Truvada Versus Truvada Plus Hepatitis B Immunoglobulin (HBIg) in Prevention of Chronic Hepatitis B Recurrence Post Liver Transplant
Condition: Chronic Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic; Recurrence
Intervention: FTC/TDF; Hepatitis B Immunoglobulin (HBIg)
Intervention description: Emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg was administered as a fixed-dose combination tablet orally once daily.; HBIg was administered either intravenously or by intramuscular injection at a dose and frequency as prescribed by the investigative site protocol.
Intervention MeSH terms: Immunoglobulins; Immunoglobulins, Intravenous; Antibodies
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Truvada; HBIg; Chronic Hepatitis B Recurrence; Post Orthotopic Liver Transplant

Summary:

      The objective of this 96-week study was to evaluate the safety and antiviral efficacy of
      emtricitabine/tenofovir disoproxil fumarate (FTC/TDF, coformulated; Truvada®) with or without
      hepatitis B immunoglobulin (HBIg) in preventing the recurrence of chronic hepatitis B
      following liver transplantation, in participants who were chronically infected with hepatitis
      B prior to transplantation.

      Prior to enrollment, participants were required to have received at least 12 weeks of HBIg
      therapy following liver transplantation. Enrolled participants then received FTC/TDF plus
      HBIg for an initial 24-week pre-randomization treatment period. Participants who completed
      the pre-randomization period and who achieved sustained viral suppression were randomized to
      continue treatment with FTC/TDF with or without HBIg for an additional 72 weeks (randomized
      period). The antiviral efficacy of treatment was assessed by measuring hepatitis B virus
      levels in the blood (HBV DNA). Safety and tolerability was monitored by assessing adverse
      events and various laboratory parameters.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult subjects (18-75 years of age) with either hepatitis e antigen (HBeAg) positive
             or HBeAg negative chronic HBV prior to transplant

          -  Willing and able to provide written informed consent

          -  Subjects with detectable antibody to hepatitis B surface antigen performed by a local
             laboratory result within 30 days of screening

          -  Subjects must have been stable and may not have had 2 or more of the following
             laboratory parameters associated with decompensated liver disease: conjugated
             bilirubin > 1.5 x the upper limit of the normal range (ULN), prothrombin time > 1.5 x
             ULN, platelets < 60,000/mm^3, serum albumin < 3.0 g/dL

          -  Must have had at least 12 weeks of center-specific prophylactic therapy including
             hepatitis B immunoglobulin (HBIg) posttransplant

          -  Calculated creatinine clearance ≥ 40 mL/min using the Cockcroft-Gault equation

          -  No significant evidence of ongoing deterioration of renal function

          -  Negative serum beta-human chorionic gonadotropin (for females of childbearing
             potential only)

        Exclusion Criteria:

          -  Subjects with HBV recurrence, ie, confirmed HBV DNA ≥ 400 copies/mL, following liver
             transplant

          -  Pregnant women, women who were breast feeding or who believed they may have wished to
             become pregnant during the course of the study

          -  Males and females of reproductive potential who were unwilling to use an effective
             method of contraception during the study and for at least 30 days from the date of
             last dose of study drug

          -  Evidence of hepatocellular carcinoma (HCC), eg, alpha-fetoprotein > 50 ng/mL, or by
             any other standard of care measure or presence of multifocal HCC at the time of
             transplantation if transplantation was within 144 weeks of screening

          -  Prior TDF or FTC/TDF experience post-transplant or > 12 months treatment with TDF or
             FTC/TDF treatment pretransplant

          -  Coinfection with hepatitis C virus (by serology), HIV, or hepatitis D virus
             pretransplant or at screening

          -  Significant renal, cardiovascular, pulmonary, or neurological disease

          -  Known hypersensitivity to the study drugs, the metabolites, or formulation excipients

          -  Were likely to receive systemic drugs with nephrotoxic potential, except
             immunosuppressive agents (eg, cyclosporine, tacrolimus), during the course of the
             study

          -  History of variceal bleeding or hepatic encephalopathy following orthotopic liver
             transplantation