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A Trial of IDN-6556 in Post Orthotopic Liver Transplant for Chronic HCV (POLT-HCV-SVR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02138253
Recruitment Status : Completed
First Posted : May 14, 2014
Results First Posted : December 11, 2019
Last Update Posted : December 11, 2019
Sponsor:
Information provided by (Responsible Party):
Conatus Pharmaceuticals Inc.

Tracking Information
First Submitted Date  ICMJE May 12, 2014
First Posted Date  ICMJE May 14, 2014
Results First Submitted Date  ICMJE May 2, 2019
Results First Posted Date  ICMJE December 11, 2019
Last Update Posted Date December 11, 2019
Study Start Date  ICMJE May 2014
Actual Primary Completion Date February 15, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 21, 2019)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 13, 2014)
Ishak Fibrosis Score [ Time Frame: 24 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 21, 2019)
  • 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
  • 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
  • Alanine Aminotransferase (ALT) - Change From Baseline [ Time Frame: Baseline and 24 months ]
    Liver function laboratory parameter
  • Aspartate Aminotransferase (AST) Change From Baseline [ Time Frame: Baseline and 24 months ]
    Liver function laboratory parameter
  • Caspase 3/7 Change From Baseline [ Time Frame: Baseline and 24 months ]
    Mechanistic biomarker of liver function
  • cCK18/M30 Change From Baseline [ Time Frame: Baseline and 24 months ]
    Mechanistic biomarker of liver function.
  • flCK18/M65 Change From Baseline [ Time Frame: Baseline and 24 months ]
    Mechanistic biomarker of liver function
  • 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)
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: May 13, 2014)
Necro-inflammatory sub-score of the modified Histological Activity Index [ Time Frame: 24 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Trial of IDN-6556 in Post Orthotopic Liver Transplant for Chronic HCV
Official Title  ICMJE 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
Brief 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 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Liver Fibrosis
  • Hepatic Fibrosis
  • Liver Cirrhosis
  • Hepatic Cirrhosis
Intervention  ICMJE
  • Drug: IDN-6556
    Other Names:
    • emricasan
    • PF-03491390
  • Drug: Placebo
    Placebo control
Study Arms  ICMJE
  • Experimental: IDN-6556
    IDN-6556 25 mg BID
    Intervention: Drug: IDN-6556
  • Placebo Comparator: Placebo
    Placebo BID
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 9, 2018)
64
Original Estimated Enrollment  ICMJE
 (submitted: May 13, 2014)
60
Actual Study Completion Date  ICMJE March 9, 2018
Actual Primary Completion Date February 15, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02138253
Other Study ID Numbers  ICMJE IDN-6556-07
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Conatus Pharmaceuticals Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Conatus Pharmaceuticals Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: David Hagerty, MD Conatus Pharmaceuticals
PRS Account Conatus Pharmaceuticals Inc.
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP