Liver FibrosisPhase 2POLT-HCV-SVRNCT02138253
A Trial of IDN-6556 in Post Orthotopic Liver Transplant for Chronic HCV
A Phase 2 study testing IDN-6556 in people with Liver Fibrosis and Hepatic Fibrosis, run by Conatus Pharmaceuticals Inc. at 35 sites in United States.
Trial summary
This is a double-blind, multicenter study involving patients with chronic HCV infection who had a liver transplantation; developed HCV-related liver fibrosis and/or incomplete cirrhosis; achieved a sustained virologic response (SVR) following anti-HCV therapy; but still have fibrosis and/or incomplete cirrhosis on… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Fibrosis, Hepatic Fibrosis, Liver Cirrhosis
- What is being tested?
- IDN-6556
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 35 sitesUnited States
- Study dates
- May 2014to 9 Mar 2018
- 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
- History of orthotopic liver transplantation for HCV-induced liver disease
- Diagnosis of HCV infection (HCV-RNA detectable in serum) and liver fibrosis and/or incomplete cirrhosis status post liver transplantation, and achieved a sustained virologic response (SVR) with anti-viral HCV treatment within 18 months of Day 1
- Liver fibrosis on liver histology as read by central histopathologist of Ishak F2 to F6 within three months of Day 1 (Up to 15 subjects with an Ishak score of F6 can be enrolled)
- 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 hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV)
- History of renal transplant and/or severe renal impairment defined as eGFR (estimated glomerular filtration rate) of less than 30 mL/min/1.73 m2
- Evidence of tumor burden >Milan criteria, or evidence of micro- or macrovascular invasion in explanted liver
- Hepatocellular carcinoma (HCC) at entry into the study
- Concurrent sirolimus (rapamycin) use
- History or presence of clinically concerning cardiac arrhythmias, or prolongation of Screening (pre-treatment) QT or QTc interval of > 480 milliseconds (msec)
- Subjects with diagnosed or suspected systemic lupus erythematosus (SLE) and/or rheumatoid arthritis (RA)
- If female: known pregnancy, positive urine or serum pregnancy test, or lactating/breastfeeding
Trial locations and contacts
35 sites in 1 country.
35 sites in 1 country
United States35 sites
Piedmont Atlanta Hospital
Atlanta, Georgia, 30309
John Hopkins Hospital
Baltimore, Maryland, 21287
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Rush University Medical Center
Chicago, Illinois, 60612
University of Chicago Medicine
Chicago, Illinois, 60637
University of Cincinnati Physicians Company
Cincinnati, Ohio, 45267
Southern California Research Center
Coronado, California, 92118
Henery Ford Health System
Detroit, Michigan, 48202
Baylor All Saints Medical Center
Fort Worth, Texas, 76104
University of Florida
Gainesville, Florida, 32610
Liver Associates of Texas, PA
Houston, Texas, 77030
University of Texas Health Science Center at Houston
Houston, Texas, 77030
VAMC/Baylor College of Medicine
Houston, Texas, 77030
Indiana University
Indianapolis, Indiana, 46202
University of Kansas Medical Center
Kansas City, Kansas, 66160
Scripps Clinic
La Jolla, California, 92037
Loma Linda University Medical Center
Loma Linda, California, 92354
UCLA Pfleger Liver Institute
Los Angeles, California, 90095
University of Louisville
Louisville, Kentucky, 40202
University of Miami
Miami, Florida, 33136
Tulane Health Science Center
New Orleans, Louisiana, 70112
Ochsner Clinic
New Orleans, Louisiana, 70121
Columbia University Medical Center
New York, New York, 10032
Rutgers New Jersey Medical School
Newark, New Jersey, 07103
Bon Secours Mary Immaculate Hospital
Newport News, Virginia, 23602
University of Pennsylvania Milton Hershey Hospital
Philadelphia, Pennsylvania, 19104
Temple University Hospital
Philadelphia, Pennsylvania, 19140
Albert Einstein Medical Center
Philadelphia, Pennsylvania, 19141
Bon Secours St. Mary's Hospital of Richmond
Richmond, Virginia, 23226
McGuire DVAMC
Richmond, Virginia, 23249
University of Utah
Salt Lake City, Utah, 84132
University of Washington Harborview Medical Center
Seattle, Washington, 98104
Saint Louis University
St Louis, Missouri, 63104
Georgetown University Hospital
Washington D.C., District of Columbia, 20007
Johns Hopkins Sibley Memorial Hospital
Washington D.C., District of Columbia, 21287
About this study
Official title: A Multicenter, Double-Blind, Randomized Trial of IDN-6556 in Subjects Who Had Hepatitis C Virus (HCV) Reinfection and Liver Fibrosis Following Orthotopic Liver Transplantation for Chronic HCV Infection and Who Subsequently Achieved a Sustained Virologic Response Following Anti-HCV Therapy
This is a double-blind, multicenter study involving patients with chronic HCV infection who had a liver transplantation; developed HCV-related liver fibrosis and/or incomplete cirrhosis; achieved a sustained virologic response (SVR) following anti-HCV therapy; but still have fibrosis and/or incomplete cirrhosis on liver biopsy to see if treatment with IDN-6556 is better than placebo in reversing or stopping the progression of the damage to the new liver caused by HCV.
Read the detailed description
There are data to suggest that with eradication of the HCV virus, improvements in liver fibrosis can be seen in the post-transplant population. However, amelioration of inflammatory activity, and deceleration of fibrosis progression is a gradual process over the course of many years. This placebo-controlled study is designed to evaluate the effects of IDN-6556, compared to placebo, on markers of apoptosis and inflammation, and liver histology.
- Conditions
- Liver Fibrosis, Hepatic Fibrosis, Liver Cirrhosis, Hepatic Cirrhosis
- Being tested
- IDN-6556, Placebo
- Keywords
- liver transplant, hepatitis C, liver fibrosis, hepatic fibrosis, liver cirrhosis, hepatic cirrhosis
- Medical subject headings
- Liver Cirrhosis, Hepatitis C
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
PlaceboDrug
Placebo control
| Study group | Role | What they receive |
|---|---|---|
| IDN-6556 | Experimental | IDN-6556 25 mg BID 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.
Number of Participants With At Least a One Stage Reduction From Baseline in Ishak Fibrosis Score
At least a one stage reduction from baseline in Ishak Fibrosis Stage. Score F0 No fibrosis F1 Fibrous expansion of some portal areas, with or without short fibrous septa F2 Fibrous expansion of most portal areas, with or without short fibrous septa F3 Fibrous expansion of most portal areas, with occasional portal to portal bridging F4 Fibrous expansion of portal areas, with marked bridging (portal to portal as well as portal to central) F5 Marked bridging (portal to portal and/or portal to central) with occasional nodules (incomplete cirrhosis) F6 Cirrhosis probable or definite
Since the primary analysis used multiple imputation methodology, the numerator and denominator varied across 20 imputations.
Measured: 24 months
Secondary outcomes (11)
Number of Participants With At Least a One Stage Reduction From Baseline in Ishak Fibrosis Score (Observed Cases Only)
At least a one stage reduction from baseline in Ishak Fibrosis Stage. Score F0 No fibrosis F1 Fibrous expansion of some portal areas, with or without short fibrous septa F2 Fibrous expansion of most portal areas, with or without short fibrous septa F3 Fibrous expansion of most portal areas, with occasional portal to portal bridging F4 Fibrous expansion of portal areas, with marked bridging (portal to portal as well as portal to central) F5 Marked bridging (portal to portal and/or portal to central) with occasional nodules (incomplete cirrhosis) F6 Cirrhosis probable or definite
Measured: 24 months
Number of Participants With At Least a One Stage Reduction From Baseline in Ishak Fibrosis Score
At least a one stage reduction from baseline in Ishak Fibrosis Stage. Score F0 No fibrosis F1 Fibrous expansion of some portal areas, with or without short fibrous septa F2 Fibrous expansion of most portal areas, with or without short fibrous septa F3 Fibrous expansion of most portal areas, with occasional portal to portal bridging F4 Fibrous expansion of portal areas, with marked bridging (portal to portal as well as portal to central) F5 Marked bridging (portal to portal and/or portal to central) with occasional nodules (incomplete cirrhosis) F6 Cirrhosis probable or definite
Measured: 12 months
Alanine Aminotransferase (ALT) - Change From Baseline
Liver function laboratory parameter
Measured: Baseline and 24 months
Aspartate Aminotransferase (AST) Change From Baseline
Liver function laboratory parameter
Measured: Baseline and 24 months
Caspase 3/7 Change From Baseline
Mechanistic biomarker of liver function
Measured: Baseline and 24 months
cCK18/M30 Change From Baseline
Mechanistic biomarker of liver function.
Measured: Baseline and 24 months
flCK18/M65 Change From Baseline
Mechanistic biomarker of liver function
Measured: Baseline and 24 months
Ishak Modification of Knodell Histological Activity Index - Interface Hepatitis
The Ishak modification of Knodell histological activity index was determined by liver biopsy.
Interface hepatitis
- 0 = None
- 1 = Mild (local, few portal areas)
- 2 = Mild/moderate (focal, most portal areas)
- 3 = Moderate (continuous around <50% of tracts or septa)
- 4 = Severe (continuous around >50% of tracts or septa)
Measured: 24 months
Ishak Modification of Knodell Histological Index - Confluent Necrosis
The Ishak modification of Knodell histological activity index will be determined by liver biopsy. The four items and their categorizations scores include:
- confluent necrosis
- 0 = None
- 1 = Focal confluent necrosis
- 2 = Zone 3 necrosis in some areas
- 3 = Zone 3 necrosis in most areas
- 4 = Zone 3 necrosis + occasional portal-central bridging
- 5 = Zone 3 necrosis + multiple portal-central bridging
- 6 = Panacinar or multiacinar necrosis
Measured: 24 months
Ishak Modification of Knodell Histological Index - Parenchymal Injury
The Ishak modification of Knodell histological activity index will be determined by liver biopsy.
- parenchymal injury (focal lytic necrosis, apoptosis and focal inflammation)
- 0 = None
- 1 = One focus or less per 10× objective
- 2 = Two to four foci per 10× objective
- 3 = Five to ten foci per 10× objective
- 4 = More than ten foci per 10× objective
Measured: 24 months
Ishak Modification of Knodell Histological Index - Portal Inflammation
Portal inflammation
- 0 = None
- 1 = Mild, some or all portal areas
- 2 = Moderate, some or all portal areas
- 3 = Moderate/marked, all portal areas
- 4 = Marked, all portal areas
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2014 (estimated)
- Study startMay 2014
- Primary completion15 Feb 2018
- Study completion9 Mar 2018
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 FibrosisStudies 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
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Conatus Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- David Hagerty, MD, Study chair, Conatus Pharmaceuticals Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02138253
- Sponsor's protocol ID
- IDN-6556-07
- Acronym
- POLT-HCV-SVR
- Status last verified
- Nov 2019
- First submitted
- 12 May 2014
- Last updated
- 11 Dec 2019
- 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 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Double-Blind, Randomized Trial of IDN-6556 in Subjects Who Had Hepatitis C Virus (HCV) Reinfection and Liver Fibrosis Following Orthotopic Liver Transplantation for Chronic HCV Infection and Who Subsequently Achieved a Sustained Virologic Response Following Anti-HCV Therapy
- ClinicalTrials.gov ID
- NCT02138253
- Acronym / sponsor ID
- POLT-HCV-SVR / IDN-6556-07
- Conditions
- Liver Fibrosis, Hepatic Fibrosis, Liver Cirrhosis, Hepatic Cirrhosis
- Keywords
- liver transplant, hepatitis C, liver fibrosis, hepatic fibrosis, liver cirrhosis, hepatic cirrhosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Conatus Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Study start
- May 2014
- Primary completion
- 15 Feb 2018 (actual)
- Study completion
- 9 Mar 2018 (actual)
- First posted
- 14 May 2014 (estimated)
- Results
- Posted 11 Dec 2019
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 double-blind, multicenter study involving patients with chronic HCV infection who had a liver transplantation; developed HCV-related liver fibrosis and/or incomplete cirrhosis; achieved a sustained virologic response (SVR) following anti-HCV therapy; but still have fibrosis and/or incomplete cirrhosis on liver biopsy to see if treatment with IDN-6556 is better than placebo in reversing or stopping the progression of the damage to the new liver caused by HCV.
Detailed description
There are data to suggest that with eradication of the HCV virus, improvements in liver fibrosis can be seen in the post-transplant population. However, amelioration of inflammatory activity, and deceleration of fibrosis progression is a gradual process over the course of many years. This placebo-controlled study is designed to evaluate the effects of IDN-6556, compared to placebo, on markers of apoptosis and inflammation, and liver histology.
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-6556IDN-6556 25 mg BID |
| 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 (5 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
- History of orthotopic liver transplantation for HCV-induced liver disease
- Diagnosis of HCV infection (HCV-RNA detectable in serum) and liver fibrosis and/or incomplete cirrhosis status post liver transplantation, and achieved a sustained virologic response (SVR) with anti-viral HCV treatment within 18 months of Day 1
- Liver fibrosis on liver histology as read by central histopathologist of Ishak F2 to F6 within three months of Day 1 (Up to 15 subjects with an Ishak score of F6 can be enrolled)
- 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 (8 listed)
- Known infection with hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV)
- History of renal transplant and/or severe renal impairment defined as eGFR (estimated glomerular filtration rate) of less than 30 mL/min/1.73 m2
- Evidence of tumor burden >Milan criteria, or evidence of micro- or macrovascular invasion in explanted liver
- Hepatocellular carcinoma (HCC) at entry into the study
- Concurrent sirolimus (rapamycin) use
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 |
| PlaceboPlacebo control | Drug | Placebo |
Primary outcome
Number of Participants With At Least a One Stage Reduction From Baseline in Ishak Fibrosis Score
Time frame: 24 months
At least a one stage reduction from baseline in Ishak Fibrosis Stage. Score F0 No fibrosis F1 Fibrous expansion of some portal areas, with or without short fibrous septa F2 Fibrous expansion of most portal areas, with or without short fibrous septa F3 Fibrous expansion of most portal areas, with occasional portal to portal bridging F4 Fibrous expansion of portal areas, with marked bridging (portal to portal as well as portal to central) F5 Marked bridging (portal to portal and/or portal to central) with occasional nodules (incomplete cirrhosis) F6 Cirrhosis probable or definite Since the primary analysis used multiple imputation methodology, the numerator and denominator varied across 20 imputations.
11 secondary outcomes
Number of Participants With At Least a One Stage Reduction From Baseline in Ishak Fibrosis Score (Observed Cases Only)
Time frame: 24 months
Number of Participants With At Least a One Stage Reduction From Baseline in Ishak Fibrosis Score
Time frame: 12 months
Alanine Aminotransferase (ALT) - Change From Baseline
Time frame: Baseline and 24 months
Aspartate Aminotransferase (AST) Change From Baseline
Time frame: Baseline and 24 months
Caspase 3/7 Change From Baseline
Time frame: Baseline and 24 months
cCK18/M30 Change From Baseline
Time frame: Baseline and 24 months
flCK18/M65 Change From Baseline
Time frame: Baseline and 24 months
Ishak Modification of Knodell Histological Activity Index - Interface Hepatitis
Time frame: 24 months
Ishak Modification of Knodell Histological Index - Confluent Necrosis
Time frame: 24 months
Ishak Modification of Knodell Histological Index - Parenchymal Injury
Time frame: 24 months
Ishak Modification of Knodell Histological Index - Portal Inflammation
Time frame: 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
David Hagerty, MD study chair
Conatus Pharmaceuticals Inc.
35 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 Fibrosis and Hepatic Fibrosis, run by Conatus Pharmaceuticals Inc. at 35 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 5 inclusion and 8 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 11 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 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 11 Dec 2019). 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 Participants With At Least a One Stage Reduction From Baseline in Ishak Fibrosis Score (time frame: 24 months). 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 Dec 2019.