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

Liver Cirrhosis Clinical Trial

— POLT-HCV-SVR  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02138253
• Other study ID #: IDN-6556-07
• Status: Completed
• Phase: Phase 2
• Start date: May 2014
• Est. completion date: March 9, 2018

Study information

• Verified date: November 2019
• Source: Conatus Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: March 9, 2018
• Est. primary completion date: February 15, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Fibrosis
• Hepatic Cirrhosis
• Hepatic Fibrosis
• Liver Cirrhosis
• Liver Fibrosis

Intervention

Drug:
• IDN-6556

• Placebo
Placebo control

Locations

Country	Name	City	State
United States	Piedmont Atlanta Hospital	Atlanta	Georgia
United States	John Hopkins Hospital	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago Medicine	Chicago	Illinois
United States	University of Cincinnati Physicians Company	Cincinnati	Ohio
United States	Southern California Research Center	Coronado	California
United States	Henery Ford Health System	Detroit	Michigan
United States	Baylor All Saints Medical Center	Fort Worth	Texas
United States	University of Florida	Gainesville	Florida
United States	Liver Associates of Texas, PA	Houston	Texas
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	VAMC/Baylor College of Medicine	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Scripps Clinic	La Jolla	California
United States	Loma Linda University Medical Center	Loma Linda	California
United States	UCLA Pfleger Liver Institute	Los Angeles	California
United States	University of Louisville	Louisville	Kentucky
United States	University of Miami	Miami	Florida
United States	Ochsner Clinic	New Orleans	Louisiana
United States	Tulane Health Science Center	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	Rutgers New Jersey Medical School	Newark	New Jersey
United States	Bon Secours Mary Immaculate Hospital	Newport News	Virginia
United States	Albert Einstein Medical Center	Philadelphia	Pennsylvania
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania Milton Hershey Hospital	Philadelphia	Pennsylvania
United States	Bon Secours St. Mary's Hospital of Richmond	Richmond	Virginia
United States	McGuire DVAMC	Richmond	Virginia
United States	Saint Louis University	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	University of Washington Harborview Medical Center	Seattle	Washington
United States	Georgetown University Hospital	Washington	District of Columbia
United States	Johns Hopkins Sibley Memorial Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Conatus Pharmaceuticals Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	24 months
Secondary	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	24 months
Secondary	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	12 months
Secondary	Alanine Aminotransferase (ALT) - Change From Baseline	Liver function laboratory parameter	Baseline and 24 months
Secondary	Aspartate Aminotransferase (AST) Change From Baseline	Liver function laboratory parameter	Baseline and 24 months
Secondary	Caspase 3/7 Change From Baseline	Mechanistic biomarker of liver function	Baseline and 24 months
Secondary	cCK18/M30 Change From Baseline	Mechanistic biomarker of liver function.	Baseline and 24 months
Secondary	flCK18/M65 Change From Baseline	Mechanistic biomarker of liver function	Baseline and 24 months
Secondary	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)	24 months
Secondary	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	24 months
Secondary	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	24 months
Secondary	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	24 months