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

Primary Purpose

Hepatitis C Infection, Viruses, Hepatocellular Carcinoma

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Civacir® 10%
Sponsored by
Biotest Pharmaceuticals Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Hepatitis C Infection focused on measuring HCV Liver Transplant Immunoglobulin PCR SVR

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Southern California / Keck Hospital
  • University of California San Francisco
  • University of Miami Miller School of Medicine
  • Florida Hospital Transplant Institute
  • Piedmont Hospital
  • Emory University School of Medicine
  • Northwestern Memorial Hospital
  • University of Kentucky Chandler Medical Center
  • Ochsner Medical Center
  • Beth Israel Deaconess Medical Center
  • Lahey Hospital
  • NYU Langone Medical Center
  • The Mount Sinai Medical Center
  • Columbia University College of Physicians and Surgeons
  • Oregon Health & Science University
  • Methodist University Hospital
  • Vanderbilt University Medical Center
  • Baylor University Medical Center
  • Advanced Liver Therapies / St. Luke's Episcopal Hospital
  • Houston Methodist Hospital
  • Houston Methodist
  • University of Utah Health Sciences Center
  • University of Virginia Health System

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

No Intervention

Experimental

Experimental

Arm Label

Observational Control

Civacir® 10% at 200 mg/kg dose

Civacir® 10% at 300 mg/kg dose

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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.

Full Information

First Posted
March 4, 2013
Last Updated
March 14, 2017
Sponsor
Biotest Pharmaceuticals Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT01804829
Brief Title
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

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
June 2013 (undefined)
Primary Completion Date
February 2016 (Actual)
Study Completion Date
June 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biotest Pharmaceuticals Corporation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C Infection, Viruses, Hepatocellular Carcinoma, Hepatitis, Viral, Human, Liver Cirrhosis
Keywords
HCV Liver Transplant Immunoglobulin PCR SVR

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
80 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Observational Control
Arm Type
No Intervention
Arm Description
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.
Arm Title
Civacir® 10% at 200 mg/kg dose
Arm Type
Experimental
Arm Description
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.
Arm Title
Civacir® 10% at 300 mg/kg dose
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Civacir® 10%
Other Intervention Name(s)
Civacir®, Hepatitis C Immune Globulin Intravenous (Human), human polyclonal immune globulin (IgG), HCIg
Intervention Description
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.
Primary Outcome Measure Information:
Title
Determine the efficacy of Civacir® in preventing post-transplant HCV recurrence at 22 weeks post transplant
Description
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).
Time Frame
22 weeks
Secondary Outcome Measure Information:
Title
Determine the efficacy of Civacir® in preventing post-transplant HCV recurrence at 4 and 34 weeks post transplant
Description
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.
Time Frame
34 weeks
Other Pre-specified Outcome Measures:
Title
Determine the biochemical response of Civacir® in preventing post-transplant HCV recurrence at 22 and 34 weeks post transplant
Description
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.
Time Frame
34 weeks
Title
Evaluate the safety of Civacir® in preventing post-transplant HCV recurrence up to 34 weeks post transplant
Description
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.
Time Frame
34 weeks
Title
Evaluate the pharmacokinetics of Civacir® up to 34 weeks post transplant
Description
Evaluate the pharmacokinetics of Civacir® following intravenous infusion(s).
Time Frame
34 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Norah Terrault, MD, MPH
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Southern California / Keck Hospital
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
University of Miami Miller School of Medicine
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Florida Hospital Transplant Institute
City
Orlando
State/Province
Florida
ZIP/Postal Code
32804
Country
United States
Facility Name
Piedmont Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30309
Country
United States
Facility Name
Emory University School of Medicine
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Northwestern Memorial Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Kentucky Chandler Medical Center
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
Ochsner Medical Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Lahey Hospital
City
Burlington
State/Province
Massachusetts
ZIP/Postal Code
01805
Country
United States
Facility Name
NYU Langone Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
The Mount Sinai Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Columbia University College of Physicians and Surgeons
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Methodist University Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38104
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Baylor University Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Advanced Liver Therapies / St. Luke's Episcopal Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Houston Methodist Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Houston Methodist
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Utah Health Sciences Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
University of Virginia Health System
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
22821361
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.
Results Reference
background
PubMed Identifier
16035063
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.
Results Reference
background

Learn more about this trial

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

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