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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Biotest Pharmaceuticals Corporation
Sponsor:
Information provided by (Responsible Party):
Biotest Pharmaceuticals Corporation
ClinicalTrials.gov Identifier:
NCT01804829
First received: March 4, 2013
Last updated: June 17, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Hepatitis C Infection
Viruses
Hepatocellular Carcinoma
Hepatitis, Viral, Human
Liver Cirrhosis
Biological: Civacir® 10%
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by Biotest Pharmaceuticals Corporation:

Primary Outcome Measures:
  • Determine the efficacy of Civacir® in preventing post-transplant HCV recurrence at 22 weeks post transplant [ Time Frame: 22 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 34 weeks ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Determine the biochemical response of Civacir® in preventing post-transplant HCV recurrence at 22 and 34 weeks post transplant [ Time Frame: 34 weeks ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 34 weeks ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 34 weeks ] [ Designated as safety issue: No ]
    Evaluate the pharmacokinetics of Civacir® following intravenous infusion(s).


Estimated Enrollment: 90
Study Start Date: June 2013
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Observational Control
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
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%
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.
Other Names:
  • Civacir®
  • Hepatitis C Immune Globulin Intravenous (Human)
  • human polyclonal immune globulin (IgG)
  • HCIg
Experimental: Civacir® 10% at 300 mg/kg dose
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%
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.
Other Names:
  • Civacir®
  • Hepatitis C Immune Globulin Intravenous (Human)
  • human polyclonal immune globulin (IgG)
  • HCIg

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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01804829

Contacts
Contact: Greg Osgood 561-989-5813 gosgood@biotestpharma.com
Contact: Christopher Dougherty, PhD, MS 561-989-5754 cdougherty@biotestpharma.com

Locations
United States, California
University of Southern California / Keck Hospital Recruiting
Los Angeles, California, United States, 90033
Principal Investigator: Linda Sher, M.D.         
University of California San Francisco Recruiting
San Francisco, California, United States, 94143
Principal Investigator: Norah Terrault, MD, MPH         
United States, Florida
University of Miami Miller School of Medicine Recruiting
Miami, Florida, United States, 33136
Principal Investigator: Kaylan Bhamidimarri, M.D., MPH         
Florida Hospital Transplant Institute Recruiting
Orlando, Florida, United States, 32804
Principal Investigator: Girihgar Vedula, MD         
United States, Georgia
Piedmont Atlanta Recruiting
Atlanta, Georgia, United States, 30309
Principal Investigator: Roshan Shrestha, MD         
United States, Illinois
Northwestern Memorial Hospital Recruiting
Chicago, Illinois, United States, 60611
Principal Investigator: Laura Kulik, MD         
United States, Kentucky
University of Kentucky Chandler Medical Center Recruiting
Lexington, Kentucky, United States, 40536
Principal Investigator: Jens Rosenau, MD         
United States, Louisiana
Ochsner Medical Center Recruiting
New Orleans, Louisiana, United States, 70121
Principal Investigator: George Therapondos, MD         
United States, Massachusetts
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Principal Investigator: Gerond Lake-Bakaar, MD         
Lahey Hospital Recruiting
Burlington, Massachusetts, United States, 01805
Principal Investigator: Fredric Gordan, MD         
United States, New York
The Mount Sinai Medical Center Recruiting
New York, New York, United States, 10029
Principal Investigator: Thomas D Schiano, MD         
Columbia University College of Physicians and Surgeons Recruiting
New York, New York, United States, 10032
Principal Investigator: Elizabeth Verna, MD, MS         
NYU Langone Medical Center Recruiting
New York, New York, United States, 10016
Principal Investigator: Lewis Teperman, MD         
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Principal Investigator: Joseph Ahn, MD         
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Principal Investigator: Michael Porayko, MD         
United States, Texas
Baylor University Medical Center Recruiting
Dallas, Texas, United States, 75246
Principal Investigator: Jacqueline O'Leary, MD         
Advanced Liver Therapies / St. Luke's Episcopal Hospital Recruiting
Houston, Texas, United States, 77030
Principal Investigator: John M Vierling, MD, FACP         
Sub-Investigator: Norman L Sussman, M.D.         
Houston Methodist Recruiting
Houston, Texas, United States, 77030
Principal Investigator: David Victor, MD         
United States, Utah
University of Utah Health Sciences Center Recruiting
Salt Lake City, Utah, United States, 84112
Principal Investigator: Jeffrey Campsen, M.D., FACS         
United States, Virginia
University of Virginia Health System Recruiting
Charlottesville, Virginia, United States, 22908
Principal Investigator: Daniel G Maluf, M.D.         
Sponsors and Collaborators
Biotest Pharmaceuticals Corporation
Investigators
Principal Investigator: Norah Terrault, MD, MPH University of California, San Francisco
  More Information

Additional Information:
Publications:
Responsible Party: Biotest Pharmaceuticals Corporation
ClinicalTrials.gov Identifier: NCT01804829     History of Changes
Other Study ID Numbers: 988
Study First Received: March 4, 2013
Last Updated: June 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Biotest Pharmaceuticals Corporation:
HCV Liver Transplant Immunoglobulin PCR SVR

Additional relevant MeSH terms:
Hepatitis, Viral, Human
Hepatitis
Hepatitis A
Hepatitis C
Carcinoma, Hepatocellular
Liver Cirrhosis
Liver Diseases
Digestive System Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Immunoglobulins
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Antibodies
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014