Clinical trial NCT01804829: Civacir® Polyclonal Immune Globulin (IgG) to Prevent Hepatitis C Virus (HCV) Recurrence in Liver Transplant Patients.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C Infection
Viruses
Hepatocellular Carcinoma
Hepatitis, Viral, Human
Liver Cirrhosis
Keywords: HCV Liver Transplant Immunoglobulin PCR SVR
Lead sponsor: Biotest Pharmaceuticals Corporation
Sponsor class: INDUSTRY
First posted: 2013-03-05
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Determine the efficacy of Civacir® in preventing post-transplant HCV recurrence at 22 weeks post transplant
timeFrame: 22 weeks
Secondary outcomes:
measure: Determine the efficacy of Civacir® in preventing post-transplant HCV recurrence at 4 and 34 weeks post transplant
timeFrame: 34 weeks
Other outcomes:
measure: Determine the biochemical response of Civacir® in preventing post-transplant HCV recurrence at 22 and 34 weeks post transplant
timeFrame: 34 weeks
measure: Evaluate the safety of Civacir® in preventing post-transplant HCV recurrence up to 34 weeks post transplant
timeFrame: 34 weeks
measure: Evaluate the pharmacokinetics of Civacir® up to 34 weeks post transplant
timeFrame: 34 weeks
Locations:
city: Los Angeles
country: United States
facility: University of Southern California / Keck Hospital
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Transplant Institute
state: Florida
city: Atlanta
country: United States
facility: Piedmont Hospital
state: Georgia
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Lexington
country: United States
facility: University of Kentucky Chandler Medical Center
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Hospital
state: Massachusetts
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: New York
country: United States
facility: The Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Columbia University College of Physicians and Surgeons
state: New York
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Memphis
country: United States
facility: Methodist University Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Houston
country: United States
facility: Advanced Liver Therapies / St. Luke's Episcopal Hospital
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Houston
country: United States
facility: Houston Methodist
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health Sciences Center
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
Study officials:
affiliation: University of California, San Francisco
name: Norah Terrault, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Everson GT, Terrault NA, Lok AS, Rodrigo del R, Brown RS Jr, Saab S, Shiffman ML, Al-Osaimi AM, Kulik LM, Gillespie BW, Everhart JE; Adult-to-Adult Living Donor Liver Transplantation Cohort Study. A randomized controlled trial of pretransplant antiviral therapy to prevent recurrence of hepatitis C after liver transplantation. Hepatology. 2013 May;57(5):1752-62. doi: 10.1002/hep.25976. Epub 2013 Jan 17.
citation: Davis GL, Nelson DR, Terrault N, Pruett TL, Schiano TD, Fletcher CV, Sapan CV, Riser LN, Li Y, Whitley RJ, Gnann JW Jr; Collaborative Antiviral Study Group. A randomized, open-label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients. Liver Transpl. 2005 Aug;11(8):941-9. doi: 10.1002/lt.20405.