Civacir® Polyclonal Immune Globulin (IgG) to Prevent Hepatitis C Virus (HCV) Recurrence in Liver Transplant Patients.

Phase 3

Completed

Conditions: Liver Cirrhosis
Viruses
Hepatitis, Viral, Human
Hepatitis C Infection
Hepatocellular Carcinoma

Interventions: Biological: Civacir® 10%

Registration Number: NCT01804829

Lead Sponsor: Biotest Pharmaceuticals Corporation

Brief Summary: The purpose of this study is to test the safety and efficacy of Civacir® to prevent the recurrence of Hepatitis C Virus (HCV) after liver transplant.

Detailed Description: Civacir® 10%, Hepatitis C Immune Globulin Intravenous (Human) is a high-titer human polyclonal immune globulin (IgG) containing a diversity of antibodies that target and bind the hepatitis C virus (HCV) to prevent infection. Subjects who reduce their viral load to less than 100 IU/ml HCV RNA through up to 24 weeks of antiviral therapy prior to liver transplant are enrolled in the study. There is no requirement to reach undetectable virus prior to transplant as the function of Civacir® is to neutralize any remaining virus in circulation.

Subjects randomized to Civacir® treatment arms receive study drug infusions starting on the day of liver transplant followed by 15 doses over a 10 week period to prevent the recurrence of quantifiable Hepatitis C Virus (HCV) after liver transplant. The study will evaluate dosing arms ranging from 200 mg/kg to 300 mg/kg compared to a control arm. For the primary endpoint, efficacy is defined as persistent viral load suppression maintaining HCV RNA levels below the lower limit of quantitation as determined by central laboratory Polymerase Chain Reaction (PCR) at 22 weeks post-liver transplant and then at 34 weeks post-liver transplant to demonstrate durability of effect.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 80

Inclusion Criteria

Written informed consent obtained prior to any study-specific assessments and within 3 months (reconsent) of orthotopic liver transplantation (OLT).
HCV Genotype 1 through 6 Infection.
Subjects in the beginning of a new antiviral therapy regimen (regardless of prior treatment failures) for up to and including 24 weeks prior to the day of OLT.
Most recent evidence within the last 4 weeks that HCV RNA is <100 IU/mL. Subjects may be randomized based on local lab HCV RNA.
Male and female subjects (age 18-80 years).
Subject weight under 250 pounds.
Stable patient in a condition which in the opinion of the investigator would permit safe participation in the study.

Exclusion Criteria

Re-transplantation due to viral recurrence.
Positive HIV or HBV test within 90 days prior to transplantation.
Most recent PCR test indicating HCV RNA ≥100 IU/mL within 4 weeks of OLT.
Subjects having received organs from HCV positive donors.
Serum creatinine level >2.5 times the upper limit of normal or advanced renal disease at screening.
Pregnancy or single contraceptive measure or lactation period (females only).
Known intolerance to immunoglobulins or comparable substances (e.g. vaccination reaction).
Known absolute Immunoglobulin A (IgA) deficiency.
Known intolerance to proteins of human origin.
Participation in another clinical trial within 90 days before signing Informed Consent Form (ICF) or during the study (observational/ non-interventional and 988 studies allowed), and/or previous participation in 988 study (except for Study 988 screen failures).
Active drug and/or alcohol abuse.
Inability or lacking motivation to participate in the study.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Civacir® 10% at 200 mg/kg dose	Civacir® 10%	Subjects who attain HCV RNA \<100 IU/ml and are randomized to the Civacir 200 mg/kg treatment arm will receive Civacir® before liver transplant, followed by 15 infusions over a 10 week regimen, with standard post-transplant immunosuppressant therapy. Civacir® treated subjects will be followed up to 34 weeks post-transplant.
Civacir® 10% at 300 mg/kg dose	Civacir® 10%	Subjects who attain HCV RNA \<100 IU/ml and are randomized to the Civacir® 300 mg/kg treatment arm will receive Civacir® before liver transplant, followed by 15 infusions over a 10 week regimen, with standard post-transplant immunosuppressant therapy. Civacir® treated subjects will be followed up to 34 weeks post-transplant.

Primary Outcome Measures

Name	Time	Method
Determine the efficacy of Civacir® in preventing post-transplant HCV recurrence at 22 weeks post transplant	22 weeks	The primary objective is to assess the effect of administering Civacir® anti-HCV immunoglobulin therapy on prevention of orthotopic liver transplant (OLT) HCV recurrence, as measured by the proportion of subjects with unquantifiable HCV RNA levels at 22 weeks post-OLT, compared to the control group (not treated with Civacir® and considered standard of care).

Secondary Outcome Measures

Name	Time	Method
Determine the efficacy of Civacir® in preventing post-transplant HCV recurrence at 4 and 34 weeks post transplant	34 weeks	Evaluate the proportion of subjects with unquantifiable HCV RNA, as measured quantitatively by PCR at 4 and 34 weeks post-OLT, for assessing the durability of effect.

Trial Locations

Locations (23): Florida Hospital Transplant Institute
🇺🇸
Orlando, Florida, United States
Columbia University College of Physicians and Surgeons
🇺🇸
New York, New York, United States
Ochsner Medical Center
🇺🇸
New Orleans, Louisiana, United States
Vanderbilt University Medical Center
🇺🇸
Nashville, Tennessee, United States
University of Kentucky Chandler Medical Center
🇺🇸
Lexington, Kentucky, United States
University of Utah Health Sciences Center
🇺🇸
Salt Lake City, Utah, United States
University of Virginia Health System
🇺🇸
Charlottesville, Virginia, United States
University of Southern California / Keck Hospital
🇺🇸
Los Angeles, California, United States
University of Miami Miller School of Medicine
🇺🇸
Miami, Florida, United States
Emory University School of Medicine
🇺🇸
Atlanta, Georgia, United States
Northwestern Memorial Hospital
🇺🇸
Chicago, Illinois, United States
Beth Israel Deaconess Medical Center
🇺🇸
Boston, Massachusetts, United States
Lahey Hospital
🇺🇸
Burlington, Massachusetts, United States
Houston Methodist Hospital
🇺🇸
Houston, Texas, United States
Houston Methodist
🇺🇸
Houston, Texas, United States
University of California San Francisco
🇺🇸
San Francisco, California, United States
Piedmont Hospital
🇺🇸
Atlanta, Georgia, United States
The Mount Sinai Medical Center
🇺🇸
New York, New York, United States
Oregon Health & Science University
🇺🇸
Portland, Oregon, United States
Baylor University Medical Center
🇺🇸
Dallas, Texas, United States
Advanced Liver Therapies / St. Luke's Episcopal Hospital
🇺🇸
Houston, Texas, United States
NYU Langone Medical Center
🇺🇸
New York, New York, United States
Methodist University Hospital
🇺🇸
Memphis, Tennessee, United States