Randomized Phase II Study of Hepatitis C Immune Globulin Intravenous (Human), Civacir(TM), in Liver Transplantation
Condition: Sequelae of Viral Hepatitis; Transplantation Infection; Evidence of Liver Transplantation
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis
Intervention: Hepatitis C Immune Globulin Intravenous (Human) 5%
Intervention description: Hepatitis C Immune Globulin Intravenous (Human) 5%, [Civacir]: 18 infusions total, per schedule, of 300 or 400 mg/kg of body weight given with standard post-transplant therapy inclusive of immunosuppressive agents.
Intervention MeSH terms: Immunoglobulins; Antibodies; gamma-Globulins; Immunoglobulins, Intravenous; Rho(D) Immune Globulin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: hepatitis C; liver transplantation; immune globulin

Summary:

      A Phase 2 study to evaluate safety, pharmacokinetics and efficacy of Hepatitis C Immune
      Globulin Intravenous (human) [Civacir(TM)] for preventing or reducing the impact of recurrent
      HCV infection following liver transplantation.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female, 18 to 75 years of age.

          -  Written informed consent.

          -  Expectation of compliance with the protocol procedures.

          -  If female, have a negative pregnancy test within 3 days prior to randomization and use
             an acceptable method of contraception or be at least one year post-menopausal or
             surgically sterile.

          -  HCV infection identified by positive, quantifiable HCV-RNA test within 3 months prior
             to transplantation.

          -  First time liver transplant recipient.

          -  Primary, single organ recipient (deceased donor <65 years of age).

          -  Normal TSH.

          -  Subjects with a pre-LT diagnosis of hepatocellular carcinoma (HCC) may be enrolled
             provided: there is no evidence of extrahepatic spread, tumor is solitary and <5cm or
             there are up to three tumors <3 cm.

          -  Agree to receive study medication as outlined in the protocol and follow all study
             related procedures until the conclusion of their protocol participation.

          -  Agree to consume no alcohol during the entire study period.

        Exclusion Criteria:

          -  Has received an investigational agent within the last six weeks prior to liver
             transplantation. Exceptions include Theraspheres for hepatocellular carcinoma or
             rifaximin.

          -  Known immunoglobulin A deficiency.

          -  Subject weighs more than 112.5 Kg (248 pounds).

          -  Known history of cancer, suspected cancer, or cancer therapy within 12 months prior to
             the administration of the investigational product, except for treatment for basal cell
             carcinoma, squamous cell carcinoma, cancer of the cervix in situ, early stage prostate
             cancer (Gleason's grade 1 or 2), or a history of malignancy where the risk of
             recurrence is >= 20% within 2 years. A significant exception is hepatocellular
             carcinoma with predefined acceptability (see inclusion criteria).

          -  Has any condition judged by the study physician to preclude participation in the
             study, including any psychological disorder, which might hinder compliance.

          -  History of use of immunosuppressive or immunomodulatory drugs within 3 months prior to
             randomization (except low-dose physiologic replacement glucocorticoid therapy (<=10 mg
             of prednisone or equivalent per day).

          -  Recipient of liver from a living donor.

          -  Subjects whose liver is obtained from a non-beating heart donor.

          -  Subjects scheduled to receive a split liver transplantation.

          -  Liver transplants that were obtained from donors across ABO incompatible blood type.

          -  Donor liver cold ischemic time greater than 20 hours.

          -  Donor liver is from a hepatitis C positive donor.

          -  Evidence of any other unresolved infection and any unresolved opportunistic infection
             requiring treatment.

          -  Serum creatinine level >2.0 times the upper limit of normal or advanced renal disease
             at screening.

          -  Neutrophil count <1500 cells/mm3, WBC>20,000 x 109/L, Hgb <8 g/dL, or platelet count
             <25,000 cells/mm3.

          -  Planned use of T-cell depleting antibody therapies.

          -  Hepatitis B (sAg, cAb IgM), hepatitis A (IgM) or HIV infection.

          -  History of autoimmune disease (SLE, scleroderma, RA, etc.).

          -  Women who are pregnant or breast feeding.

          -  The use of colony stimulating factor agents to facilitate subject's entry into study
             within 2 weeks of enrollment.

          -  History of severe psychiatric disease, especially depression.

          -  Seizure disorders uncontrolled by anticonvulsants (within the last 12 mos).

          -  History of severe cardiac disease, unhealed gastric or duodenal ulcer, or other
             significant medical disease that would put the subject at risk from the volume of the
             infusions or significant risk of bleeding from the underlying condition.

          -  Evidence of alcohol and/or drug abuse within 6 months of entry or
             inability/unwilling-ness to abstain from alcohol throughout entire course of treatment
             and follow-up.

          -  Concomitant medication with rifabutin, pyrazinamide, isoniazid, thalidomide,
             oxymetholone (Anadrol).

          -  History of thyroid disease poorly controlled on prescribed medications.

          -  History or other evidence of severe illness or any other conditions which would make
             the subject, in the opinion of the investigator, unsuitable for Civacir treatment.