Hepatitis C Infection, Hepatitis, Viral, Human, Hepatocellular Carcinoma, Liver Cirrhosis, Viruses
Conditions
Keywords
HCV Liver Transplant Immunoglobulin PCR SVR
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.
Interventions
BIOLOGICALCivacir® 10%
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.
Sponsors
Biotest Pharmaceuticals Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Determine the biochemical response of Civacir® in preventing post-transplant HCV recurrence at 22 and 34 weeks post transplant | 34 weeks | Evaluate the biochemical response at 22 and 34 weeks post-transplant: the proportions of subjects with normal ALT, AST, total bilirubin and alkaline phosphates at 22 and 34 weeks. |
| Evaluate the safety of Civacir® in preventing post-transplant HCV recurrence up to 34 weeks post transplant | 34 weeks | Evaluate the safety of Civacir® in the treatment of subjects with HCV undergoing liver transplantation by the number of adverse events including safety laboratory parameters. |
| Evaluate the pharmacokinetics of Civacir® up to 34 weeks post transplant | 34 weeks | Evaluate the pharmacokinetics of Civacir® following intravenous infusion(s). |
Countries
United States
Outcome results
None listed