability and Efficacy of IDN-6556 in Subjects With Liver Cirrhosis

This is a multicenter study to see if treatment with IDN-6556 can help improve the liver function of patients with liver cirrhosis with Model for End-Stage Liver Disease scores between 11-18.

Read the detailed description

Numerous studies have shown that caspase cleaved cytokeratin 18 (cCK18) is elevated in the serum of liver disease patients and has been associated with disease severity, thus associating both excessive apoptosis and caspase activity with disease. Studies have also shown that caspase cleaved cytokeratin 18 is generally elevated to an even greater degree in cirrhosis than in other liver diseases. In addition, increasing stages of cirrhosis from Child-Pugh A, Child-Pugh B to Child-Pugh C are associated with progressively higher levels of caspase cleaved cytokeratin 18. Therefore, it appears that apoptosis and caspase activity tend to correlate with the stage of cirrhosis. A caspase inhibitor like IDN-6556 could have clinical utility by reducing the rate of apoptosis in cirrhotic patients and potentially reduce the progression of disease as determined by clinical markers of progression.

Conditions: Liver Cirrhosis, Hepatic Cirrhosis
Being tested: IDN-6556, Placebo
Keywords: Liver Cirrhosis, Hepatic Cirrhosis
Medical subject headings: Liver Cirrhosis

What participants receive

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

IDN-6556Drug
Also called emricasan, PF-03491390
25 mg BID
PlaceboDrug

Study groups in NCT02230670
Study group	Role	What they receive
IDN-6556	Experimental	25 mg BID of IDN-6556 Receives: Drug: IDN-6556
Placebo	Placebo comparator	Placebo BID Receives: Drug: Placebo

What is being measured

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

Change From Baseline at Month 3 in cCK18/M30
Baseline, Month 3, and change between for cCK18/M30
Measured: 3 months
Change From Baseline at Month 3 in cCK18/M30
Data was log-transformed for analysis purposes
Measured: 3 months

Secondary outcomes (1)

Change From Baseline to Month 3 in MELD Score
The Model for End-Stage Liver Disease (MELD) is a scoring system for assessing the severity of chronic liver disease and uses the subject's values for total bilirubin, serum creatinine, and the international normalized ratio (INR) for prothrombin time to predict survival. MELD is calculated according to the following formula:
MELD = 3.78×ln[serum bilirubin (mg/dL)] + 11.2×ln[INR] + 9.57×ln[serum creatinine (mg/dL)] + 6.43
MELD scores are reported as whole numbers, so the result of the equation above is rounded. Notes: If the patient has been dialyzed twice within the last 7 days, then the value for serum creatinine used should be 4.0. Any value less than one is given a value of 1 (i.e. if bilirubin is 0.8, a value of 1.0 is used) to prevent the occurrence of scores below 0 (the natural logarithm of 1 is 0, and any value below 1 would yield a negative result). The higher the MELD score the more severe the disease state.
Measured: 3 Months

Timeline

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

Aug 2014Jan 2016

First posted3 Sep 2014 (estimated)
Study startAug 2014
Primary completionJan 2016
Study completionJan 2016

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.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Liver CirrhosisStudies 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
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 87 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02230670
Sponsor's protocol ID: IDN-6556-10
Acronym: LC
Status last verified: Jun 2017
First submitted: 28 Aug 2014
Last updated: 5 Jul 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Frenette CT, Morelli G, Shiffman ML, Frederick RT, Rubin RA, Fallon MB, Cheng JT, Cave M, Khaderi SA, Massoud O, Pyrsopoulos N, Park JS, Robinson JM, Yamashita M, Spada AP, Chan JL, Hagerty DT. Emricasan Improves Liver Function in Patients With Cirrhosis and High Model for End-Stage Liver Disease Scores Compared With Placebo. Clin Gastroenterol Hepatol. 2019 Mar;17(4):774-783.e4. doi: 10.1016/j.cgh.2018.06.012. Epub 2018 Jun 18.
PubMed 29913280

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

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Study at a glance

From the registry record, last updated by the sponsor on 5 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter, Double-Blind, Placebo Controlled Study to Evaluate the Safety, Tolerability and Efficacy of IDN-6556 in Subjects With Liver Cirrhosis
ClinicalTrials.gov ID: NCT02230670
Acronym / sponsor ID: LC / IDN-6556-10
Conditions: Liver Cirrhosis, Hepatic Cirrhosis
Keywords: Liver Cirrhosis, Hepatic Cirrhosis
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 87 participants (actual)
Lead sponsor: Conatus Pharmaceuticals Inc.Industry (pharma, biotech, devices)
Study start: Aug 2014
Primary completion: Jan 2016 (actual)
Study completion: Jan 2016 (actual)
First posted: 3 Sep 2014 (estimated)
Results: Posted 5 Jul 2017

Clinical summary

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

This is a multicenter study to see if treatment with IDN-6556 can help improve the liver function of patients with liver cirrhosis with Model for End-Stage Liver Disease scores between 11-18.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
IDN-6556	Experimental	Drug: IDN-655625 mg BID of IDN-6556
Placebo	Placebo comparator	Drug: PlaceboPlacebo BID

Who may qualify

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

Key inclusion criteria (4 listed)

Male or female subjects of minimum adult legal age (according to local laws for signing the informed consent document), able to provide written informed consent, and able to understand and willing to comply with the requirements of the study
Clinical, radiological, or biochemical evidence of liver cirrhosis
Model for End-Stage Liver Disease (MELD) Score of 11 to 18 during the Screening period
Willingness to utilize two reliable forms of contraception (for both males and females of childbearing potential) from Screening to one month after the last dose of study drug.

Key exclusion criteria (21 listed)

Known infection with human immunodeficiency virus (HIV)
Auto-immune hepatitis
Subjects with evidence of uncontrolled infection, defined as persistent bacterial culture positivity despite adequate antibiotic therapy
HCV infected subjects who are receiving or plan to receive anti-viral therapy during the study
Untreated esophageal varices with high risk stigmata for hemorrhage

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
IDN-6556Also: emricasan, PF-0349139025 mg BID	Drug	IDN-6556
Placebo	Drug	Placebo

Primary outcome

Change From Baseline at Month 3 in cCK18/M30
Time frame: 3 months
Baseline, Month 3, and change between for cCK18/M30
Change From Baseline at Month 3 in cCK18/M30
Time frame: 3 months
Data was log-transformed for analysis purposes

1 secondary outcome

Change From Baseline to Month 3 in MELD Score
Time frame: 3 Months

Results and safety

Results posted to the registry on 5 Jul 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
IDN-6556	44	40
Placebo	42	34

Primary outcome: Change From Baseline at Month 3 in cCK18/M30

Time frame: 3 months. Median (Full Range). Unit: U/L

Measure	IDN-6556 n = 44	Placebo n = 42
Baseline	293.5 (66 to 1857)	257.5 (104 to 6994)
Month 3	288.5 (39 to 1583)	285.0 (115 to 19710)

Population analysed: FAS

Primary outcome: Change From Baseline at Month 3 in cCK18/M30

Time frame: 3 months. Least squares mean (Standard Error). Unit: U/L

Measure	IDN-6556 n = 44	Placebo n = 42
Log-transformed Values	-0.049 (0.057)	0.090 (0.058)
Percent (%) Relative Change	-4.6 (5.9)	9.3 (5.9)

IDN-6556 vs Placebo: Mean Difference (Final Values): -0.140 (95% CI -0.302 to 0.023), p = 0.091, ANCOVA
IDN-6556 vs Placebo: Mean Difference (Final Values): -0.20 (95% CI -0.41 to 0.01), p = 0.041, ANCOVA

Population analysed: Full analysis set

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Adverse events were collected in a blinded fashion from baseline to Month 3. Double-blind adverse events are presented here. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
IDN-6556 (Baseline-Month 3)	6 of 44 (13.6%)	34 of 44 (77.3%)	0 of 44
Placebo (Baseline-Month 3)	5 of 42 (11.9%)	30 of 42 (71.4%)	0 of 42

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 29913280Frenette CT, Morelli G, Shiffman ML, Frederick RT, Rubin RA, Fallon MB, Cheng JT, Cave M, Khaderi SA, Massoud O, Pyrsopoulos N, Park JS, Robinson JM, Yamashita M, Spada AP, Chan JL, Hagerty DT. Emricasan Improves Liver Function in Patients With Cirrhosis and High Model for End-Stage Liver Disease Scores Compared With Placebo. Clin Gastroenterol Hepatol. 2019 Mar;17(4):774-783.e4. doi: 10.1016/j.cgh.2018.06.012. Epub 2018 Jun 18.

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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.

Dave Hagerty, MD study chair

Conatus Pharmaceuticals Inc.

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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing IDN-6556 in people with Liver Cirrhosis and Hepatic Cirrhosis, run by Conatus Pharmaceuticals Inc. at 28 sites in United States.

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 4 inclusion and 21 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 5 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in United States. 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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Jul 2017). 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?

Change From Baseline at Month 3 in cCK18/M30 (time frame: 3 months). The study lists 2 primary outcomes in all. 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 NCT02230670, which also lists 1 linked publication.

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 5 Jul 2017.