Clinical trial NCT02138253: A Trial of IDN-6556 in Post Orthotopic Liver Transplant for Chronic HCV
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Liver Fibrosis
Hepatic Fibrosis
Liver Cirrhosis
Hepatic Cirrhosis
Keywords: liver transplant
hepatitis C
liver fibrosis
hepatic fibrosis
liver cirrhosis
hepatic cirrhosis
Lead sponsor: Conatus Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2014-05-14
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With At Least a One Stage Reduction From Baseline in Ishak Fibrosis Score
timeFrame: 24 months
Secondary outcomes:
measure: Number of Participants With At Least a One Stage Reduction From Baseline in Ishak Fibrosis Score (Observed Cases Only)
timeFrame: 24 months
measure: Number of Participants With At Least a One Stage Reduction From Baseline in Ishak Fibrosis Score
timeFrame: 12 months
measure: Alanine Aminotransferase (ALT) - Change From Baseline
timeFrame: Baseline and 24 months
measure: Aspartate Aminotransferase (AST) Change From Baseline
timeFrame: Baseline and 24 months
measure: Caspase 3/7 Change From Baseline
timeFrame: Baseline and 24 months
measure: cCK18/M30 Change From Baseline
timeFrame: Baseline and 24 months
measure: flCK18/M65 Change From Baseline
timeFrame: Baseline and 24 months
measure: Ishak Modification of Knodell Histological Activity Index - Interface Hepatitis
timeFrame: 24 months
measure: Ishak Modification of Knodell Histological Index - Confluent Necrosis
timeFrame: 24 months
measure: Ishak Modification of Knodell Histological Index - Parenchymal Injury
timeFrame: 24 months
measure: Ishak Modification of Knodell Histological Index - Portal Inflammation
timeFrame: 24 months
Other outcomes:
Locations:
city: Coronado
country: United States
facility: Southern California Research Center
state: California
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA Pfleger Liver Institute
state: California
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Washington
country: United States
facility: Johns Hopkins Sibley Memorial Hospital
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Piedmont Atlanta Hospital
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medicine
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: New Orleans
country: United States
facility: Tulane Health Science Center
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Clinic
state: Louisiana
city: Baltimore
country: United States
facility: John Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henery Ford Health System
state: Michigan
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Newark
country: United States
facility: Rutgers New Jersey Medical School
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Physicians Company
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania Milton Hershey Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Albert Einstein Medical Center
state: Pennsylvania
city: Fort Worth
country: United States
facility: Baylor All Saints Medical Center
state: Texas
city: Houston
country: United States
facility: Liver Associates of Texas, PA
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: Houston
country: United States
facility: VAMC/Baylor College of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Newport News
country: United States
facility: Bon Secours Mary Immaculate Hospital
state: Virginia
city: Richmond
country: United States
facility: Bon Secours St. Mary's Hospital of Richmond
state: Virginia
city: Richmond
country: United States
facility: McGuire DVAMC
state: Virginia
city: Seattle
country: United States
facility: University of Washington Harborview Medical Center
state: Washington
Study officials:
affiliation: Conatus Pharmaceuticals Inc.
name: David Hagerty, MD
role: STUDY_CHAIR
References: