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

Hepatocellular Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01804829
• Other study ID #: 988
• Status: Completed
• Phase: Phase 3
• First received: March 4, 2013
• Last updated: March 14, 2017
• Start date: June 2013
• Est. completion date: June 2016

Study information

• Verified date: March 2017
• Source: Biotest Pharmaceuticals Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: June 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C Infection
• Hepatitis, Viral, Human
• Hepatocellular Carcinoma
• Liver Cirrhosis
• Viruses

Intervention

Biological:
• Civacir® 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.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Biotest Pharmaceuticals Corporation

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Determine the biochemical response of Civacir® in preventing post-transplant HCV recurrence at 22 and 34 weeks post transplant	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.	34 weeks
Other	Evaluate the safety of Civacir® in preventing post-transplant HCV recurrence up to 34 weeks post transplant	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.	34 weeks
Other	Evaluate the pharmacokinetics of Civacir® up to 34 weeks post transplant	Evaluate the pharmacokinetics of Civacir® following intravenous infusion(s).	34 weeks
Primary	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	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

External Links

•   Biotest Pharmaceuticals Hepatitis C Immune Globulin (HCIG)