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

Study Overview
=================
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.

Official Title
-----------------
A Multi-Center, Randomized, Prospective, Open-Label Phase III Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Hepatitis C Immune Globulin Intravenous (Human), Civacir®, in Orthotopic Liver Transplant Recipients

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

Intervention / Treatment
-----------------
* Biological: Civacir® 10%


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Observational Control<br>Subjects who attain HCV RNA <100 IU/ml and are randomized to the control arm will receive standard post-transplant immunosuppressant therapy and be followed for a 34 week period. | |
| Experimental: Civacir® 10% at 200 mg/kg dose<br>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. | Biological: Civacir® 10%<br>* The active ingredient is Human Immunoglobulin G (IgG) which is a normal constituent purified from human source plasma containing a diversity of antibodies targeting the Hepatitis C Virus.<br>* Other names: HCIg;|
| Experimental: Civacir® 10% at 300 mg/kg dose<br>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. | Biological: Civacir® 10%<br>* The active ingredient is Human Immunoglobulin G (IgG) which is a normal constituent purified from human source plasma containing a diversity of antibodies targeting the Hepatitis C Virus.<br>* Other names: HCIg;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the efficacy of Civacir® in preventing post-transplant HCV recurrence at 22 weeks post transplant | 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). | 22 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the efficacy of Civacir® in preventing post-transplant HCV recurrence at 4 and 34 weeks post transplant | 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. | 34 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HCV Liver Transplant Immunoglobulin PCR SVR