Acute on Chronic Hepatic FailurePhase 2NCT01937130
Pharmacokinetic and Pharmacodynamic Study of IDN-6556 in ACLF
A Phase 2 study testing IDN-6556 in people with Acute on Chronic Hepatic Failure and Acute Liver Failure, run by Conatus Pharmaceuticals Inc. at 26 sites in 2 countries.
Trial summary
The study will evaluate the pharmacokinetics, pharmacodynamics, safety and preliminary efficacy of IDN-6556 in subjects with cirrhosis of the liver who are hospitalized for more than 24 hours due to acute deterioration of liver function. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute on Chronic Hepatic Failure, Acute Liver Failure, Liver Cirrhosis
- What is being tested?
- IDN-6556
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 26 sitesin 2 countries
- Study dates
- Sep 2013to Feb 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 understand and comply with the requirements of the study
- Subjects with a clinical, radiological and/or histological diagnosis of cirrhosis
- Subjects having not required hospital admission within 4 weeks of screening for a complication of cirrhosis
- Subjects with an acute deterioration of liver function
- Subjects who meet one of the following criteria:
- Subjects with renal failure (defined as creatinine ≥ 2.0 to ≤ 3.4 mg/dL)
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- Subjects with other single organ failure with i. Renal impairment (defined as an increase in creatinine of > 0.3 mg/dL from either an established prior Baseline level or if applicable, upon admission to hospital if prior level is unavailable; for inclusion, the creatinine level must be raised above normal levels), and/or ii. Hepatic encephalopathy grade I or II
- Subjects with two organ failures
- If a subject received steroids for alcohol-induced acute liver failure, he/she must be unresponsive to steroid therapy. Responsiveness is based on investigator discretion.
- 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 HIV
- Subjects with cirrhosis who develop decompensation at any time in the postoperative period following partial hepatectomy
- Subjects with evidence of uncontrolled infection defined as persistent bacterial culture positivity despite adequate antibiotic therapy
- Subjects with clinical evidence of disseminated intravascular coagulation
- Subjects with chronic and/or pre-existing kidney disease defined as eGFR (estimated glomerular filtration rate) of less than 30 mL/min for 3 months or longer
- Subjects who are hypotensive (defined as mean arterial pressure <70 mmHg) or require the use of inotropic support
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- Subjects with evidence of significant and/or uncontrolled bleeding
- Subjects requiring mechanical ventilation
- 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
- Subjects previously exposed to IDN-6556
- History or presence of clinically concerning cardiac arrhythmias, or prolongation of Screening (pre-treatment) QT or QTc interval of > 480 milliseconds (msec)
Trial locations and contacts
26 sites in 2 countries.
26 sites in 2 countries
United Kingdom15 sites
Basildon and Thurrock University Hospital
Basildon, SS16 5NL
Blackpool Victoria Hospital
Blackpool, FY3 8NR
Bristol Royal Infirmary
Bristol, BS2 8HW
Ninewells Hospital
Dundee, DD1 9SY
Glasgow Royal Infirmary
Glasgow
Leicester Royal Infirmary
Leicester, LE1 5WW
Royal Liverpool University Hospital
Liverpool, L7 8XP
University College London, Royal Free Hospital
London, NW3 2PF
Royal London Hospital
London
Central Manchester University Hospitals NHS Trust
Manchester, M13 9WL
Freeman Hospital
Newcastle upon Tyne, NE7 7DN
Nottingham University Hospitals NHS Trust
Nottingham, NG7 2UH
Derriford Hospital
Plymouth
Queen Alexandra Hospital
Portsmouth, PO6 3LY
Singleton Hospital
Swansea, Wales, SA2 8QA
United States11 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35294
University of Mississippi Medical Center
Jackson, Mississippi, 39216
University of Kansas Medical Center
Kansas City, Kansas, 66160
Scripps Clinic
La Jolla, California, 92037
Univerisity of Louisville Liver Research Center
Louisville, Kentucky, 40202
University of Utah
Salt Lake City, Utah, 84132
VA San Diego Healthcare System
San Diego, California, 92161
Sutter Pacific Medical Foundation
San Francisco, California, 94115
University of Washington Harborview Medical Center
Seattle, Washington, 98104
Montefiore Medical Center
The Bronx, New York, 10467
Georgetown University Hospital
Washington D.C., District of Columbia, 20007
About this study
Official title: A Placebo-Controlled, Multicenter, Double-Blind, Randomized, Pharmacokinetic and Pharmacodynamic Trial of IDN-6556 in Subjects With Acute-on-Chronic Liver Failure
The study will evaluate the pharmacokinetics, pharmacodynamics, safety and preliminary efficacy of IDN-6556 in subjects with cirrhosis of the liver who are hospitalized for more than 24 hours due to acute deterioration of liver function.
- Conditions
- Acute on Chronic Hepatic Failure, Acute Liver Failure, Liver Cirrhosis, Acute Alcoholic Hepatitis
- Being tested
- IDN-6556, Placebo
- Keywords
- Liver Failure, Cirrhosis, Alcoholic Hepatitis
- Medical subject headings
- Liver Failure, Acute, Liver Cirrhosis, Liver Failure, Fibrosis, Hepatitis, Alcoholic
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
PlaceboOther
| Study group | Role | What they receive |
|---|---|---|
| IDN-6556 5 mg | Experimental | Dosed twice daily Receives: Drug: IDN-6556 |
| IDN-6556 25 mg | Experimental | Dosed twice daily Receives: Drug: IDN-6556 |
| IDN-6556 50 mg | Experimental | Dosed twice daily Receives: Drug: IDN-6556 |
| Placebo | Placebo comparator | Dosed twice daily Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Curve (AUC)
Primary endpoints for AUC_0-8, AUC_0 last, AUC_0-inf on Day 1 and Day 4 for the active treatment arms were analyzed.
Measured: 28 days
Cmax
Primary endpoints forCmax on Day 1 and Day 4 for the active treatment arms were analyzed.
Measured: 28 Days
Tmax & t1/2 Parameters
Primary endpoints for tmax \& t1/2 on Day 1 and Day 4 for the active treatment arms were analyzed.
Measured: 28 Days
Secondary outcomes (3)
Levels of CK18/M30
Caspase-cleaved cytokeratin serum levels (CK18/M30)
Measured: Baseline, Day 2, Day 4, Day 7, Day 14, Day 21, and Day 28
Levels of CK18/M65
Caspase full-length cytokeratin serum levels CK18/M65
Measured: Baseline, Day 2, Day 4, Day 7, Day 14, Day 21, and Day 28
Levels of Caspase 3/7 RLU
Concentration of Caspase 3/7 Relative Light Units
Measured: Baseline, Day 2, Day 4, Day 7, Day 14, Day 21, and Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2013 (estimated)
- Study startSep 2013
- Primary completionJan 2015
- Study completionFeb 2015
Why it stopped: Data needs met
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 Acute on Chronic Hepatic FailureStudies 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Conatus Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Stephen Ryder, Dr., Principal investigator, Nottingham University Hospitals NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01937130
- Sponsor's protocol ID
- IDN-6556-02
- Status last verified
- Mar 2016
- First submitted
- 4 Sep 2013
- Last updated
- 11 Apr 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Placebo-Controlled, Multicenter, Double-Blind, Randomized, Pharmacokinetic and Pharmacodynamic Trial of IDN-6556 in Subjects With Acute-on-Chronic Liver Failure
- ClinicalTrials.gov ID
- NCT01937130
- Acronym / sponsor ID
- IDN-6556-02
- Conditions
- Acute on Chronic Hepatic Failure, Acute Liver Failure, Liver Cirrhosis, Acute Alcoholic Hepatitis
- Keywords
- Liver Failure, Cirrhosis, Alcoholic Hepatitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Data needs met
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Conatus Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Study start
- Sep 2013
- Primary completion
- Jan 2015 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 9 Sep 2013 (estimated)
- Results
- Posted 11 Apr 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study will evaluate the pharmacokinetics, pharmacodynamics, safety and preliminary efficacy of IDN-6556 in subjects with cirrhosis of the liver who are hospitalized for more than 24 hours due to acute deterioration of liver function.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| IDN-6556 5 mg | Experimental | Drug: IDN-6556Dosed twice daily |
| IDN-6556 25 mg | Experimental | Drug: IDN-6556Dosed twice daily |
| IDN-6556 50 mg | Experimental | Drug: IDN-6556Dosed twice daily |
| Placebo | Placebo comparator | Other: PlaceboDosed twice daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 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 understand and comply with the requirements of the study
- Subjects with a clinical, radiological and/or histological diagnosis of cirrhosis
- Subjects having not required hospital admission within 4 weeks of screening for a complication of cirrhosis
- Subjects with an acute deterioration of liver function
- Subjects who meet one of the following criteria:
Key exclusion criteria (11 listed)
- Known infection with HIV
- Subjects with cirrhosis who develop decompensation at any time in the postoperative period following partial hepatectomy
- Subjects with evidence of uncontrolled infection defined as persistent bacterial culture positivity despite adequate antibiotic therapy
- Subjects with clinical evidence of disseminated intravascular coagulation
- Subjects with chronic and/or pre-existing kidney disease defined as eGFR (estimated glomerular filtration rate) of less than 30 mL/min for 3 months or longer
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-03491390 | Drug | IDN-6556 25 mg, IDN-6556 5 mg, IDN-6556 50 mg |
| Placebo | Other | Placebo |
Primary outcome
Area Under the Curve (AUC)
Time frame: 28 days
Primary endpoints for AUC_0-8, AUC_0 last, AUC_0-inf on Day 1 and Day 4 for the active treatment arms were analyzed.
Cmax
Time frame: 28 Days
Primary endpoints forCmax on Day 1 and Day 4 for the active treatment arms were analyzed.
Tmax & t1/2 Parameters
Time frame: 28 Days
Primary endpoints for tmax \& t1/2 on Day 1 and Day 4 for the active treatment arms were analyzed.
3 secondary outcomes
Levels of CK18/M30
Time frame: Baseline, Day 2, Day 4, Day 7, Day 14, Day 21, and Day 28
Levels of CK18/M65
Time frame: Baseline, Day 2, Day 4, Day 7, Day 14, Day 21, and Day 28
Levels of Caspase 3/7 RLU
Time frame: Baseline, Day 2, Day 4, Day 7, Day 14, Day 21, and Day 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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RecruitingObservational study
CytOSorb TreatMent Of Critically Ill PatientS Registry
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Very Low-volume Plasma Exchange in ACLF
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A Novel Extracorporeal Liver Support Therapy In ALCF and to Evaluate the Efficacy of DIALIVE 2.0, a Liver Dialysis Device.
Acute-on-Chronic Liver Failure (ACLF), Liver Cirrhosis
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.
Stephen Ryder, Dr. principal investigator
Nottingham University Hospitals NHS Trust
26 sites in 2 countries: 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 Acute on Chronic Hepatic Failure and Acute Liver Failure, run by Conatus Pharmaceuticals Inc. at 26 sites in 2 countries.
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 10 inclusion and 11 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: stopped early, as of the sponsor's last update on 11 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in United Kingdom, 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 11 Apr 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?
Area Under the Curve (AUC) (time frame: 28 days). 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?
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 11 Apr 2016.