Skip to main content
OpenTrials
Completed

NCT Number: NCT02138253

A Trial of IDN-6556 in Post Orthotopic Liver Transplant for Chronic HCV

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Liver Fibrosis Blood-Borne Infections Communicable Diseases Digestive System Diseases Fibrosis Flaviviridae Infections Hepatic Cirrhosis Hepatic Fibrosis Hepatitis Hepatitis C Hepatitis, Viral, Human Infections Liver Cirrhosis Liver Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms RNA Virus Infections Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Southern California Research Center, Coronado, California, United States

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Treatment and study plan

IDN-6556

Drug

Other names: emricasan, PF-03491390

Placebo

Drug

Placebo control

Primary outcomes

  1. 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.

Secondary outcomes

  1. Number of Participants With At Least a One Stage Reduction From Baseline in Ishak Fibrosis Score (Observed Cases Only)

    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

  2. Number of Participants With At Least a One Stage Reduction From Baseline in Ishak Fibrosis Score

    Time frame: 12 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

  3. Alanine Aminotransferase (ALT) - Change From Baseline

    Time frame: Baseline and 24 months

    Liver function laboratory parameter

  4. Aspartate Aminotransferase (AST) Change From Baseline

    Time frame: Baseline and 24 months

    Liver function laboratory parameter

  5. Caspase 3/7 Change From Baseline

    Time frame: Baseline and 24 months

    Mechanistic biomarker of liver function

  6. cCK18/M30 Change From Baseline

    Time frame: Baseline and 24 months

    Mechanistic biomarker of liver function.

  7. flCK18/M65 Change From Baseline

    Time frame: Baseline and 24 months

    Mechanistic biomarker of liver function

  8. Ishak Modification of Knodell Histological Activity Index - Interface Hepatitis

    Time frame: 24 months

    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)

  9. Ishak Modification of Knodell Histological Index - Confluent Necrosis

    Time frame: 24 months

    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

  10. Ishak Modification of Knodell Histological Index - Parenchymal Injury

    Time frame: 24 months

    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

  11. Ishak Modification of Knodell Histological Index - Portal Inflammation

    Time frame: 24 months

    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

Sponsors and collaborators

Lead sponsor

Conatus Pharmaceuticals Inc.

Industry

Registry information

Official study 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

Acronym: POLT-HCV-SVR

Important dates

Study start
2014
Primary completion
2018
Study completion
2018
First posted
May 14, 2014
Registry last updated
Dec 11, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.