Liver CirrhosisPhase 2PHNCT02230683

A Study of IDN-6556 in Cirrhotic Subjects With Portal Hypertension

A Phase 2 study testing IDN-6556 in people with Liver Cirrhosis and Hepatic Cirrhosis, run by Conatus Pharmaceuticals Inc. at 16 sites in United States.

Completed

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

Official record

Search all trials

Trial summary

This is an open-label pilot study to evaluate the safety, tolerability, and efficacy of IDN-6556 in treating portal hypertension in subjects with liver cirrhosis. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Liver Cirrhosis, Hepatic Cirrhosis, Portal Hypertension
What is being tested?: IDN-6556
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 23 participants
Where: 16 sitesUnited States
Study dates: Aug 2014to Jun 2015
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
Evidence of portal hypertension as evidenced by any of the following:
Splenomegaly, on imaging and/or clinical evaluation, with platelet count of <120,000 at study entry, or
Presence of small sized varices on screening endoscopy and/or collateral circulation on imaging, or
Presence of medium/large varices that have never bled and have been obliterated with endoscopic ligation
Portal hypertension defined as a hepatic venous pressure gradient (HVPG) >5 mmHg at Screening
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

Decompensated cirrhosis as defined by the presence of overt ascites (requiring diuretics), overt encephalopathy (requiring specific therapy), or history of variceal hemorrhage.
Known infection with HIV
Hepatic failure defined as total bilirubin ≥12 mg/dL
Other non-liver organ failure, including:
Renal failure defined as creatinine ≥ 2.0 mg/dL
Cerebral failure defined as hepatic encephalopathy grade III or IV

Show all 34Show fewer

Coagulation failure defined as INR ≥ 2.5 or platelets ≤ 20x109/L
Hemodynamic requirement for inotropic support
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; examples include but are not limited to:
β-blockers, including carvedilol
Nitrates
Vasopressin (or analogues)
Phosphodiesterase inhibitors (prescribed daily for pulmonary hypertension; p.r.n. use for erectile dysfunction is permitted)
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 the following drugs within 2 months of Screening:
Systemic corticosteroids
Pentoxifylline
Known or suspected use of illicit drugs or drugs of abuse (allowed if medically prescribed or indicated)
Concomitant pancreatitis
Evidence of portal vein thrombosis on Doppler ultrasound of the portal vasculature
Active inflammatory bowel disease
Diagnosed or suspected systemic lupus erythematosus (SLE) and/or rheumatoid arthritis (RA)
Autoimmune hepatitis
Hepatitis C Virus (HCV) infected subjects receiving or planning on receiving anti-viral therapy during the course of the study
Hepatitis B Virus (HBV) infected subjects who have been on stable anti-HBV therapy for less than 3 months
Hepatocellular carcinoma (HCC) at entry into the study
Active non-liver malignancies other than curatively treated skin cancer (basal cell or squamous cell carcinomas)
History or presence of clinically concerning cardiac arrhythmias, or prolongation of screening (pre-treatment) QT or QTc interval of >480 milliseconds (msec)
Significant systemic or major illness other than liver disease, including coronary artery disease, cerebrovascular disease, pulmonary disease, renal failure, serious psychiatric disease, that, in the opinion of the Investigator would preclude the subject from participating in and completing the study
Any subject that has received any investigational drug or device within 30 days of dosing or who is scheduled to receive another investigational drug or device in the course of the study
If female, known pregnancy, or has a positive urine or serum pregnancy test, or lactating/breastfeeding.

Trial locations and contacts

16 sites in 1 country.

City, postcode or hospital

16 sites in 1 country

United States16 sites

Johns Hopkins Hospital
Baltimore, Maryland, 21287
St. Luke's Health Baylor College of Medicine
Houston, Texas, 77030
University of Texas Health Science Center at Houston
Houston, Texas, 77030
University of Mississippi Medical Center
Jackson, Mississippi, 39216
North Shore University Hospital
Manhasset, New York, 11030
University of Miami
Miami, Florida, 33136
New York University Lagone Medical Center
New York, New York, 10016
Rutgers New Jersey Medical School
Newark, New Jersey, 07103
Bon Secours Mary Immaculate Hospital
Newport News, Virginia, 23602
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Albert Einstein Medical Center
Philadelphia, Pennsylvania, 19141
Bon Secours St. Mary's Hospital
Richmond, Virginia, 23226
McGuire DVAMC
Richmond, Virginia, 23249
University of Utah Hospital
Salt Lake City, Utah, 84132
Johns Hopkins Sibley Memorial Hospital
Washington D.C., District of Columbia, 20016
VA Connecticut Healthcare System
West Haven, Connecticut, 06516

Other trials in United States

About this study

Official title: An Open-Label Pilot Trial to Evaluate the Safety, Tolerability and Efficacy of IDN-6556 in Cirrhotic Subjects With Portal Hypertension

This is an open-label pilot study to evaluate the safety, tolerability, and efficacy of IDN-6556 in treating portal hypertension in subjects with liver cirrhosis.

Read the detailed description

Studies in patients with liver disease have demonstrated that cCK18 is elevated in the serum of patients and has been associated with disease severity. Studies have also shown that cCK18 is generally elevated to a higher 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. This suggests that apoptosis and caspase activity are associated with the severity of disease. IDN-6556 and its ability to inhibit inflammation and apoptosis may have a beneficial impact on both the dynamic and structural components associated with the pathogenesis of portal hypertension in cirrhosis.

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

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-013491390
25 mg BID

Study groups in NCT02230683
Study group	Role	What they receive
IDN-6556 - Overall population	Experimental	Overall evaluable population treated with IDN-6556 25 mg twice daily Receives: Drug: IDN-6556
IDN-6556 - Subgroup with Baseline HVPG < 12 mmHg	Experimental	Subgroup for patients with Baseline HVPG < 12 mmHg that have been treated with IDN-6556 25 mg twice daily Receives: Drug: IDN-6556
IDN-6556 - Subgroup Baseline HVPG ≥ 12 mmHg	Experimental	Subgroup for patients with Baseline HVPG ≥ 12 mmHg that have been treated with IDN-6556 25 mg twice daily Receives: Drug: IDN-6556

What is being measured

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

Hepatic Venous Pressure Gradient (HVPG)
Mean change of HVPG [mmHg] from Baseline to Day 28/EOT (end of treatment) for IDN-6556
Measured: Baseline to Day 28/EOT (end of treatment)
cCK18/M30
Absolute Mean Change of caspase-cleaved cytokeratin serum levels (cCK18/M30); the statistical analysis is based on the mean change in log-transformed cCK18/M30 from Baseline to Day 28/EOT (end of treatment) for IDN-6556
Measured: Change from Baseline to Day 28/EOT
Change in cCK18/M30
Median change of caspase-cleaved cytokeratin serum levels (cCK18/M30) from Baseline to Day 28/EOT (end of treatment) for IDN-6556
Measured: Baseline to Day 28/EOT (end of treatment)

Secondary outcomes (3)

Change in Alanine Aminotransferase (ALT)
Median change of ALT from Baseline to Day 28/EOT (end of treatment) for IDN-6556
Measured: Baseline to 28 days/EOT
Change in Aspartate Aminotransferase (AST)
Median change of AST from Baseline to Day 28/EOT (end of treatment) for IDN-6556
Measured: Baseline to 28 days/EOT
Concentration of Caspase 3/7 RLU
Median change of concentration of Caspase 3/7 Relative Light Units from Baseline to Day 28/EOT (end of treatment) for IDN-6556
Measured: Baseline to 28 days/EOT

Timeline

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

Aug 2014Jun 2015

First posted3 Sep 2014 (estimated)
Study startAug 2014
Primary completionMay 2015
Study completionJun 2015

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 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: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 23 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02230683
Sponsor's protocol ID: IDN-6556-11
Acronym: PH
Status last verified: Oct 2016
First submitted: 28 Aug 2014
Last updated: 21 Dec 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

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

RecruitingObservational study
Effectiveness and Clinical Outcomes of Long-term Bulevirtide Monotherapy in Patients With HDV-related Compensated Cirrhosis
Hepatitis D
Recruiting
Optimal Treatment Strategy for Spontaneous Bacterial Peritonitis
Spontaneous Bacterial Peritonitis, Paracentesis
RecruitingObservational study
The Value of Spleen Thickness and Spleen Diameter for Gastroesophageal Varices Diagnosis in Compensated Cirrhosis
Liver Cirrhosis, Gastroesophageal Varices
Recruiting
CirrhosisRx CDS System
Cirrhosis, Decision Support Systems, Clinical
RecruitingPhase 3
Trial to Evaluate ALN-CIDEB in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Metabolic Dysfunction-Associated Steatotic Liver Disease, MASLD

All Liver Cirrhosis trials

Study at a glance

From the registry record, last updated by the sponsor on 21 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-Label Pilot Trial to Evaluate the Safety, Tolerability and Efficacy of IDN-6556 in Cirrhotic Subjects With Portal Hypertension
ClinicalTrials.gov ID: NCT02230683
Acronym / sponsor ID: PH / IDN-6556-11
Conditions: Liver Cirrhosis, Hepatic Cirrhosis, Portal Hypertension
Keywords: Liver Cirrhosis, Hepatic Cirrhosis, Portal Hypertension
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 23 participants (actual)
Lead sponsor: Conatus Pharmaceuticals Inc.Industry (pharma, biotech, devices)
Study start: Aug 2014
Primary completion: May 2015 (actual)
Study completion: Jun 2015 (actual)
First posted: 3 Sep 2014 (estimated)
Results: Posted 21 Dec 2016

Clinical summary

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

This is an open-label pilot study to evaluate the safety, tolerability, and efficacy of IDN-6556 in treating portal hypertension in subjects with liver cirrhosis.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
IDN-6556 - Overall population	Experimental	Drug: IDN-6556Overall evaluable population treated with IDN-6556 25 mg twice daily
IDN-6556 - Subgroup with Baseline HVPG < 12 mmHg	Experimental	Drug: IDN-6556Subgroup for patients with Baseline HVPG < 12 mmHg that have been treated with IDN-6556 25 mg twice daily
IDN-6556 - Subgroup Baseline HVPG ≥ 12 mmHg	Experimental	Drug: IDN-6556Subgroup for patients with Baseline HVPG ≥ 12 mmHg that have been treated with IDN-6556 25 mg twice daily

Who may qualify

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

Key inclusion criteria (8 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
Evidence of portal hypertension as evidenced by any of the following:
Portal hypertension defined as a hepatic venous pressure gradient (HVPG) >5 mmHg at Screening
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 (34 listed)

Decompensated cirrhosis as defined by the presence of overt ascites (requiring diuretics), overt encephalopathy (requiring specific therapy), or history of variceal hemorrhage.
Known infection with HIV
Hepatic failure defined as total bilirubin ≥12 mg/dL
Other non-liver organ failure, including:
Child-Pugh score of 10-15 (Child-Pugh C classification)

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-01349139025 mg BID	Drug	IDN-6556 - Overall population, IDN-6556 - Subgroup Baseline HVPG ≥ 12 mmHg, IDN-6556 - Subgroup with Baseline HVPG < 12 mmHg

Primary outcome

Hepatic Venous Pressure Gradient (HVPG)
Time frame: Baseline to Day 28/EOT (end of treatment)
Mean change of HVPG [mmHg] from Baseline to Day 28/EOT (end of treatment) for IDN-6556
cCK18/M30
Time frame: Change from Baseline to Day 28/EOT
Absolute Mean Change of caspase-cleaved cytokeratin serum levels (cCK18/M30); the statistical analysis is based on the mean change in log-transformed cCK18/M30 from Baseline to Day 28/EOT (end of treatment) for IDN-6556
Change in cCK18/M30
Time frame: Baseline to Day 28/EOT (end of treatment)
Median change of caspase-cleaved cytokeratin serum levels (cCK18/M30) from Baseline to Day 28/EOT (end of treatment) for IDN-6556

3 secondary outcomes

Change in Alanine Aminotransferase (ALT)
Time frame: Baseline to 28 days/EOT
Change in Aspartate Aminotransferase (AST)
Time frame: Baseline to 28 days/EOT
Concentration of Caspase 3/7 RLU
Time frame: Baseline to 28 days/EOT

Results and safety

Results posted to the registry on 21 Dec 2016, 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	23	22

Primary outcome: Hepatic Venous Pressure Gradient (HVPG)

Time frame: Baseline to Day 28/EOT (end of treatment). Mean (Standard Deviation). Unit: mmHg

Measure	IDN-6556 - Overall Population n = 22	IDN-6556 - Subgroup With HVPG < 12 mmHg n = 10	IDN-6556 - Subgroup HVPG ≥ 12 mmHg n = 12
Baseline	15.2 (7.68)	8.05 (1.88)	20.62 (5.59)
Day 28/EOT	14.1 (6.40)	10.0 (3.86)	17.6 (6.10)
Change From Baseline	-1.14 (4.57)	1.90 (3.15)	-3.67 (4.05)

IDN-6556 - Overall Population: within group change: -1.14 (95% CI -3.16 to 0.89), p = 0.257, Paired t-test
IDN-6556 - Subgroup With HVPG < 12 mmHg: within group change: 1.90 (95% CI -0.52 to 4.32), p = 0.1174, ANCOVA
IDN-6556 - Subgroup HVPG ≥ 12 mmHg: within group change: -3.67 (95% CI -5.88 to -1.46), p = 0.0025, ANCOVA

Population analysed: 23 subjects were enrolled, of whom 22 were evaluable for the HVPG endpoint. 1 subject discontinued at day 1.

Primary outcome: cCK18/M30

Time frame: Change from Baseline to Day 28/EOT. Mean (Standard Deviation). Unit: U/L

Measure	IDN-6556 - Overall Population n = 23	IDN-6556 - Subgroup With HVPG < 12 mmHg n = 10	IDN-6556 - Subgroup HVPG ≥ 12 mmHg n = 13
Value	-47.1 (122.23)	-74.3 (99.02)	-26.2 (137.64)

IDN-6556 - Overall Population: within group change: -0.22 (95% CI -0.42 to -0.03), p = 0.026, ANCOVA
IDN-6556 - Subgroup With HVPG < 12 mmHg: within group change: -0.46 (95% CI -0.72 to -0.21), p = 0.001, ANCOVA
IDN-6556 - Subgroup HVPG ≥ 12 mmHg: within group change: -0.04 (95% CI -0.26 to 0.18), p = 0.72, ANCOVA

Primary outcome: Change in cCK18/M30

Time frame: Baseline to Day 28/EOT (end of treatment). Median (Full Range). Unit: U/L

Measure	IDN-6556 - Overall Population n = 23	IDN-6556 - Subgroup With HVPG < 12 mmHg n = 10	IDN-6556 - Subgroup HVPG ≥ 12 mmHg n = 13
Baseline	191.0 (78 to 994)	189.0 (126 to 442)	221.0 (78 to 994)
Day 28/EOT	143.0 (48 to 548)	124.5 (48 to 291)	186.0 (94 to 548)
Change From Baseline at Day 28	-21.0 (-446 to 119)	-52.5 (-323 to 45)	12.0 (-446 to 119)

IDN-6556 - Overall Population: Hodges-Lehmann: -21 (95% CI -60 to 13), p = 0.105, Wilcoxon (Mann-Whitney)
IDN-6556 - Subgroup With HVPG < 12 mmHg: Hodges-Lehmann: -52.5 (95% CI -109 to -6), p = 0.016, Wilcoxon (Mann-Whitney)
IDN-6556 - Subgroup HVPG ≥ 12 mmHg: Hodges-Lehmann: 12 (95% CI -60 to 13), p = 0.839, Wilcoxon (Mann-Whitney)

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse Events were collected for a period of 8 months.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
IDN-6556	1 of 23 (4.3%)	15 of 23 (65.2%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Liver Cirrhosis

RecruitingObservational study
Effectiveness and Clinical Outcomes of Long-term Bulevirtide Monotherapy in Patients With HDV-related Compensated Cirrhosis
Hepatitis D
Recruiting
Optimal Treatment Strategy for Spontaneous Bacterial Peritonitis
Spontaneous Bacterial Peritonitis, Paracentesis
RecruitingObservational study
The Value of Spleen Thickness and Spleen Diameter for Gastroesophageal Varices Diagnosis in Compensated Cirrhosis
Liver Cirrhosis, Gastroesophageal Varices
Recruiting
CirrhosisRx CDS System
Cirrhosis, Decision Support Systems, Clinical
RecruitingPhase 3
Trial to Evaluate ALN-CIDEB in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Metabolic Dysfunction-Associated Steatotic Liver Disease, MASLD

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.

David Hagerty, MD study chair

Conatus Pharmaceuticals Inc.

16 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 16 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 8 inclusion and 34 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 21 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 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. 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 21 Dec 2016). 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?

Hepatic Venous Pressure Gradient (HVPG) (time frame: Baseline to Day 28/EOT (end of treatment)). The study lists 3 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 NCT02230683.

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 21 Dec 2016.